Sample records for nasal vaccine delivery

  1. Stable Dry Powder Formulation for Nasal Delivery of Anthrax Vaccine

    PubMed Central

    Wang, Sheena H.; Kirwan, Shaun M.; Abraham, Soman N.; Staats, Herman F.; Hickey, Anthony J.

    2013-01-01

    There is a current biodefense interest in protection against Anthrax. Here we developed a new generation of stable and effective anthrax vaccine. We studied the immune response elicited by rPA delivered intranasally with a novel mucosal adjuvant, a mast cell activator Compound 48/80. The vaccine formulation was prepared in a powder form by spray-freeze-drying (SFD) under optimized conditions to produce particles with a target size of D50=25μm, suitable for delivery to the rabbit nasal cavity. Physicochemical properties of the powder vaccines were characterized to assess their delivery and storage potential. Structural stability of rPA was confirmed by CD and ATR-FTIR, while functional stability of rPA and C48/80 was monitored by cell-based assays. Animal study was performed using a unitdose powder device for direct nasal application. Results showed that C48/80 provided effective mucosal adjuvant activity in rabbits. Freshly prepared SFD powder vaccine formulations or powders stored for over two years at room temperature elicited significantly elevated serum PA-specific and lethal toxin neutralization antibody titers that were comparable to that induced by IM immunization with rPA. Nasal delivery of this vaccine formulation may be a viable alternative to the currently licensed vaccine, or an attractive vaccine platform for other mucosally transmitted diseases. PMID:21905034

  2. Stable dry powder formulation for nasal delivery of anthrax vaccine.

    PubMed

    Wang, Sheena H; Kirwan, Shaun M; Abraham, Soman N; Staats, Herman F; Hickey, Anthony J

    2012-01-01

    There is a current biodefense interest in protection against anthrax. Here, we developed a new generation of stable and effective anthrax vaccine. We studied the immune response elicited by recombinant protective antigen (rPA) delivered intranasally with a novel mucosal adjuvant, a mast cell activator compound 48/80 (C48/80). The vaccine formulation was prepared in a powder form by spray-freeze-drying (SFD) under optimized conditions to produce particles with a target size of D(50) = 25 μm, suitable for delivery to the rabbit nasal cavity. Physicochemical properties of the powder vaccines were characterized to assess their delivery and storage potential. Structural stability of rPA was confirmed by circular dichroism and attenuated total reflectance-Fourier transform infrared spectroscopy, whereas functional stability of rPA and C48/80 was monitored by cell-based assays. Animal study was performed using a unit-dose powder device for direct nasal application. Results showed that C48/80 provided effective mucosal adjuvant activity in rabbits. Freshly prepared SFD powder vaccine formulations or powders stored for over 2 years at room temperature elicited significantly elevated serum PA-specific and lethal toxin neutralization antibody titers that were comparable to that induced by intramuscular immunization with rPA. Nasal delivery of this vaccine formulation may be a viable alternative to the currently licensed vaccine or an attractive vaccine platform for other mucosally transmitted diseases. Copyright © 2011 Wiley-Liss, Inc.

  3. Formulation of a dry powder influenza vaccine for nasal delivery.

    PubMed

    Garmise, Robert J; Mar, Kevin; Crowder, Timothy M; Hwang, C Robin; Ferriter, Matthew; Huang, Juan; Mikszta, John A; Sullivan, Vincent J; Hickey, Anthony J

    2006-03-10

    The purpose of this research was to prepare a dry powder vaccine formulation containing whole inactivated influenza virus (WIIV) and a mucoadhesive compound suitable for nasal delivery. Powders containing WIIV and either lactose or trehalose were produced by lyophilization. A micro-ball mill was used to reduce the lyophilized cake to sizes suitable for nasal delivery. Chitosan flakes were reduced in size using a cryo-milling technique. Milled powders were sieved between 45 and 125 microm aggregate sizes and characterized for particle size and distribution, morphology, and flow properties. Powders were blended in the micro-ball mill without the ball. Lyophilization followed by milling produced irregularly shaped, polydisperse particles with a median primary particle diameter of approximately 21 microm and a yield of approximately 37% of particles in the 45 to 125 microm particle size range. Flow properties of lactose and trehalose powders after lyophilization followed by milling and sieving were similar. Cryo-milling produced a small yield of particles in the desired size range (<10%). Lyophilization followed by milling and sieving produced particles suitable for nasal delivery with different physicochemical properties as a function of processing conditions and components of the formulation. Further optimization of particle size and morphology is required for these powders to be suitable for clinical evaluation.

  4. Veterinary vaccine nanotechnology: pulmonary and nasal delivery in livestock animals.

    PubMed

    Calderon-Nieva, Daniella; Goonewardene, Kalhari Bandara; Gomis, Susantha; Foldvari, Marianna

    2017-08-01

    Veterinary vaccine development has several similarities with human vaccine development to improve the overall health and well-being of species. However, veterinary goals lean more toward feasible large-scale administration methods and low cost to high benefit immunization. Since the respiratory mucosa is easily accessible and most infectious agents begin their infection cycle at the mucosa, immunization through the respiratory route has been a highly attractive vaccine delivery strategy against infectious diseases. Additionally, vaccines administered via the respiratory mucosa could lower costs by removing the need of trained medical personnel, and lowering doses yet achieving similar or increased immune stimulation. The respiratory route often brings challenges in antigen delivery efficiency with enough potency to induce immunity. Nanoparticle (NP) technology has been shown to enhance immune activation by producing higher antibody titers and protection. Although specific mechanisms between NPs and biological membranes are still under investigation, physical parameters such as particle size and shape, as well as biological tissue distribution including mucociliary clearance influence the protection and delivery of antigens to the site of action and uptake by target cells. For respiratory delivery, various biomaterials such as mucoadhesive polymers, lipids, and polysaccharides have shown enhanced antibody production or protection in comparison to antigen alone. This review presents promising NPs administered via the nasal or pulmonary routes for veterinary applications specifically focusing on livestock animals including poultry.

  5. Novel freeze-dried DDA and TPGS liposomes are suitable for nasal delivery of vaccine.

    PubMed

    Yusuf, Helmy; Ali, Ahlam A; Orr, Natalie; Tunney, Michael M; McCarthy, Helen O; Kett, Vicky L

    2017-11-25

    There is a pressing need for effective needle-free vaccines that are stable enough for use in the developing world and stockpiling. The inclusion of the cationic lipid DDA and the PEG-containing moiety TPGS into liposomes has the potential to improve mucosal delivery. The aim of this study was to develop stable lyophilized cationic liposomes based on these materials suitable for nasal antigen delivery. Liposomes containing DDA and TPGS were developed. Size and zeta potential measurements, ex vivo, CLSM cell penetration study and cell viability investigations were made. Preliminary immunisation and stability studies using ovalbumin were performed. The liposomes exhibited suitable size and charge for permeation across nasal mucosa. DDA and TPGS increased tissue permeation in ex vivo studies and cell uptake with good cell viability. The liposomes improved immune response both locally and vaginally when compared to i.m administration or control liposomes delivered nasally. Additionally, the lyophilized products demonstrated good stability in terms of Tg, size and antigen retention. This study has shown that the novel liposomes have potential for development as a mucosal vaccine delivery system. Furthermore, the stability of the lyophilized liposomes offers potential additional benefits in terms of thermal stability over liquid formats. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Development of chitosan-pullulan composite nanoparticles for nasal delivery of vaccines: in vivo studies.

    PubMed

    Cevher, Erdal; Salomon, Stefan K; Somavarapu, Satyanarayana; Brocchini, Steve; Alpar, H Oya

    2015-01-01

    Here, we aimed at developing chitosan/pullulan composite nanoparticles and testing their potential as novel systems for the nasal delivery of diphtheria toxoid (DT). All the chitosan derivatives [N-trimethyl (TMC), chloride and glutamate] and carboxymethyl pullulan (CMP) were synthesised and antigen-loaded composites were prepared by polyion complexation of chitosan and pullulan derivatives (particle size: 239-405 nm; surface charge: +18 and +27 mV). Their immunological effects after intranasal administration to mice were compared to intramuscular route. Composite nanoparticles induced higher levels of IgG responses than particles formed with chitosan derivative and antigen. Nasally administered TMC-pullulan composites showed higher DT serum IgG titre when compared with the other composites. Co-encapsulation of CpG ODN within TMC-CMP-DT nanoparticles resulted in a balanced Th1/Th2 response. TMC/pullulan composite nanoparticles also induced highest cytokine levels compared to those of chitosan salts. These findings demonstrated that TMC-CMP-DT composite nanoparticles are promising delivery system for nasal vaccination.

  7. Nasal-nanotechnology: revolution for efficient therapeutics delivery.

    PubMed

    Kumar, Amrish; Pandey, Aditya Nath; Jain, Sunil Kumar

    2016-01-01

    In recent years, nanotechnology-based delivery systems have gained interest to overcome the problems of restricted absorption of therapeutic agents from the nasal cavity, depending upon the physicochemical properties of the drug and physiological properties of the human nose. The well-tolerated and non-invasive nasal drug delivery when combined with the nanotechnology-based novel formulations and carriers, opens the way for the effective systemic and brain targeting delivery of various therapeutic agents. To accomplish competent drug delivery, it is imperative to recognize the interactions among the nanomaterials and the nasal biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signaling involved in patho-biology of the disease under consideration. Quite a few systems have been successfully formulated using nanomaterials for intranasal (IN) delivery. Carbon nanotubes (CNTs), chitosan, polylactic-co-glycolic acid (PLGA) and PLGA-based nanosystems have also been studied in vitro and in vivo for the delivery of several therapeutic agents which shown promising concentrations in the brain after nasal administration. The use of nanomaterials including peptide-based nanotubes and nanogels (NGs) for vaccine delivery via nasal route is a new approach to control the disease progression. In this review, the recent developments in nanotechnology utilized for nasal drug delivery have been discussed.

  8. Mannan-decorated thiolated Eudragit microspheres for targeting antigen presenting cells via nasal vaccination.

    PubMed

    Li, Hui-Shan; Singh, Bijay; Park, Tae-Eun; Hong, Zhong-Shan; Kang, Sang-Kee; Cho, Chong-Su; Choi, Yun-Jaie

    2015-12-01

    Mucosal vaccination of protein as an antigen requires appropriate delivery or adjuvant systems to deliver antigen to mucosal immune cells efficiently and generate valid immune responses. For successful nasal immunization, the obstacles imposed by the normal process of mucociliary clearance which limits residence time of applied antigens and low antigen delivery to antigen presenting cells (APCs) in nasal associated lymphoid tissue (NALT) need to be overcome for the efficient vaccination. Here, we prepared mucoadhesive and mannan-decorated thiolated Eudragit microspheres (Man-TEM) as a nasal vaccine carrier to overcome the limitations. Mucoadhesive thiolated Eudragit (TE) were decorated with mannan for targeting mannose receptors (MR) in antigen presenting cells (APCs) to obtain efficient immune responses. The potential adjuvant ability of Man-TEM for intranasal immunization was confirmed by in vitro and in vivo experiments. In mechanistic study using APCs in vitro, we obtained that Man-TEM enhanced the receptor-mediated endocytosis by stimulating the MR receptors of APCs. The nasal vaccination of OVA-loaded Man-TEM in mice showed higher levels of serum IgG and mucosal sIgA than the soluble OVA group due to the specific recognition of MR of APCs by the mannan in the Man-TEM. These results suggest that mucoadhesive and Man-TEM may be a promising candidate for nasal vaccine delivery system to elicit systemic and mucosal immunity. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as well as mucosal immunity in mice.

    PubMed

    Cao, Weiping; Kim, Jin Hyang; Reber, Adrian J; Hoelscher, Mary; Belser, Jessica A; Lu, Xiuhua; Katz, Jacqueline M; Gangappa, Shivaprakash; Plante, Martin; Burt, David S; Sambhara, Suryaprakash

    2017-06-05

    Sporadic, yet frequent human infections with avian H5N1 influenza A viruses continue to pose a potential pandemic threat. Poor immunogenicity of unadjuvanted H5N1 vaccines warrants developing novel adjuvants and formulations as well as alternate delivery systems to improve their immunogenicity and efficacy. Here, we show that Protollin, a nasal adjuvant composed of Neisseria meningitides outer membrane proteins non-covalently linked to Shigella flexneri 2a lipopolysaccharide, is a potent nasal adjuvant for an inactivated split virion H5N1 clade 1 A/Viet Nam1203/2004 (A/VN/1203/04) vaccine in a mouse model. Protollin-adjuvanted vaccines elicited enhanced serum protective hemagglutination inhibition titers, mucosal IgA responses, and H5N1-specific cell-mediated immunity that resulted in complete protection against a lethal challenge with a homologous virus as well as a heterologous clade 2 virus A/Indonesia/05/2005 (A/IN/05/05). Detailed analysis of adaptive immunity revealed that Protollin increased the frequency of lymphoid- as well as local tissue-resident antibody-secreting cells, local germinal center reaction of B cells, broad-spectrum of CD4 T cell response. Our findings suggest that nasal delivery of H5N1 vaccine with Protollin adjuvant can overcome the poor immunogenicity of H5N1 vaccines, induce both cellular and humoral immune responses, enhance protection against challenge with clade 1 and clade 2 H5N1 viruses and achieve significant antigen dose-sparing. Copyright © 2017. Published by Elsevier Ltd.

  10. Smart Polymers in Nasal Drug Delivery

    PubMed Central

    Chonkar, Ankita; Nayak, Usha; Udupa, N.

    2015-01-01

    Nasal drug delivery has now been recognized as a promising route for drug delivery due to its capability of transporting a drug to systemic circulation and central nervous system. Though nasal mucosa offers improved bioavailability and quick onset of action of the drug, main disadvantage associated with nasal drug delivery is mucocilliary clearance due to which drug particles get cleared from the nose before complete absorption through nasal mucosa. Therefore, mucoadhesive polymeric approach can be successfully used to enhance the retention of the drug on nasal mucosal surface. Here, some of the aspects of the stimuli responsive polymers have been discussed which possess liquid state at the room temperature and in response to nasal temperature, pH and ions present in mucous, can undergo in situ gelation in nasal cavity. In this review, several temperature responsive, pH responsive and ion responsive polymers used in nasal delivery, their gelling mechanisms have been discussed. Smart polymers not only able to enhance the retention of the drug in nasal cavity but also provide controlled release, ease of administration, enhanced permeation of the drug and protection of the drug from mucosal enzymes. Thus smart polymeric approach can be effectively used for nasal delivery of peptide drugs, central nervous system dugs and hormones. PMID:26664051

  11. Impaired airway mucociliary function reduces antigen-specific IgA immune response to immunization with a claudin-4-targeting nasal vaccine in mice.

    PubMed

    Suzuki, Hidehiko; Nagatake, Takahiro; Nasu, Ayaka; Lan, Huangwenxian; Ikegami, Koji; Setou, Mitsutoshi; Hamazaki, Yoko; Kiyono, Hiroshi; Yagi, Kiyohito; Kondoh, Masuo; Kunisawa, Jun

    2018-02-13

    Vaccine delivery is an essential element for the development of mucosal vaccine, but it remains to be investigated how physical barriers such as mucus and cilia affect vaccine delivery efficacy. Previously, we reported that C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) targeted claudin-4, which is expressed by the epithelium associated with nasopharynx-associated lymphoid tissue (NALT), and could be effective as a nasal vaccine delivery. Mice lacking tubulin tyrosine ligase-like family, member 1 (Ttll1-KO mice) showed mucus accumulation in nasal cavity due to the impaired motility of respiratory cilia. Ttll1-KO mice nasally immunized with C-CPE fused to pneumococcal surface protein A (PspA-C-CPE) showed reduced PspA-specific nasal IgA responses, impaired germinal center formation, and decreased germinal center B-cells and follicular helper T cells in the NALT. Although there was no change in the expression of claudin-4 in the NALT epithelium in Ttll1-KO mice, the epithelium was covered by a dense mucus that prevented the binding of PspA-C-CPE to NALT. However, administration of expectorant N-acetylcysteine removed the mucus and rescued the PspA-specific nasal IgA response. These results show that the accumulation of mucus caused by impaired respiratory cilia function is an interfering factor in the C-CPE-based claudin-4-targeting nasal vaccine.

  12. Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review

    PubMed Central

    Islam, Mohammad Ariful; Firdous, Jannatul; Choi, Yun-Jaie; Yun, Cheol-Heui; Cho, Chong-Su

    2012-01-01

    Chitosan, a natural biodegradable polymer, is of great interest in biomedical research due to its excellent properties including bioavailability, nontoxicity, high charge density, and mucoadhesivity, which creates immense potential for various pharmaceutical applications. It has gelling properties when it interacts with counterions such as sulfates or polyphosphates and when it crosslinks with glutaraldehyde. This characteristic facilitates its usefulness in the coating or entrapment of biochemicals, drugs, antigenic molecules as a vaccine candidate, and microorganisms. Therefore, chitosan together with the advance of nanotechnology can be effectively applied as a carrier system for vaccine delivery. In fact, chitosan microspheres have been studied as a promising carrier system for mucosal vaccination, especially via the oral and nasal route to induce enhanced immune responses. Moreover, the thiolated form of chitosan is of considerable interest due to its improved mucoadhesivity, permeability, stability, and controlled/extended release profile. This review describes the various methods used to design and synthesize chitosan microspheres and recent updates on their potential applications for oral and nasal delivery of vaccines. The potential use of thiolated chitosan microspheres as next-generation mucosal vaccine carriers is also discussed. PMID:23271909

  13. Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives

    PubMed Central

    Xu, Yingying; Yuen, Pak-Wai; Lam, Jenny Ka-Wing

    2014-01-01

    Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT). Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV) etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents. PMID:25014738

  14. Breath Powered Nasal Delivery: A New Route to Rapid Headache Relief

    PubMed Central

    Djupesland, Per G; Messina, John C; Mahmoud, Ramy A

    2013-01-01

    The nose offers an attractive noninvasive alternative for drug delivery. Nasal anatomy, with a large mucosal surface area and high vascularity, allows for rapid systemic absorption and other potential benefits. However, the complex nasal geometry, including the narrow anterior valve, poses a serious challenge to efficient drug delivery. This barrier, plus the inherent limitations of traditional nasal delivery mechanisms, has precluded achievement of the full potential of nasal delivery. Breath Powered bi-directional delivery, a simple but novel nasal delivery mechanism, overcomes these barriers. This innovative mechanism has now been applied to the delivery of sumatriptan. Multiple studies of drug deposition, including comparisons of traditional nasal sprays to Breath Powered delivery, demonstrate significantly improved deposition to superior and posterior intranasal target sites beyond the nasal valve. Pharmacokinetic studies in both healthy subjects and migraineurs suggest that improved deposition of sumatriptan translates into improved absorption and pharmacokinetics. Importantly, the absorption profile is shifted toward a more pronounced early peak, representing nasal absorption, with a reduced late peak, representing predominantly gastrointestinal (GI) absorption. The flattening and “spreading out” of the GI peak appears more pronounced in migraine sufferers than healthy volunteers, likely reflecting impaired GI absorption described in migraineurs. In replicated clinical trials, Breath Powered delivery of low-dose sumatriptan was well accepted and well tolerated by patients, and onset of pain relief was faster than generally reported in previous trials with noninjectable triptans. Interestingly, Breath Powered delivery also allows for the potential of headache-targeted medications to be better delivered to the trigeminal nerve and the sphenopalatine ganglion, potentially improving treatment of various types of headache. In brief, Breath Powered bi

  15. Porous nanoparticles as delivery system of complex antigens for an effective vaccine against acute and chronic Toxoplasma gondii infection.

    PubMed

    Dimier-Poisson, Isabelle; Carpentier, Rodolphe; N'Guyen, Thi Thanh Loi; Dahmani, Fatima; Ducournau, Céline; Betbeder, Didier

    2015-05-01

    Development of sub-unit mucosal vaccines requires the use of specific delivery systems or immune-modulators such as adjuvants to improve antigen immunogenicity. Nasal route for vaccine delivery by nanoparticles has attracted much interest but mechanisms triggering effective mucosal and systemic immune response are still poorly understood. Here we study the loading of porous nanoparticles (DGNP) with a total extract of Toxoplasma gondii antigens (TE), the delivery of TE by DGNP into airway epithelial, macrophage and dendritic cells, and the subsequent cellular activation. In vitro, DGNP are able to load complex antigens in a stable and quantitative manner. The outstanding amount of antigen association by DGNP is used to deliver TE in airway mucosa cells to induce a cellular maturation with an increased secretion of pro-inflammatory cytokines. Evaluation of nasal vaccine efficiency is performed in vivo on acute and chronic toxoplasmosis mouse models. A specific Th1/Th17 response is observed in vivo after vaccination with DGNP/TE. This is associated with high protection against toxoplasmosis regarding survival and parasite burden, correlated with an increased delivery of antigens by DGNP in airway mucosa cells. This study provides evidence of the potential of DGNP for the development of new vaccines against a range of pathogens. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Anthrax vaccine powder formulations for nasal mucosal delivery.

    PubMed

    Jiang, Ge; Joshi, Sangeeta B; Peek, Laura J; Brandau, Duane T; Huang, Juan; Ferriter, Matthew S; Woodley, Wendy D; Ford, Brandi M; Mar, Kevin D; Mikszta, John A; Hwang, C Robin; Ulrich, Robert; Harvey, Noel G; Middaugh, C Russell; Sullivan, Vincent J

    2006-01-01

    Anthrax remains a serious threat worldwide as a bioterror agent. A second-generation anthrax vaccine currently under clinical evaluation consists of a recombinant Protective Antigen (rPA) of Bacillus anthracis. We have previously demonstrated that complete protection against inhalational anthrax can be achieved in a rabbit model, by intranasal delivery of a powder rPA formulation. Here we describe the preformulation and formulation development of such powder formulations. The physical stability of rPA was studied in solution as a function of pH and temperature using circular dichroism (CD), and UV-visible absorption and fluorescence spectroscopies. Extensive aggregation of rPA was observed at physiological temperatures. An empirical phase diagram, constructed using a combination of CD and fluorescence data, suggests that rPA is most thermally stable within the pH range of 6-8. To identify potential stabilizers, a library of GRAS excipients was screened using an aggregation sensitive turbidity assay, CD, and fluorescence. Based on these stability profiles, spray freeze-dried (SFD) formulations were prepared at pH 7-8 using trehalose as stabilizer and a CpG-containing oligonucleotide adjuvant. SFD formulations displayed substantial improvement in storage stability over liquid formulations. In combination with noninvasive intranasal delivery, such powder formulations may offer an attractive approach for mass biodefense immunization.

  17. Effects of nasal drug delivery device and its orientation on sprayed particle deposition in a realistic human nasal cavity.

    PubMed

    Tong, Xuwen; Dong, Jingliang; Shang, Yidan; Inthavong, Kiao; Tu, Jiyuan

    2016-10-01

    In this study, the effects of nasal drug delivery device and the spray nozzle orientation on sprayed droplets deposition in a realistic human nasal cavity were numerically studied. Prior to performing the numerical investigation, an in-house designed automated actuation system representing mean adults actuation force was developed to produce realistic spray plume. Then, the spray plume development was filmed by high speed photography system, and spray characteristics such as spray cone angle, break-up length, and average droplet velocity were obtained through off-line image analysis. Continuing studies utilizing those experimental data as boundary conditions were applied in the following numerical spray simulations using a commercially available nasal spray device, which was inserted into a realistic adult nasal passage with external facial features. Through varying the particle releasing direction, the deposition fractions of selected particle sizes on the main nasal passage for targeted drug delivery were compared. The results demonstrated that the middle spray direction showed superior spray efficiency compared with upper or lower directions, and the 10µm agents were the most suitable particle size as the majority of sprayed agents can be delivered to the targeted area, the main passage. This study elaborates a comprehensive approach to better understand nasal spray mechanism and evaluate its performance for existing nasal delivery practices. Results of this study can assist the pharmaceutical industry to improve the current design of nasal drug delivery device and ultimately benefit more patients through optimized medications delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Intranasal vaccination with an inactivated whole influenza virus vaccine induces strong antibody responses in serum and nasal mucus of healthy adults

    PubMed Central

    Ainai, Akira; Tamura, Shin-ichi; Suzuki, Tadaki; van Riet, Elly; Ito, Ryo; Odagiri, Takato; Tashiro, Masato; Kurata, Takeshi; Hasegawa, Hideki

    2013-01-01

    Haemagglutination inhibition (HI) and neutralization (NT) titers as well as haemagglutinin (HA) specific antibody responses were examined in 50 healthy adults aged between 22 and 69 y old after two intranasal administrations of an inactivated whole virus vaccine derived from A/Victoria/210/2009 virus (45 μg HA per dose) at 3 week intervals. Serum HI titers after two-doses of the nasal vaccine showed >2.5-fold rise in the ratio of geometric mean titer upon vaccination, >40% of subjects with a ≥4-fold increase in titer and >70% of subjects with a titer of ≥1:40, all parameters associated with an effective outcome of vaccination in the criteria defined by the European Medicines Agency. Serum neutralizing antibody responses correlated with HI antibody responses, although NT titers were about 2-fold higher than HI titers. These high levels of serum responses were accompanied by high levels of HI and neutralizing antibody responses in nasal mucus as measured in concentrated nasal wash samples that were about 10 times diluted compared with natural nasal mucus. Serum and nasal HI and neutralizing antibody responses consisted of HA-specific IgG and IgA antibody responses, with IgG and IgA antibodies being dominant in serum and nasal responses, respectively. PMID:23896606

  19. Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines

    NASA Astrophysics Data System (ADS)

    Nochi, Tomonori; Yuki, Yoshikazu; Takahashi, Haruko; Sawada, Shin-Ichi; Mejima, Mio; Kohda, Tomoko; Harada, Norihiro; Kong, Il Gyu; Sato, Ayuko; Kataoka, Nobuhiro; Tokuhara, Daisuke; Kurokawa, Shiho; Takahashi, Yuko; Tsukada, Hideo; Kozaki, Shunji; Akiyoshi, Kazunari; Kiyono, Hiroshi

    2010-07-01

    Nanotechnology is an innovative method of freely controlling nanometre-sized materials. Recent outbreaks of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce both systemic and mucosal antigen-specific immune responses. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel (`nanogel') consisting of a cationic type of cholesteryl-group-bearing pullulan (cCHP). A non-toxic subunit fragment of Clostridium botulinum type-A neurotoxin BoHc/A administered intranasally with cCHP nanogel (cCHP-BoHc/A) continuously adhered to the nasal epithelium and was effectively taken up by mucosal dendritic cells after its release from the cCHP nanogel. Vigorous botulinum-neurotoxin-A-neutralizing serum IgG and secretory IgA antibody responses were induced without co-administration of mucosal adjuvant. Importantly, intranasally administered cCHP-BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover, intranasally immunized tetanus toxoid with cCHP nanogel induced strong tetanus-toxoid-specific systemic and mucosal immune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination.

  20. Parents' perceptions of influenza and why they accept or decline the nasal vaccine for their child.

    PubMed

    Moulsdale, Phoebe; Grant, Aimee; Fletcher, Margaret; Finn, Adam

    2017-04-11

    Background Nasal influenza vaccine is offered each year to all children from age two to higher age groups. There is little UK research on whether parents support this vaccination programme. Aim The aim of this study was to explore parents' perceptions of influenza as an illness in children and why they decide to accept or decline nasal influenza vaccine for their child. Method A survey was first distributed to parents via a single primary school. Ten parents were then sampled in semi-structured interviews. From the survey, 91% (n=78) of the parents favoured routine vaccinations but only 47% (n=40) were supportive of nasal influenza vaccination. Findings From the interviews, reasons highlighted for accepting or declining the vaccine concerned the importance of trust, community responsibility, controllability and the perception of risk. Conclusion Parents who typically support vaccination may doubt the necessity of a influenza vaccination for their child. This may reduce uptake and undermine the programme.

  1. Live Attenuated B. pertussis as a Single-Dose Nasal Vaccine against Whooping Cough

    PubMed Central

    Mielcarek, Nathalie; Debrie, Anne-Sophie; Raze, Dominique; Bertout, Julie; Rouanet, Carine; Younes, Amena Ben; Creusy, Colette; Engle, Jacquelyn; Goldman, William E; Locht, Camille

    2006-01-01

    Pertussis is still among the principal causes of death worldwide, and its incidence is increasing even in countries with high vaccine coverage. Although all age groups are susceptible, it is most severe in infants too young to be protected by currently available vaccines. To induce strong protective immunity in neonates, we have developed BPZE1, a live attenuated Bordetella pertussis strain to be given as a single-dose nasal vaccine in early life. BPZE1 was developed by the genetic inactivation or removal of three major toxins. In mice, BPZE1 was highly attenuated, yet able to colonize the respiratory tract and to induce strong protective immunity after a single nasal administration. Protection against B. pertussis was comparable to that induced by two injections of acellular vaccine (aPV) in adult mice, but was significantly better than two administrations of aPV in infant mice. Moreover, BPZE1 protected against Bordetella parapertussis infection, whereas aPV did not. BPZE1 is thus an attractive vaccine candidate to protect against whooping cough by nasal, needle-free administration early in life, possibly at birth. PMID:16839199

  2. [Effect of absorption enhancers on nasal ginsenoside Rg1 delivery and its nasal ciliotoxicity].

    PubMed

    Chen, Xin-mei; Zhu, Jia-bi; Sun, Wei-dong; Zhang, Li-jian

    2006-02-01

    The enhancing activity and safety of several absorption enhancers were evaluated as potential nasal absorption enhancers to increase intranasal absorption of ginsenoside Rg1. Nasal circulatory perfusion test in vivo had been employed to investigate the effect of absorption enhancers for nasal mucosa absorption of ginsenoside Rgl in rats. The safety of the absorption enhancers were evaluated by testing cilia movement of the in situ toad palate model, the hemolysis of erythrocyte membrane of the rabbit, leaching of protein and LDH from the mice nasal mucosa and the effect on cilia structural and specific cellular changes of nasal mucosa. Absorption enhancers were necessary to facilitate ginsenoside Rg1 absorption by nasal mucosa. Among the absorption enhancers 1% sodium deoxycholate had great effect to facilite ginsenoside Rgl absorption by nasal mucosa; 1% dipotassium glycyrrhizinate and 1% azone had moderate effect to facilitate ginsenoside Rg1 absorption by nasal mucosa; 1% Tween-80, 2% beta-cyclodextrin, 0.5% borneol (dissolved in paraffin liquid), 0.5% chitosan, 5% hydroxypropyl-beta-cyclodextrin and 0.1% EDTA had low effect to facilitate ginsenoside Rgl absorption by nasal mucosa. 1% sodium deoxycholate, 1% azone and 1% dipotassium glycyrrhizinate had serious nasal toxicity; 1% Tween-80, 2% beta-cyclodextrin, 5% hydroxypropyl-beta-cyclodextrin had moderate nasal toxicity; 0.5% borneol (dissolved in paraffin liquid), 0.5% chitosan and 0.1% EDTA have little nasal toxicity. 0.5% borneol and 0.5% chitosan were the promising candidates having a good balance between enhancing activity and safety for nasal ginsenoside Rg1 delivery.

  3. Nasal Drug Delivery in Traditional Persian Medicine

    PubMed Central

    Zarshenas, Mohammad Mehdi; Zargaran, Arman; Müller, Johannes; Mohagheghzadeh, Abdolali

    2013-01-01

    Background Over one hundred different pharmaceutical dosage forms have been recorded in literatures of Traditional Persian Medicine among which nasal forms are considerable. Objectives This study designed to derive the most often applied nasal dosage forms together with those brief clinical administrations. Materials and Methods In the current study remaining pharmaceutical manuscripts of Persia during 9th to 18th century AD have been studied and different dosage forms related to nasal application of herbal medicines and their therapeutic effects were derived. Results By searching through pharmaceutical manuscripts of medieval Persia, different nasal dosage forms involving eleven types related to three main groups are found. These types could be derived from powder, solution or liquid and gaseous forms. Gaseous form were classified into fumigation (Bakhoor), vapor bath (Enkebab), inhalation (Lakhlakheh), aroma agents (Ghalieh) and olfaction or smell (Shomoom). Nasal solutions were as drops (Ghatoor), nasal snuffing drops (Saoot) and liquid snuff formulations (Noshoogh). Powders were as nasal insufflation or snorting agents (Nofookh) and errhine or sternutator medicine (Otoos). Nasal forms were not applied only for local purposes. Rather systemic disorders and specially CNS complications were said to be a target for these dosage forms. Discussion While this novel type of drug delivery is known as a suitable substitute for oral and parenteral administration, it was well accepted and extensively mentioned in Persian medical and pharmaceutical manuscripts and other traditional systems of medicine as well. Accordingly, medieval pharmaceutical standpoints on nasal dosage forms could still be an interesting subject of study. Therefore, the current work can briefly show the pharmaceutical knowledge on nasal formulations in medieval Persia and clarify a part of history of traditional Persian pharmacy. PMID:24624204

  4. Insulin delivery through nasal route using thiolated microspheres.

    PubMed

    Nema, Tarang; Jain, Ashish; Jain, Aviral; Shilpi, Satish; Gulbake, Arvind; Hurkat, Pooja; Jain, Sanjay K

    2013-01-01

    The aim of the present study was to investigate the potential of developed thiolated microspheres for insulin delivery through nasal route. In the present study, cysteine was immobilized on carbopol using EDAC. A total of 269.93 µmol free thiol groups per gram polymer were determined. The prepared nonthiolated and thiolated microspheres were studied for particle shape, size, drug content, swellability, mucoadhesion and in vitro insulin release. The thiolated microspheres exhibited higher mucoadhesion due to formation of covalent bonds via disulfide bridges with the mucus gel layer. Drug permeation through goat nasal mucosa of nonthiolated and thiolated microspheres were found as 52.62 ± 2.4% and 78.85 ± 3.1% in 6 h, respectively. Thiolated microspheres bearing insulin showed better reduction in blood glucose level (BGL) in comparison to nonthiolated microspheres as 31.23 ± 2.12% and 75.25 ± 0.93% blood glucose of initial BGL were observed at 6 h after nasal delivery of thiolated and nonthiolated microspheres in streptozotocin-induced diabetic rabbits.

  5. Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: implications for nasal physiology and drug delivery

    PubMed Central

    Kumar, Niyanta N.; Gautam, Mohan; Lochhead, Jeffrey J.; Wolak, Daniel J.; Ithapu, Vamsi; Singh, Vikas; Thorne, Robert G.

    2016-01-01

    Intranasal administration provides a non-invasive drug delivery route that has been proposed to target macromolecules either to the brain via direct extracellular cranial nerve-associated pathways or to the periphery via absorption into the systemic circulation. Delivering drugs to nasal regions that have lower vascular density and/or permeability may allow more drug to access the extracellular cranial nerve-associated pathways and therefore favor delivery to the brain. However, relative vascular permeabilities of the different nasal mucosal sites have not yet been reported. Here, we determined that the relative capillary permeability to hydrophilic macromolecule tracers is significantly greater in nasal respiratory regions than in olfactory regions. Mean capillary density in the nasal mucosa was also approximately 5-fold higher in nasal respiratory regions than in olfactory regions. Applying capillary pore theory and normalization to our permeability data yielded mean pore diameter estimates ranging from 13–17 nm for the nasal respiratory vasculature compared to <10 nm for the vasculature in olfactory regions. The results suggest lymphatic drainage for CNS immune responses may be favored in olfactory regions due to relatively lower clearance to the bloodstream. Lower blood clearance may also provide a reason to target the olfactory area for drug delivery to the brain. PMID:27558973

  6. Recent developments in leishmaniasis vaccine delivery systems.

    PubMed

    Bhowmick, Sudipta; Ali, Nahid

    2008-07-01

    The observation that recovery from infection with Leishmania confers immunity to reinfection suggests that control of leishmaniasis by vaccination may be possible. New generation vaccines, particularly those based on recombinant proteins and DNA, are found to be less immunogenic. There is an urgent need for the development of new and improved vaccine adjuvants. Based on their principal mechanisms of action, adjuvants can be broadly separated into two classes: immunostimulatory adjuvants and vaccine delivery systems. Vaccine delivery systems can carry both antigen and adjuvant for effective delivery to the antigen-presenting cells (APCs). In this article, we review the adjuvants, the delivery systems and their combinations used in the search of an effective vaccine against leishmaniasis. Based on current knowledge, cationic liposomes appear to have better prospects as effective delivery systems for developing a vaccine for leishmaniasis.

  7. Microneedles: quick and easy delivery methods of vaccines

    PubMed Central

    2017-01-01

    Vaccination is the most efficient method for infectious disease prevention. Parenteral injections such as intramuscular, intradermal, and subcutaneous injections have several advantages in vaccine delivery, but there are many drawbacks. Thus, the development of a new vaccine delivery system has long been required. Recently, microneedles have been attracting attention as new vaccination tools. Microneedle is a highly effective transdermal vaccine delivery method due to its mechanism of action, painlessness, and ease of use. Here, we summarized the characteristics of microneedles and the possibilities as a new vaccine delivery route. PMID:28775980

  8. Intradermal delivery of vaccines: potential benefits and current challenges

    PubMed Central

    Hickling, JK; Jones, KR; Friede, M; Chen, D; Kristensen, D

    2011-01-01

    Abstract Delivery of vaccine antigens to the dermis and/or epidermis of human skin (i.e. intradermal delivery) might be more efficient than injection into the muscle or subcutaneous tissue, thereby reducing the volumes of antigen. This is known as dose-sparing and has been demonstrated in clinical trials with some, but not all, vaccines. Dose-sparing could be beneficial to immunization programmes by potentially reducing the costs of purchase, distribution and storage of vaccines; increasing vaccine availability and effectiveness. The data obtained with intradermal delivery of some vaccines are encouraging and warrant further study and development; however significant gaps in knowledge and operational challenges such as reformulation, optimizing vaccine presentation and development of novel devices to aid intradermal vaccine delivery need to be addressed. Modelling of the costs and potential savings resulting from intradermal delivery should be done to provide realistic expectations of the potential benefits and to support cases for investment. Implementation and uptake of intradermal vaccine delivery requires further research and development, which depends upon collaboration between multiple stakeholders in the field of vaccination. PMID:21379418

  9. Bovine adenovirus-3 as a vaccine delivery vehicle.

    PubMed

    Ayalew, Lisanework E; Kumar, Pankaj; Gaba, Amit; Makadiya, Niraj; Tikoo, Suresh K

    2015-01-15

    The use of vaccines is an effective and relatively inexpensive means of controlling infectious diseases, which cause heavy economic losses to the livestock industry through animal loss, decreased productivity, treatment expenses and decreased carcass quality. However, some vaccines produced by conventional means are imperfect in many respects including virulence, safety and efficacy. Moreover, there are no vaccines for some animal diseases. Although genetic engineering has provided new ways of producing effective vaccines, the cost of production for veterinary use is a critical criterion for selecting the method of production and delivery of vaccines. The cost effective production and intrinsic ability to enter cells has made adenovirus vectors a highly efficient tool for delivery of vaccine antigens. Moreover, adenoviruses induce both humoral and cellular immune responses to expressed vaccine antigens. Since nonhuman adenoviruses are species specific, the development of animal specific adenoviruses as vaccine delivery vectors is being evaluated. This review summarizes the work related to the development of bovine adenovirus-3 as a vaccine delivery vehicle in animals, particularly cattle. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Development of a Soluplus budesonide freeze-dried powder for nasal drug delivery.

    PubMed

    Pozzoli, Michele; Traini, Daniela; Young, Paul M; Sukkar, Maria B; Sonvico, Fabio

    2017-09-01

    The aim of this work was to develop an amorphous solid dispersions/solutions (ASD) of a poorly soluble drug, budesonide (BUD) with a novel polymer Soluplus ® (BASF, Germany) using a freeze-drying technique, in order to improve dissolution and absorption through the nasal route. The small volume of fluid present in the nasal cavity limits the absorption of a poorly soluble drug. Budesonide is a corticosteroid, practically insoluble and normally administered as a suspension-based nasal spray. The formulation was prepared through freeze-drying of polymer-drug solution. The formulation was assessed for its physicochemical (specific surface area, calorimetric analysis and X-ray powder diffraction), release properties and aerodynamic properties as well as transport in vitro using RPMI 2650 nasal cells, in order to elucidate the efficacy of the Soluplus-BUD formulation. The freeze-dried Soluplus-BUD formulation (LYO) showed a porous structure with a specific surface area of 1.4334 ± 0.0178 m 2 /g. The calorimetric analysis confirmed an interaction between BUD and Soluplus and X-ray powder diffraction the amorphous status of the drug. The freeze-dried formulation (LYO) showed faster release compared to both water-based suspension and dry powder commercial products. Furthermore, a LYO formulation, bulked with calcium carbonate (LYO-Ca), showed suitable aerodynamic characteristics for nasal drug delivery. The permeation across RPMI 2650 nasal cell model was higher compared to a commercial water-based BUD suspension. Soluplus has been shown to be a promising polymer for the formulation of BUD amorphous solid suspension/solution. This opens up opportunities to develop new formulations of poorly soluble drug for nasal delivery.

  11. Advances in fish vaccine delivery.

    PubMed

    Plant, Karen P; Lapatra, Scott E

    2011-12-01

    Disease prevention is essential to the continued development of aquaculture around the world. Vaccination is the most effective method of combating disease and currently there are a number of vaccines commercially available for use in fish. The majority of aquatic vaccines are delivered by injection, which is by far the most effective method when compared to oral or immersion deliveries. However it is labor intensive, costly and not feasible for large numbers of fish under 20 g. Attempts to develop novel oral and immersion delivery methods have resulted in varying degrees of success but may have great potential for the future. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Nasal-to-CNS drug delivery: where are we now and where are we heading? An industrial perspective.

    PubMed

    Landis, Margaret S; Boyden, Tracey; Pegg, Simon

    2012-02-01

    Delivery of drug therapeutics across the blood-brain barrier is a challenging task for pharmaceutical scientists. Nasal-to-CNS drug delivery has shown promising results in preclinical efficacy models and investigatory human clinical trials. The further development of this technology with respect to the establishment of valid, predictable preclinical species models, translatable pharmacokinetic-pharmacodynamic relationships and definition of toxicology impact will help attract additional pharmaceutical investment in this drug-delivery approach. Further discoveries in nasal nanotechnology, targeted delivery devices and diagnostic olfactory imaging will serve to fuel the advancements in this area of drug delivery.

  13. Minipigs as an Animal Model for Dermal Vaccine Delivery

    PubMed Central

    Ploemen, Ivo HJ; Hirschberg, Hoang JHB; Kraan, Heleen; Zeltner, Adrian; van Kuijk, Sandra; Lankveld, Danielle PK; Royals, Michael; Kersten, Gideon FA; Amorij, Jean-Pierre

    2014-01-01

    Appropriate animal models for intradermal vaccine delivery are scarce. Given the high similarity of their skin anatomy to that of humans, minipigs may be a suitable model for dermal vaccine delivery. Here we describe the immunization of Göttingen minipigs by using intradermal and intramuscular delivery of hepatitis B surface antigen (HBsAg). Intradermal vaccine delivery by needle and syringe and by needle-free jet injection induced humoral antiHBsAg responses. Priming immunization by using the disposable syringe jet injector (DSJI) resulted in a higher antibody titer than did conventional intradermal immunization and a titer comparable to that after intramuscular vaccination with HBsAg and Al(OH)3 adjuvant. This study highlights the utility of the minipig model in vaccine studies assessing the efficacy of conventional and novel methods of dermal delivery. Moreover, we include suggestions regarding working with minipigs during dermal vaccine delivery studies, thereby fostering future work in this area of vaccinology. PMID:24512961

  14. Improving the safety of vaccine delivery.

    PubMed

    Evans, Huw P; Cooper, Alison; Williams, Huw; Carson-Stevens, Andrew

    2016-05-03

    Vaccines save millions of lives per annum as an integral part of community primary care provision worldwide. Adverse events due to the vaccine delivery process outnumber those arising from the pharmacological properties of the vaccines themselves. Whilst one in three patients receiving a vaccine will encounter some form of error, little is known about their underlying causes and how to mitigate them in practice. Patient safety incident reporting systems and adverse drug event surveillance offer a rich opportunity for understanding the underlying causes of those errors. Reducing harm relies on the identification and implementation of changes to improve vaccine safety at multiple levels: from patient interventions through to organizational actions at local, national and international levels. Here we highlight the potential for maximizing learning from patient safety incident reports to improve the quality and safety of vaccine delivery.

  15. Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs.

    PubMed

    Dhakal, Santosh; Renu, Sankar; Ghimire, Shristi; Shaan Lakshmanappa, Yashavanth; Hogshead, Bradley T; Feliciano-Ruiz, Ninoshkaly; Lu, Fangjia; HogenEsch, Harm; Krakowka, Steven; Lee, Chang Won; Renukaradhya, Gourapura J

    2018-01-01

    Annually, swine influenza A virus (SwIAV) causes severe economic loss to swine industry. Currently used inactivated SwIAV vaccines administered by intramuscular injection provide homologous protection, but limited heterologous protection against constantly evolving field viruses, attributable to the induction of inadequate levels of mucosal IgA and cellular immune responses in the respiratory tract. A novel vaccine delivery platform using mucoadhesive chitosan nanoparticles (CNPs) administered through intranasal (IN) route has the potential to elicit strong mucosal and systemic immune responses in pigs. In this study, we evaluated the immune responses and cross-protective efficacy of IN chitosan encapsulated inactivated SwIAV vaccine in pigs. Killed SwIAV H1N2 (δ-lineage) antigens (KAg) were encapsulated in chitosan polymer-based nanoparticles (CNPs-KAg). The candidate vaccine was administered twice IN as mist to nursery pigs. Vaccinates and controls were then challenged with a zoonotic and virulent heterologous SwIAV H1N1 (γ-lineage). Pigs vaccinated with CNPs-KAg exhibited an enhanced IgG serum antibody and mucosal secretory IgA antibody responses in nasal swabs, bronchoalveolar lavage (BAL) fluids, and lung lysates that were reactive against homologous (H1N2), heterologous (H1N1), and heterosubtypic (H3N2) influenza A virus strains. Prior to challenge, an increased frequency of cytotoxic T lymphocytes, antigen-specific lymphocyte proliferation, and recall IFN-γ secretion by restimulated peripheral blood mononuclear cells in CNPs-KAg compared to control KAg vaccinates were observed. In CNPs-KAg vaccinated pigs challenged with heterologous virus reduced severity of macroscopic and microscopic influenza-associated pulmonary lesions were observed. Importantly, the infectious SwIAV titers in nasal swabs [days post-challenge (DPC) 4] and BAL fluid (DPC 6) were significantly ( p  < 0.05) reduced in CNPs-KAg vaccinates but not in KAg vaccinates when compared to

  16. Development and gamma-scintigraphy study of Hibiscus rosasinensis polysaccharide-based microspheres for nasal drug delivery.

    PubMed

    Sharma, Nitin; Tyagi, Shanu; Gupta, Satish Kumar; Kulkarni, Giriraj Thirupathirao; Bhatnagar, Aseem; Kumar, Neeraj

    2016-11-01

    This work describes the application of natural plant polysaccharide as pharmaceutical mucoadhesive excipients in delivery systems to reduce the clearance rate through nasal cavity. Novel natural polysaccharide (Hibiscus rosasinensis)-based mucoadhesive microspheres were prepared by using emulsion crosslinking method for the delivery of rizatriptan benzoate (RB) through nasal route. Mucoadhesive microspheres were characterized for different parameters and nasal clearance of technetium-99m ((99m)Tc)-radiolabeled microspheres was determined by using gamma-scintigraphy. Their Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) studies showed that the drug was stable during preparation of microspheres. Aerodynamic diameter of microspheres was in the range 13.23 ± 1.83-33.57 ± 3.69 µm. Change in drug and polysaccharide ratio influenced the mucoadhesion, encapsulation efficiency and in-vitro release property. Scintigraphs taken at regular interval indicate that control solution was cleared rapidly from nasal cavity, whereas microspheres showed slower clearance (p < 0.005) with half-life of 160 min. Natural polysaccharide-based microspheres achieved extended residence by minimizing effect of mucociliary clearance with opportunity of sustained delivery for longer duration.

  17. CANINE DISTEMPER VIRUS ANTIBODY TITERS IN DOMESTIC CATS AFTER DELIVERY OF A LIVE ATTENUATED VIRUS VACCINE.

    PubMed

    Ramsay, Edward; Sadler, Ryan; Rush, Robert; Seimon, Tracie; Tomaszewicz, Ania; Fleetwood, Ellen A; McAloose, Denise; Wilkes, Rebecca P

    2016-06-01

    Three methods for delivering a live attenuated canine distemper virus (CDV) vaccine to domestic cats ( Felis catus ) were investigated, as models for developing vaccination protocols for tigers (Panthera tigris). Twenty domestic cats were randomly divided into four treatment groups: saline injection (negative controls); and oral, intranasal, and subcutaneous vaccinates. Cats were injected with saline or a CDV vaccine (Nobivac DP, Merck) at wk 0 and 4. Blood and nasal swabs were collected at wk 0 (prior to the initial vaccination) and weekly thereafter for 9 wk. Urine samples were collected on wk 1 to 9 after initial vaccination. Forty-nine weeks following the initial vaccination series, three cats from the subcutaneous group and three cats from the intranasal group were revaccinated. Blood was collected immediately prior, and 7 and 21 days subsequent to revaccination. Nasal swabs and urine samples were collected from each cat prior to wk 49 revaccination and daily for 7 days thereafter. Nasal swabs and urine were analyzed by quantitative PCR for vaccine virus presence. Sera were tested for CDV antibodies by virus neutralization. All cats were sero-negative for CDV antibodies at the beginning of the study, and saline-injected cats remained sero-negative throughout the study. A dramatic anamnestic response was seen following wk 4 subcutaneous vaccinations, with titers peaking at wk 6 (geometric mean = 2,435.5). Following wk 49 revaccination, subcutaneous vaccinates again mounted impressive titers (wk 52 geometric mean = 2,048). Revaccination of the intranasal group cats at wk 49 produced a small increase in titers (wk 52 geometric mean = 203). CDV viral RNA was detected in six nasal swabs but no urine samples, demonstrating low viral shedding postvaccination. The strong antibody response to subcutaneous vaccination and the lack of adverse effects suggest this vaccine is safe and potentially protective against CDV infection in domestic cats.

  18. Microneedle and mucosal delivery of influenza vaccines

    PubMed Central

    Kang, Sang-Moo; Song, Jae-Min; Kim, Yeu-Chun

    2017-01-01

    In recent years with the threat of pandemic influenza and other public health needs, alternative vaccination methods other than intramuscular immunization have received great attention. The skin and mucosal surfaces are attractive sites probably because of both non-invasive access to the vaccine delivery and unique immunological responses. Intradermal vaccines using a microinjection system (BD Soluvia) and intranasal vaccines (FluMist) are licensed. As a new vaccination method, solid microneedles have been developed using a simple device that may be suitable for self-administration. Because coated micorneedle influenza vaccines are administered in the solid state, developing formulations maintaining the stability of influenza vaccines is an important issue to be considered. Marketable microneedle devices and clinical trials remain to be developed. Other alternative mucosal routes such as oral and intranasal delivery systems are also attractive for inducing cross protective mucosal immunity but effective non-live mucosal vaccines remain to be developed. PMID:22697052

  19. Developments in the formulation and delivery of spray dried vaccines.

    PubMed

    Kanojia, Gaurav; Have, Rimko Ten; Soema, Peter C; Frijlink, Henderik; Amorij, Jean-Pierre; Kersten, Gideon

    2017-10-03

    Spray drying is a promising method for the stabilization of vaccines, which are usually formulated as liquids. Usually, vaccine stability is improved by spray drying in the presence of a range of excipients. Unlike freeze drying, there is no freezing step involved, thus the damage related to this step is avoided. The edge of spray drying resides in its ability for particles to be engineered to desired requirements, which can be used in various vaccine delivery methods and routes. Although several spray dried vaccines have shown encouraging preclinical results, the number of vaccines that have been tested in clinical trials is limited, indicating a relatively new area of vaccine stabilization and delivery. This article reviews the current status of spray dried vaccine formulations and delivery methods. In particular it discusses the impact of process stresses on vaccine integrity, the application of excipients in spray drying of vaccines, process and formulation optimization strategies based on Design of Experiment approaches as well as opportunities for future application of spray dried vaccine powders for vaccine delivery.

  20. Developments in the formulation and delivery of spray dried vaccines

    PubMed Central

    Kanojia, Gaurav; Have, Rimko ten; Soema, Peter C.; Frijlink, Henderik; Amorij, Jean-Pierre; Kersten, Gideon

    2017-01-01

    ABSTRACT Spray drying is a promising method for the stabilization of vaccines, which are usually formulated as liquids. Usually, vaccine stability is improved by spray drying in the presence of a range of excipients. Unlike freeze drying, there is no freezing step involved, thus the damage related to this step is avoided. The edge of spray drying resides in its ability for particles to be engineered to desired requirements, which can be used in various vaccine delivery methods and routes. Although several spray dried vaccines have shown encouraging preclinical results, the number of vaccines that have been tested in clinical trials is limited, indicating a relatively new area of vaccine stabilization and delivery. This article reviews the current status of spray dried vaccine formulations and delivery methods. In particular it discusses the impact of process stresses on vaccine integrity, the application of excipients in spray drying of vaccines, process and formulation optimization strategies based on Design of Experiment approaches as well as opportunities for future application of spray dried vaccine powders for vaccine delivery. PMID:28925794

  1. Nasal tip plasty: the delivery approach revisited.

    PubMed

    Xavier, Rui

    2013-02-01

    The delivery approach, though very appropriate for remodeling the tip of the nose, has been overlooked in recent years and has often been passed over for the open approach. One reason for this is the intercartilaginous incision used for the delivery approach, which may cause scarring at the nasal valve area, leading to postoperative functional obstruction of the nose. The delivery of the alar cartilages is another negative, as this maneuver will disrupt the collagen fibers that attach the upper lateral cartilages to the cephalic margin of the alar cartilages, leading to a weakening of the tip's support. We propose a modification to the traditional delivery approach by using a transcartilaginous instead of an intercartilaginous incision to prevent damage to the valve area. We also suggest taking advantage of the interference to the tip's support caused by the disruption of the collagen fibers of the scroll area. The purpose of this article is to describe this modification of the delivery approach and to emphasize the advantages that this controlled interference to the tip's support may have in selected cases. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  2. Enabling skin vaccination using new delivery technologies

    PubMed Central

    Kim, Yeu-Chun; Prausnitz, Mark R.

    2011-01-01

    The skin is known to be a highly immunogenic site for vaccination, but few vaccines in clinical use target skin largely because conventional intradermal injection is difficult and unreliable to perform. Now, a number of new or newly adapted delivery technologies have been shown to administer vaccine to the skin either by non-invasive or minimally invasive methods. Non-invasive methods include high-velocity powder and liquid jet injection, as well as diffusion-based patches in combination with skin abrasion, thermal ablation, ultrasound, electroporation, and chemical enhancers. Minimally invasive methods are generally based on small needles, including solid microneedle patches, hollow microneedle injections, and tattoo guns. The introduction of these advanced delivery technologies can make the skin a site for simple, reliable vaccination that increases vaccine immunogenicity and offers logistical advantages to improve the speed and coverage of vaccination. PMID:21799951

  3. Enabling skin vaccination using new delivery technologies

    PubMed Central

    Kim, Yeu-Chun; Prausnitz, Mark R.

    2011-01-01

    The skin is known to be a highly immunogenic site for vaccination, but few vaccines in clinical use target skin largely because conventional intradermal injection is difficult and unreliable to perform. Now, a number of new or newly adapted delivery technologies have been shown to administer vaccine to the skin either by non-invasive or minimally invasive methods. Non-invasive methods include high-velocity powder and liquid jet injection, as well as diffusion-based patches in combination with skin abrasion, thermal ablation, ultrasound, electroporation, and chemical enhancers. Minimally invasive methods are generally based on small needles, including solid microneedle patches, hollow microneedle injections and tattoo guns. The introduction of these advanced delivery technologies can make the skin a site for simple, reliable vaccination that increases vaccine immunogenicity and offers logistical advantages to improve the speed and coverage of vaccination. PMID:21472533

  4. Improved Pharmacokinetics of Sumatriptan With Breath Powered™ Nasal Delivery of Sumatriptan Powder

    PubMed Central

    Obaidi, Mohammad; Offman, Elliot; Messina, John; Carothers, Jennifer; Djupesland, Per G; Mahmoud, Ramy A

    2013-01-01

    Objectives.— The purpose of this study was to directly compare the pharmacokinetic (PK) profile of 22-mg sumatriptan powder delivered intranasally with a novel Breath Powered™ device (11 mg in each nostril) vs a 20-mg sumatriptan liquid nasal spray, a 100-mg oral tablet, and a 6-mg subcutaneous injection. Background.— A prior PK study found that low doses of sumatriptan powder delivered intranasally with a Breath Powered device were efficiently and rapidly absorbed. An early phase clinical trial with the same device and doses found excellent tolerability with high response rates and rapid onset of pain relief, approaching the benefits of injection despite significantly lower predicted drug levels. Methods.— An open-label, cross-over, comparative bioavailability study was conducted in 20 healthy subjects at a single center in the USA. Following randomization, fasted subjects received a single dose of each of the 4 treatments separated by a 7-day washout. Blood samples were taken pre-dose and serially over 14 hours post-dose for PK analysis. Results.— Quantitative measurement of residuals in used Breath Powered devices demonstrated that the devices delivered 8 ± 0.9 mg (mean ± standard deviation) of sumatriptan powder in each nostril (total dose 16 mg). Although the extent of systemic exposure over 14 hours was similar following Breath Powered delivery of 16-mg sumatriptan powder and 20-mg liquid nasal spray (area under the curve [AUC]0-∞ 64.9 ng*hour/mL vs 61.1 ng*hour/mL), sumatriptan powder, despite a 20% lower dose, produced 27% higher peak exposure (Cmax 20.8 ng/mL vs 16.4 ng/mL) and 61% higher exposure in the first 30 minutes compared with the nasal spray (AUC0-30 minutes 5.8 ng*hour/mL vs 3.6 ng*hour/mL). The magnitude of difference is larger on a per-milligram basis. The absorption profile following standard nasal spray demonstrated bimodal peaks, consistent with lower early followed by higher later absorptions. In

  5. Preliminary results from direct-to-facility vaccine deliveries in Kano, Nigeria.

    PubMed

    Aina, Muyi; Igbokwe, Uchenna; Jegede, Leke; Fagge, Rabiu; Thompson, Adam; Mahmoud, Nasir

    2017-04-19

    As part of its vaccine supply chain redesign efforts, Kano state now pushes vaccines directly from 6 state stores to primary health centers equipped with solar refrigerators. Our objective is to describe preliminary results from the first 20months of Kano's direct vaccine delivery operations. This is a retrospective review of Kano's direct vaccine delivery program. We analyzed trends in health facility vaccine stock levels, and examined the relationship between stock-out rates and each of cascade vaccine deliveries and timeliness of deliveries. Analysis of vaccination trends was based on administrative data from 27 sentinel health facilities. Costs for both the in-sourced and out-sourced approaches were estimated using a bottoms-up model-based approach. Overall stock adequacy increased from 54% in the first delivery cycle to 68% by cycle 33. Conversely, stock-out rates decreased from 41% to 10% over the same period. Similar trends were observed in the out-sourced and in-sourced programs. Stock-out rates rose incrementally with increasing number of cascade facilities, and delays in vaccine deliveries correlated strongly with stock-out rates. Recognizing that stock availability is one of many factors contributing to vaccinations, we nonetheless compared pre- and post- direct deliveries vaccinations in sentinel facilities, and found statistically significant upward trends for 4 out of 6 antigens. 1 antigen (measles) showed an upward trend that was not statistically significant. Hepatitis b vaccinations declined during the period. Overall, there appeared to be a one-year lag between commencement of direct deliveries and the increase in number of vaccinations. Weighted average cost per delivery is US$29.8 and cost per child immunized is US$0.7 per year. Direct vaccine delivery to health facilities in Kano, through a streamlined architecture, has resulted in decreased stock-outs and improved stock adequacy. Concurrent operation of insourced and outsourced programs has

  6. The influence of delivery vectors on HIV vaccine efficacy

    PubMed Central

    Ondondo, Beatrice O.

    2014-01-01

    Development of an effective HIV/AIDS vaccine remains a big challenge, largely due to the enormous HIV diversity which propels immune escape. Thus novel vaccine strategies are targeting multiple variants of conserved antibody and T cell epitopic regions which would incur a huge fitness cost to the virus in the event of mutational escape. Besides immunogen design, the delivery modality is critical for vaccine potency and efficacy, and should be carefully selected in order to not only maximize transgene expression, but to also enhance the immuno-stimulatory potential to activate innate and adaptive immune systems. To date, five HIV vaccine candidates have been evaluated for efficacy and protection from acquisition was only achieved in a small proportion of vaccinees in the RV144 study which used a canarypox vector for delivery. Conversely, in the STEP study (HVTN 502) where human adenovirus serotype 5 (Ad5) was used, strong immune responses were induced but vaccination was more associated with increased risk of HIV acquisition than protection in vaccinees with pre-existing Ad5 immunity. The possibility that pre-existing immunity to a highly promising delivery vector may alter the natural course of HIV to increase acquisition risk is quite worrisome and a huge setback for HIV vaccine development. Thus, HIV vaccine development efforts are now geared toward delivery platforms which attain superior immunogenicity while concurrently limiting potential catastrophic effects likely to arise from pre-existing immunity or vector-related immuno-modulation. However, it still remains unclear whether it is poor immunogenicity of HIV antigens or substandard immunological potency of the safer delivery vectors that has limited the success of HIV vaccines. This article discusses some of the promising delivery vectors to be harnessed for improved HIV vaccine efficacy. PMID:25202303

  7. Nasal delivery of analgesic ketorolac tromethamine thermo- and ion-sensitive in situ hydrogels.

    PubMed

    Li, Xin; Du, Lina; Chen, Xu; Ge, Pingju; Wang, Yu; Fu, Yangmu; Sun, Haiyan; Jiang, Qingwei; Jin, Yiguang

    2015-07-15

    Ketorolac tromethamine (KT) was potent to treat moderate to moderately severe pains. However, KT solutions for nasal delivery lost quickly from the nasal route. Thermo- and ion-sensitive in-situ hydrogels (ISGs) are appropriate for nasal drug delivery because the intranasal temperature maintains ∼37 °C and nasal fluids consist of plentiful cations. In this study, a novel nasal thermo- and ion-sensitive ISG of KT was prepared with thermo-sensitive poloxamer 407 (P407) and ion-sensitive deacetylated gellan gum (DGG). The optimal formulation of the KT ISG consisted of 3% (w/v) DGG and 18% (w/v) P407 and its viscosity was up to 7.63 Pas at 37 °C. Furthermore, penetration enhancers and bacterial inhibitors were added and their fractions in the ISG were optimized based on transmucosal efficiencies and toxicity on toad pili. Sulfobutyl ether-β-cyclodextrin of 2.5% (w/v) and chlorobutanol of 0.5% (w/v) were chosen as the penetration enhancer and the bacterial inhibitor, respectively. The Fick's diffusion and dissolution of KT could drive it continuous release from the dually sensitive ISG according to the in vitro investigation. Two methods, writhing frequencies induced by acetic acid and latency time of tails retracting from hot water, were used to evaluate the pharmacodynamics of the KT ISG on the mouse models. The writhing frequencies significantly decreased and the latency time of tail retracting was obviously prolonged (p<0.05) for the KT ISG compared to the control. The thermo- and ion-sensitive KT ISG had appropriate gelation temperature, sustained drug release, improved intranasal absorption, obvious pharmacodynamic effect, and negligible nasal ciliotoxicity. It is a promising intranasal analgesic formulation. Copyright © 2015. Published by Elsevier B.V.

  8. Polyethylenimine-based polyplex delivery of self-replicating RNA vaccines.

    PubMed

    Démoulins, Thomas; Milona, Panagiota; Englezou, Pavlos C; Ebensen, Thomas; Schulze, Kai; Suter, Rolf; Pichon, Chantal; Midoux, Patrick; Guzmán, Carlos A; Ruggli, Nicolas; McCullough, Kenneth C

    2016-04-01

    Self-amplifying replicon RNA (RepRNA) are large molecules (12-14 kb); their self-replication amplifies mRNA template numbers, affording several rounds of antigen production, effectively increasing vaccine antigen payloads. Their sensitivity to RNase-sensitivity and inefficient uptake by dendritic cells (DCs) - absolute requirements for vaccine design - were tackled by condensing RepRNA into synthetic, nanoparticulate, polyethylenimine (PEI)-polyplex delivery vehicles. Polyplex-delivery formulations for small RNA molecules cannot be transferred to RepRNA due to its greater size and complexity; the N:P charge ratio and impact of RepRNA folding would influence polyplex condensation, post-delivery decompaction and the cytosolic release essential for RepRNA translation. Polyplex-formulations proved successful for delivery of RepRNA encoding influenza virus hemagglutinin and nucleocapsid to DCs. Cytosolic translocation was facilitated, leading to RepRNA translation. This efficacy was confirmed in vivo, inducing both humoral and cellular immune responses. Accordingly, this paper describes the first PEI-polyplexes providing efficient delivery of the complex and large, self-amplifying RepRNA vaccines. The use of self-amplifying replicon RNA (RepRNA) to increase vaccine antigen payloads can potentially be useful in effective vaccine design. Nonetheless, its use is limited by the degradation during the uptake process. Here, the authors attempted to solve this problem by packaging RepRNA using polyethylenimine (PEI)-polyplex delivery vehicles. The efficacy was confirmed in vivo by the appropriate humoral and cellular immune responses. This novel delivery method may prove to be very useful for future vaccine design. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Novel adjuvants & delivery vehicles for vaccines development: a road ahead.

    PubMed

    Mohan, Teena; Verma, Priyanka; Rao, D Nageswara

    2013-11-01

    The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.

  10. Novel adjuvants & delivery vehicles for vaccines development: A road ahead

    PubMed Central

    Mohan, Teena; Verma, Priyanka; Rao, D. Nageswara

    2013-01-01

    The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines. PMID:24434331

  11. Microneedles for drug and vaccine delivery

    PubMed Central

    Kim, Yeu-Chun; Park, Jung-Hwan; Prausnitz, Mark R.

    2012-01-01

    Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990’s when microfabrication technology enabled their manufacture as (i) solid microneedles for skin pretreatment to increase skin permeability, (ii) microneedles coated with drug that dissolves off in the skin, (iii) polymer microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications. PMID:22575858

  12. Workshop report: Nucleic acid delivery devices for HIV vaccines: Workshop proceedings, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA, May 21, 2015.

    PubMed

    Weniger, Bruce G; Anglin, Ian E; Tong, Tina; Pensiero, Michael; Pullen, Jeffrey K

    2018-01-25

    On May 21st, 2015, the U.S. National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on delivery devices for nucleic acid (NA) as vaccines in order to review the landscape of past and future technologies for administering NA (e.g., DNA, RNA, etc.) as antigen into target tissues of animal models and humans. Its focus was on current and future applications for preventing and treating human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) disease, among other infectious-disease priorities. Meeting participants presented the results and experience of representative clinical trials of NA vaccines using a variety of alternative delivery devices, as well as a broader group of methods studied in animal models and at bench top, to improve upon the performance and/or avoid the drawbacks of conventional needle-syringe (N-S) delivery. The subjects described and discussed included (1) delivery targeted into oral, cutaneous/intradermal, nasal, upper and lower respiratory, and intramuscular tissues; (2) devices and techniques for jet injection, solid, hollow, and dissolving microneedles, patches for topical passive diffusion or iontophoresis, electroporation, thermal microporation, nasal sprayers, aerosol upper-respiratory and pulmonary inhalation, stratum-corneum ablation by ultrasound, chemicals, and mechanical abrasion, and kinetic/ballistic delivery; (3) antigens, adjuvants, and carriers such as DNA, messenger RNA, synthesized plasmids, chemokines, wet and dry aerosols, and pollen-grain and microparticle vectors; and (4) the clinical experience and humoral, cellular, and cytokine immune responses observed for many of these target tissues, technologies, constructs, and carriers. This report summarizes the presentations and discussions from the workshop (https://web.archive.org/web/20160228112310/https://www.blsmeetings.net/NucleicAcidDeliveryDevices/), which was webcast live in its entirety and archived online (http

  13. Vaccine vial stopper performance for fractional dose delivery of vaccines.

    PubMed

    Jarrahian, Courtney; Myers, Daniel; Creelman, Ben; Saxon, Eugene; Zehrung, Darin

    2017-07-03

    Shortages of vaccines such as inactivated poliovirus and yellow fever vaccines have been addressed by administering reduced-or fractional-doses, as recommended by the World Health Organization Strategic Advisory Group of Experts on Immunization, to expand population coverage in countries at risk. We evaluated 3 kinds of vaccine vial stoppers to assess their performance after increased piercing from repeated withdrawal of doses needed when using fractional doses (0.1 mL) from presentations intended for full-dose (0.5 mL) delivery. Self-sealing capacity and fragmentation of the stopper were assessed via modified versions of international standard protocols. All stoppers maintained self-sealing capacity after 100 punctures. The damage to stoppers measured as the fragmentation rate was within the target of ≤ 10% of punctures resulting in a fragment after as many as 50 punctures. We concluded that stopper failure is not likely to be a concern if existing vaccine vials containing up to 10 regular doses are used up to 50 times for fractional dose delivery.

  14. Vaccine vial stopper performance for fractional dose delivery of vaccines

    PubMed Central

    Jarrahian, Courtney; Myers, Daniel; Creelman, Ben; Saxon, Eugene; Zehrung, Darin

    2017-01-01

    ABSTRACT Shortages of vaccines such as inactivated poliovirus and yellow fever vaccines have been addressed by administering reduced—or fractional—doses, as recommended by the World Health Organization Strategic Advisory Group of Experts on Immunization, to expand population coverage in countries at risk. We evaluated 3 kinds of vaccine vial stoppers to assess their performance after increased piercing from repeated withdrawal of doses needed when using fractional doses (0.1 mL) from presentations intended for full-dose (0.5 mL) delivery. Self-sealing capacity and fragmentation of the stopper were assessed via modified versions of international standard protocols. All stoppers maintained self-sealing capacity after 100 punctures. The damage to stoppers measured as the fragmentation rate was within the target of ≤ 10% of punctures resulting in a fragment after as many as 50 punctures. We concluded that stopper failure is not likely to be a concern if existing vaccine vials containing up to 10 regular doses are used up to 50 times for fractional dose delivery. PMID:28463054

  15. Microneedle-mediated vaccine delivery: Harnessing cutaneous immunobiology to improve efficacy

    PubMed Central

    Al-Zahrani, S; Zaric, M; McCrudden, C; Scott, C; Kissenpfennig, A; Donnelly, Ryan F.

    2014-01-01

    Introduction We describe the use of microneedle arrays for delivery to targets within the skin itself. Breaching the skin’s stratum corneum barrier raises the possibility of administration of vaccines, gene vectors, antibodies and even nanoparticles, all of which have at least their initial effect on populations of skin cells. Areas Covered Intradermal vaccine delivery, in particular, holds enormous potential for improved therapeutic outcomes for patients, particularly those in the developing world. Various vaccine-delivery strategies have been employed and here we discuss each one in turn. We also describe the importance of cutaneous immunobiology on the effect produced by microneedle-mediated intradermal vaccination. Expert Opinion Microneedle-mediated vaccine holds enormous potential for patient benefit. In order for microneedle vaccine strategies to fulfil their potential, however, the proportion of an immune response that is due to local action of delivered vaccines on skin antigen presenting cells and what is due to a systemic effect from vaccine reaching the systemic circulation must be determined. Moreover, industry will need to invest significantly in new equipment and instrumentation in order to mass produce microneedle vaccines consistently. Finally, microneedles will need to demonstrate consistent dose delivery across patient groups and match this to reliable immune responses before they will replace tried- and-tested needle-and-syringe based-approaches. PMID:22475249

  16. Assessment of transcutaneous vaccine delivery by optical coherence tomography Assessment of transcutaneous vaccine delivery by OCT

    NASA Astrophysics Data System (ADS)

    Kamali, T.; Doronin, A.; Rattanapak, T.; Hook, S.; Meglinski, I.

    2012-08-01

    Immunization is one of the most efficient and cost-effective means for the prevention of diseases. The latest trend for inducing protective immunity is topical application of vaccines to intact skin rather than invasive administration via injection. Apart from being a non-invasive route of drug delivery, skin itself also offers advantages through the presence of cells of the immune system in both the dermis and epidermis. However, vaccine penetration through the outermost layers of skin is limited by the barrier provided by the Stratum corneum. In the current study utilizing conventional Optical Coherence Tomography (OCT) we investigate the transcutaneous delivery of a nano- particulate peptide vaccine into mouse skin in vivo. We demonstrate that a front of molecular diffusion within the skin can be clearly observed by using cross-correlations of successive 2D OCT images. Thus, OCT provides a unique tool for quantitative assessment of dynamics of diffusion of drugs, target compounds, analytes, cosmetics and various chemical agents in biological tissues in vivo.

  17. Leishmaniasis: focus on the design of nanoparticulate vaccine delivery systems.

    PubMed

    Doroud, Delaram; Rafati, Sima

    2012-01-01

    Although mass vaccination of the entire population of an endemic area would be the most cost-effective tool to diminish Leishmania burden, an effective vaccine is not yet commercially available. Practically, vaccines have failed to achieve the required level of protection, possibly owing to the lack of an appropriate adjuvant and/or delivery system. Therefore, there is still an imperative demand for an improved, safe and efficient delivery system to enhance the immunogenicity of available vaccine candidates. Nanoparticles are proficient in boosting the quality and magnitude of immune responses in a predictable fashion. Herein, we discuss how nanoparticulate vaccine delivery systems can be used to induce appropriate immune responses against leishmaniasis by controlling physicochemical properties of the vaccine. Stability, production reproducibility, low cost per dose and low risk-benefit ratios are desirable characteristics of an ideal vaccine formulation and solid lipid nanoparticles may serve as one of the most promising practical strategies to help to achieve such a leishmanial vaccine, at least in canine species in the developing world.

  18. Minor Consent and Delivery of Adolescent Vaccines

    PubMed Central

    Ford, Carol A.; Skiles, Martha P.; English, Abigail; Cai, Jianwen; Agans, Robert P.; Stokley, Shannon; Markowitz, Lauri; Koumans, Emilia H.

    2016-01-01

    Purpose To explore whether, and to what extent, minor consent influences adolescent vaccine delivery in the United States. Methods A telephone survey was completed by 263 professionals with responsibilities for adolescent health care and/or vaccination in 43 states. Measures included perceived frequency of unaccompanied minor visits and perceived likelihood of vaccine delivery to unaccompanied minors in hypothetical scenarios that varied by adolescent age, vaccine type, visit type, and clinical setting. Results Among the 76 respondents most familiar with private primary care clinics, 47.1% reported perceptions that 17-year-old patients often present without a parent/legal guardian. Among the 104 respondents most familiar with public primary care clinics, 56.7% reported that 17-year-old patients often present alone. In response to hypothetical scenarios, approximately 30% of respondents familiar with private clinics and 50% of respondents familiar with public clinics reported perceptions that unaccompanied 17-year-old adolescents would not receive influenza, Tdap, or human papillomavirus vaccines during routine check-ups because they could not provide consent. Perceived likelihood of unaccompanied minors receiving vaccines when seen for confidential services in primary care, sexually transmitted disease, and Title X/family planning clinics varied significantly by vaccine type and clinical setting. On average, respondents reported that they would support minors having the ability to self-consent for vaccines at age 14. Conclusions The inability of minors to consent for vaccines is likely one barrier to vaccination. Interventions to increase adolescent vaccination should consider strategies that increase the ability of unaccompanied minors, particularly older minors, to receive vaccines within the context of legal, ethical, and professional guidelines. PMID:24074605

  19. Recent trends in vaccine delivery systems: A review

    PubMed Central

    Saroja, CH; Lakshmi, PK; Bhaskaran, Shyamala

    2011-01-01

    Vaccines are the preparations given to patients to evoke immune responses leading to the production of antibodies (humoral) or cell-mediated responses that will combat infectious agents or noninfectious conditions such as malignancies. Alarming safety profile of live vaccines, weak immunogenicity of sub-unit vaccines and immunization, failure due to poor patient compliance to booster doses which should potentiate prime doses are few strong reasons, which necessitated the development of new generation of prophylactic and therapeutic vaccines to promote effective immunization. Attempts are being made to deliver vaccines through carriers as they control the spatial and temporal presentation of antigens to immune system thus leading to their sustained release and targeting. Hence, lower doses of weak immunogens can be effectively directed to stimulate immune responses and eliminate the need for the administration of prime and booster doses as a part of conventional vaccination regimen. This paper reviews carrier systems such as liposomes, microspheres, nanoparticles, dendrimers, micellar systems, ISCOMs, plant-derived viruses which are now being investigated and developed as vaccine delivery systems. This paper also describes various aspects of “needle-free technologies” used to administer the vaccine delivery systems through different routes into the human body. PMID:23071924

  20. Novel thermal-sensitive hydrogel enhances both humoral and cell-mediated immune responses by intranasal vaccine delivery.

    PubMed

    Wu, Youbin; Wu, Shipo; Hou, Lihua; Wei, Wei; Zhou, Meng; Su, Zhiguo; Wu, Jie; Chen, Wei; Ma, Guanghui

    2012-08-01

    A novel thermal sensitive hydrogel was formulated with N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) and α, β-glycerophosphate (α, β-GP). A serial of hydrogels containing different amount of GP and HTCC with diverse quarternize degree (QD, 41%, 59%, 79.5%, and 99%) were prepared and characterized by rheological method. The hydrogel was subsequently evaluated for intranasal vaccine delivery with adenovirus based Zaire Ebola virus glycoprotein antigen (Ad-GPZ). Results showed that moderate quarternized HTCC (60% and 79.5%) hydrogel/antigen formulations induced highest IgG, IgG1, and IgG2a antibody titers in serum, as well as mucosal IgA responses in lung wash, which may attributed to the prolonged antigen residence time due to the thermal-sensitivity of this hydrogel. Furthermore, CD8(+) splenocytes for IFN-γ positive cell assay and the release profile of Th1/Th2 type cytokines (IFN-γ, IL-2, IL-10, and IL-4) showed that hydrogel/Ad-GPZ generated an overwhelmingly enhanced Th1 biased cellular immune response. In addition, this hydrogel displayed low toxicity to nasal tissue and epithelial cells even by frequently intranasal dosing of hydrogel. All these results strongly supported this hydrogel as a safe and effective delivery system for nasal immunization. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  1. Intra-nasal infection of macaques with Yellow Fever (YF) vaccine strain 17D: a novel and economical approach for YF vaccination in man.

    PubMed

    Niedrig, M; Stolte, N; Fuchs, D; Hunsmann, G; Stahl-Hennig, C

    1999-03-05

    Investigating new and simple application routes for YF vaccine, four groups of 4-6 rhesus monkeys were vaccinated with live attenuated 17D YF-vaccine. In two groups the vaccine was administered either as spray into the oral cavity, or as an encapsulated form directly into the stomach. Only one out of eight animals developed a humoral immune response against 17D. In the third group receiving the vaccine intranasally by spray and in the fourth group serving as control all ten monkeys developed an immune response. From all except one of these seroconverted monkeys virus could be detected either by virus reisolation or RT-PCR. All these animals showed a serological immune response in immunofluorescence and neutralisation test. Parallel to viremia, an increase of neopterin as an unspecified immune activation marker could be demonstrated for these animals. Intra-nasal application of 17D-vaccine seems to be a good alternative to subcutaneous immunisation in mass vaccination campaigns.

  2. Mitochondrion: A Promising Target for Nanoparticle-Based Vaccine Delivery Systems

    PubMed Central

    Wen, Ru; Umeano, Afoma C.; Francis, Lily; Sharma, Nivita; Tundup, Smanla; Dhar, Shanta

    2016-01-01

    Vaccination is one of the most popular technologies in disease prevention and eradication. It is promising to improve immunization efficiency by using vectors and/or adjuvant delivery systems. Nanoparticle (NP)-based delivery systems have attracted increasing interest due to enhancement of antigen uptake via prevention of vaccine degradation in the biological environment and the intrinsic immune-stimulatory properties of the materials. Mitochondria play paramount roles in cell life and death and are promising targets for vaccine delivery systems to effectively induce immune responses. In this review, we focus on NPs-based delivery systems with surfaces that can be manipulated by using mitochondria targeting moieties for intervention in health and disease. PMID:27258316

  3. Financing and systems barriers to seasonal influenza vaccine delivery in community settings.

    PubMed

    Penfold, Robert B; Rusinak, Donna; Lieu, Tracy A; Shefer, Abigail; Messonnier, Mark; Lee, Grace M

    2011-12-06

    Recommendations for annual seasonal influenza vaccination have expanded to now include >300 million children and adults each year. Community settings have become increasingly important venues for influenza vaccination. We sought to identify barriers to and solutions for expanding influenza vaccination in community settings. Semi-structured telephone interviews were conducted from 01/09 to 06/10 with a range of stakeholders involved in influenza vaccination, including health plans, medical services firms, retail based clinics, pharmacies, schools, and state and local public health immunization programs. Participants (n=65) were asked about barriers and feasible solutions to influenza vaccine delivery to children and adults in community settings. Key themes were identified through iterative coding using a grounded theory approach. Stakeholders identified specific financial barriers to influenza vaccine delivery in 3 major areas: purchase and distribution, delivery, and reimbursement. Limited purchasing power, the uncertain nature of public demand, and unpredictable timing of influenza vaccine supply were important barriers to enhance delivery in community settings. Barriers to delivery included complexities in running off-site clinics, especially in school settings, the need to manage publicly vs. privately purchased vaccines separately, and state-to-state variability in requirements for credentialing, physician oversight, and reporting. Reimbursement barriers included a protracted credentialing process, the need to determine insurance eligibility at point-of-service, and lack of a billing infrastructure in off-site clinics. Opportunities to mitigate financial barriers to influenza vaccine delivery in community settings focused on coordination across providers and the role of public health as a "trusted broker" to overcome existing challenges. Financial and systems barriers hamper the optimal use of community settings to effectively deliver influenza vaccines. Public

  4. Intranasal delivery of Norwalk virus-like particles formulated in an in-situ gelling, dry powder vaccine

    PubMed Central

    Velasquez, Lissette S.; Shira, Samantha; Berta, Alice N.; Kilbourne, Jacquelyn; Medi, Babu M.; Tizard, Ian; Ni, Yawei; Arntzen, Charles J.; Herbst-Kralovetz, Melissa M.

    2011-01-01

    The development of a vaccine to prevent norovirus infections has been focused on immunization at a mucosal surface, but has been limited by the low immunogenicity of self-assembling Norwalk virus-like particles (NV VLPs) delivered enterically or at nasal surfaces. Nasal immunization, which offers the advantage of ease of immunization, faces obstacles imposed by the normal process of mucociliary clearance, which limits residence time of applied antigens. Herein, we describe the use of a dry powder formulation (GelVac) of an inert in-situ gelling polysaccharide (GelSite) extracted from Aloe vera for nasal delivery of NV VLP antigen. Powder formulations, with or without NV VLP antigen, were similar in structure in dry form or when rehydrated in simulated nasal fluids. Immunogenicity of the dry powder VLP formulation was compared to equivalent antigen/adjuvant liquid formulations in animals. For the GelVac powder, we observed superior NV-specific serum and mucosal (aerodigestive and reproductive tracts) antibody responses relative to liquid formulations. Incorporation of TLR7 agonist gardiquimod in dry powder formulations did not enhance antibody responses, although its inclusion in liquid formulations did enhance VLP immunogenicity irrespective of the presence or absence of GelSite. We interpret these data as showing that GelSite-based dry powder formulations 1.) stabilize the immunogenic structural properties of VLPs and 2.) induce systemic and mucosal antibody titers which are equal or greater than those achieved by VLPs plus adjuvant in a liquid formulation. We conclude that in-situ gelation of the GelVac dry powder formulation at nasal mucosal surfaces delays mucociliary clearance and thereby prolongs VLP antigen exposure to immune effector sites. PMID:21640778

  5. Particulate delivery systems for biodefense subunit vaccines.

    PubMed

    Bramwell, Vincent W; Eyles, Jim E; Oya Alpar, H

    2005-06-17

    Expanding identification of potentially protective subunit antigens and correlates of protection has provided a basis for the introduction of safer vaccines. Despite encouraging results in animal models, the significant potential of particulate delivery systems in vaccine design has not yet translated into effective vaccines available for use in humans. This review article will focus on the current status of the development of particulate vaccines, mainly liposomes and bio-degradable polymers, against potential agents for biowarfare: plague, anthrax, botulinum, and smallpox; and filoviruses: Marburg and Ebola.

  6. Mucosal Vaccination against Tuberculosis Using Inert Bioparticles

    PubMed Central

    Reljic, Rajko; Sibley, Laura; Huang, Jen-Min; Pepponi, Ilaria; Hoppe, Andreas; Hong, Huynh A.

    2013-01-01

    Needle-free, mucosal immunization is a highly desirable strategy for vaccination against many pathogens, especially those entering through the respiratory mucosa, such as Mycobacterium tuberculosis. Unfortunately, mucosal vaccination against tuberculosis (TB) is impeded by a lack of suitable adjuvants and/or delivery platforms that could induce a protective immune response in humans. Here, we report on a novel biotechnological approach for mucosal vaccination against TB that overcomes some of the current limitations. This is achieved by coating protective TB antigens onto the surface of inert bacterial spores, which are then delivered to the respiratory tract. Our data showed that mice immunized nasally with coated spores developed humoral and cellular immune responses and multifunctional T cells and, most importantly, presented significantly reduced bacterial loads in their lungs and spleens following pathogenic challenge. We conclude that this new vaccine delivery platform merits further development as a mucosal vaccine for TB and possibly also other respiratory pathogens. PMID:23959722

  7. Numerical Comparison of Nasal Aerosol Administration Systems for Efficient Nose-to-Brain Drug Delivery.

    PubMed

    Dong, Jingliang; Shang, Yidan; Inthavong, Kiao; Chan, Hak-Kim; Tu, Jiyuan

    2017-12-29

    Nose-to-brain drug administration along the olfactory and trigeminal nerve pathways offers an alternative route for the treatment of central nervous system (CNS) disorders. The characterization of particle deposition remains difficult to achieve in experiments. Alternative numerical approach is applied to identify suitable aerosol particle size with maximized inhaled doses. This study numerically compared the drug delivery efficiency in a realistic human nasal cavity between two aerosol drug administration systems targeting the olfactory region: the aerosol mask system and the breath-powered bi-directional system. Steady inhalation and exhalation flow rates were applied to both delivery systems. The discrete phase particle tracking method was employed to capture the aerosol drug transport and deposition behaviours in the nasal cavity. Both overall and regional deposition characteristics were analysed in detail. The results demonstrated the breath-powered drug delivery approach can produce superior olfactory deposition with peaking olfactory deposition fractions for diffusive 1 nm particles and inertial 10 μm. While for particles in the range of 10 nm to 2 μm, no significant olfactory deposition can be found, indicating the therapeutic agents should avoid this size range when targeting the olfactory deposition. The breath-powered bi-directional aerosol delivery approach shows better drug delivery performance globally and locally, and improved drug administration doses can be achieved in targeted olfactory region.

  8. Anthrax Vaccine Powder Formulations for Nasal Mucosal Delivery

    DTIC Science & Technology

    2005-08-04

    inhalational anthrax can be achieved in a rabbit model, by intranasal delivery of a powder rPA formulation. Here we describe the preformulation and...fluorescence. Based on these stability profiles, spray freeze-dried (SFD) formulations were prepared at pH 7–8 using trehalose as stabilizer and a CpG...gas- trointestinal, and pulmonary routes. The inhaled form is of particular concern considering its de- monstrated use as a bioweapon.1–4 Inhalational

  9. Application of optical coherence tomography for assessment of transcutaneous vaccine delivery

    NASA Astrophysics Data System (ADS)

    Kamali, T.; Rattanapak, T.; Hook, S.; Meglinski, I.

    2012-03-01

    Immunization is one of the most efficient and cost-effective means for the prevention of diseases, but most vaccines have to be administered invasively. A novel strategy of inducing an immune response is topical application of vaccines to intact skin. Apart from being a non-invasive route of drug delivery, skin delivery also offers an advantageous mode of immunization due to the ability of skin immune cells to present antigens to the immune system. Topical vaccine penetration through the outermost layers of skin is based on the percutaneous diffusion of lipid-based nano-particles. In the current study we investigate the applicability of Optical Coherence Tomography for monitoring transcutaneous delivery of a peptide vaccine into the skin in vivo.

  10. Comparison of interferon and bovine herpesvirus-1-specific IgA levels in nasal secretions of dairy cattle administered an intranasal modified live viral vaccine prior to calving or on the day of calving.

    PubMed

    Cortese, Victor S; Woolums, Amelia; Hurley, David J; Berghaus, Roy; Bernard, John K; Short, Thomas H

    2017-05-01

    Thirty-two Holstein cows were allocated to receive intranasal vaccination with modified live bovine herpesvirus-1 (BHV-1), bovine respiratory syncytial virus (BRSV) and parainfluenza type 3 virus (PI3V) vaccine either two weeks prior to their projected calving date, or within 24h after calving. Nasal secretions were collected twice at a 12-h interval on the day prior to vaccination (day 0) and at 2, 4, 7, 10 and 14days post vaccination to measure interferon (IFN) alpha, IFN-beta, IFN-gamma, and BHV-1-specific IgA by ELISA. Serum neutralizing antibody titers to BHV-1 and BRSV were measured on days 0, 7, and 14. There was a significant treatment effect (p<0.0004) and interaction (p<0.05) on nasal BHV-1 IgA levels, with higher IgA levels in cows vaccinated within 24h after calving. There was a significant treatment effect on nasal IFN-gamma concentration (p<0.05) and on nasal total IFN concentration (p<0.05), with higher IFN-gamma and total IFN concentrations seen in cows vaccinated within 24h after calving. There was no significant treatment or interaction effect on nasal IFN-alpha or IFN-beta concentrations, or on serum neutralizing titers to BRSV. In spite of prior viral vaccination during the previous lactation, cows vaccinated on the day of calving responded to an intranasal viral vaccination with increased concentrations of IFN-gamma and increased titers of IgA following vaccination which was significantly higher than cows vaccinated precalving. This study is the first to examine respiratory mucosal responses in immunologically mature dairy cattle vaccinated intranasally before and after calving. Copyright © 2017. Published by Elsevier B.V.

  11. Detection of lumpy skin disease virus in skin lesions, blood, nasal swabs and milk following preventive vaccination.

    PubMed

    Bedeković, T; Šimić, I; Krešić, N; Lojkić, I

    2018-04-01

    Lumpy skin disease caused by Capripoxvirus is at the moment the most important threat to European cattle industry. The only way for successful control of disease is fast and efficient diagnosis and vaccination. According to EU legislation, vaccination against LDS can be conducted only after confirmation of the disease. Croatia has a special position regarding LSD-in 2016, for the first-time vaccination of the entire cattle population was conducted without an index case. The presence of vaccine viral particles was detected in milk, skin nodules, blood and nasal swabs in seven from total of eight herds. The presence of virus genome was detected in five cows from 10 up to 21-day post-vaccination. The virus was successfully isolated on cell culture from 10 up to 21-day post-vaccination from three animals. The obtained results support the need for further efforts to develop safer vaccines against LSDV. © 2017 Blackwell Verlag GmbH.

  12. Nasal Vaccination Stimulates CD8+ T Cells for Potent Protection Against Mucosal Brucella melitensis Challenge

    PubMed Central

    Clapp, Beata; Yang, Xinghong; Thornburg, Theresa; Walters, Nancy; Pascual, David W.

    2016-01-01

    Brucellosis remains a significant zoonotic threat worldwide. Humans and animals acquire infection via their oropharynx and upper respiratory tract following oral or aerosol exposure. After mucosal infection, brucellosis develops into a systemic disease. Mucosal vaccination could offer a viable alternative to conventional injection practices to deter disease. Using a nasal vaccination approach, the ΔznuA B. melitensis was found to confer potent protection against pulmonary Brucella challenge, and reduce colonization of spleens and lungs by more than 2500-fold, with more than 50% of vaccinated mice showing no detectable brucellae. Furthermore, tenfold more brucellae-specific, IFN-γ-producing CD8+ T cells than CD4+ T cells were induced in the spleen and respiratory lymph nodes. Evaluation of pulmonary and splenic CD8+ T cells from mice vaccinated with ΔznuA B. melitensis revealed that these expressed an activated effector memory (CD44hiCD62LloCCR7lo) T cells producing elevated levels of IFN-γ, TNF-α, perforin, and granzyme B. To assess the relative importance of these increased numbers of CD8+ T cells, CD8−/− mice were challenged with virulent B. melitensis, and they showed markedly increased bacterial loads in organs in contrast to similarly challenged CD4−/− mice. Only ΔznuA B. melitensis- and Rev-1-vaccinated CD4−/− and wild-type mice, not CD8−/− mice, were completely protected against Brucella challenge. Determination of cytokines responsible for conferring protection showed the relative importance of IFN-γ, but not IL-17. Unlike wild-type mice, IL-17 was greatly induced in IFN-γ−/− mice, but IL-17 could not substitute for IFN-γ’s protection, although an increase in brucellae dissemination was observed upon in vivo IL-17 neutralization. These results show that nasal ΔznuA B. melitensis vaccination represents an attractive means to stimulate systemic and mucosal immune protection via CD8+ T cell engagement. PMID:26752510

  13. Intranasal Inactivated Influenza Vaccines: a Reasonable Approach to Improve the Efficacy of Influenza Vaccine?

    PubMed

    Tamura, Shin-Ichi; Ainai, Akira; Suzuki, Tadaki; Kurata, Takeshi; Hasegawa, Hideki

    2016-01-01

    Influenza is a contagious, acute respiratory disease caused by the influenza virus. The mucosal lining in the host respiratory tract is not only the site of virus infection, but also the site of defense; it is at this site that the host immune response targets the virus and protects against reinfection. One of the most effective methods to prevent influenza is to induce specific antibody (Ab) responses in the respiratory tract by vaccination. Two types of influenza vaccines, intranasal live attenuated influenza virus (LAIV) vaccines and parenteral (injectable) inactivated vaccines, are currently used worldwide. These vaccines are approved by the European Medicines Agency (EMA) and the US Food and Drug Administration. Live attenuated vaccines induce both secretory IgA (S-IgA) and serum IgG antibodies (Abs), whereas parenteral vaccines induce only serum IgG Abs. However, intranasal administration of inactivated vaccines together with an appropriate adjuvant induces both S-IgA and IgG Abs. Several preclinical studies on adjuvant-combined, nasal-inactivated vaccines revealed that nasal S-IgA Abs, a major immune component in the upper respiratory tract, reacted with homologous virus hemagglutinin (HA) and were highly cross-reactive with viral HA variants, resulting in protection and cross-protection against infection by both homologous and variant viruses, respectively. Serum-derived IgG Abs, which are present mainly in the lower respiratory tract, are less cross-reactive and cross-protective. In addition, our own clinical trials have shown that nasal-inactivated whole virus vaccines, including a built-in adjuvant (single-stranded RNA), induced serum hemagglutination inhibition (HI) Ab titers that fulfilled the EMA criteria for vaccine efficacy. The nasal-inactivated whole virus vaccines also induced high levels of nasal HI and neutralizing Ab titers, although we have not yet evaluated the nasal HI titers due to the lack of official criteria to establish efficacy based

  14. Coated microneedle arrays for transcutaneous delivery of live virus vaccines

    PubMed Central

    Vrdoljak, Anto; McGrath, Marie G.; Carey, John B.; Draper, Simon J.; Hill, Adrian V.S.; O’Mahony, Conor; Crean, Abina M.; Moore, Anne C.

    2016-01-01

    Vaccines are sensitive biologics that require continuous refrigerated storage to maintain their viability. The vast majority of vaccines are also administered using needles and syringes. The need for cold chain storage and the significant logistics surrounding needle-and-syringe vaccination is constraining the success of immunization programs. Recombinant live viral vectors are a promising platform for the development of vaccines against a number of infectious diseases, however these viruses must retain infectivity to be effective. Microneedles offer an effective and painless method for delivery of vaccines directly into skin that in the future could provide solutions to current vaccination issues. Here we investigated methods of coating live recombinant adenovirus and modified vaccinia virus Ankara (MVA) vectors onto solid microneedle arrays. An effective spray-coating method, using conventional pharmaceutical processes, was developed, in tandem with suitable sugar-based formulations, which produces arrays with a unique coating of viable virus in a dry form around the shaft of each microneedle on the array. Administration of live virus-coated microneedle arrays successfully resulted in virus delivery, transcutaneous infection and induced an antibody or CD8+ T cell response in mice that was comparable to that obtained by needle-and-syringe intradermal immunization. To our knowledge, this is the first report of successful vaccination with recombinant live viral vectored vaccines coated on microneedle delivery devices. PMID:22245683

  15. Coated microneedle arrays for transcutaneous delivery of live virus vaccines.

    PubMed

    Vrdoljak, Anto; McGrath, Marie G; Carey, John B; Draper, Simon J; Hill, Adrian V S; O'Mahony, Conor; Crean, Abina M; Moore, Anne C

    2012-04-10

    Vaccines are sensitive biologics that require continuous refrigerated storage to maintain their viability. The vast majority of vaccines are also administered using needles and syringes. The need for cold chain storage and the significant logistics surrounding needle-and-syringe vaccination is constraining the success of immunization programs. Recombinant live viral vectors are a promising platform for the development of vaccines against a number of infectious diseases, however these viruses must retain infectivity to be effective. Microneedles offer an effective and painless method for delivery of vaccines directly into skin that in the future could provide solutions to current vaccination issues. Here we investigated methods of coating live recombinant adenovirus and modified vaccinia virus Ankara (MVA) vectors onto solid microneedle arrays. An effective spray-coating method, using conventional pharmaceutical processes, was developed, in tandem with suitable sugar-based formulations, which produces arrays with a unique coating of viable virus in a dry form around the shaft of each microneedle on the array. Administration of live virus-coated microneedle arrays successfully resulted in virus delivery, transcutaneous infection and induced an antibody or CD8(+) T cell response in mice that was comparable to that obtained by needle-and-syringe intradermal immunization. To our knowledge, this is the first report of successful vaccination with recombinant live viral vectored vaccines coated on microneedle delivery devices. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. In vivo evaluation of a nasal insulin delivery system based on thiolated chitosan.

    PubMed

    Krauland, Alexander H; Leitner, Verena M; Grabovac, Vjera; Bernkop-Schnürch, Andreas

    2006-11-01

    The aim of this study was the preparation and in vivo evaluation of a nasal insulin delivery system based on thiolated chitosan. 2-Iminothiolane was covalently attached to chitosan. The resulting conjugate (chitosan-TBA) exhibited 304.9 +/- 63.5 micromol thiol groups per gram polymer. Microparticles were prepared via a new precipitation-micronization technique. The microparticulate delivery system comprised insulin, reduced glutathione and chitosan-TBA (Chito-TBA/Ins) or unmodified chitosan (Chito/Ins) and control microparticles were composed of insulin and mannitol (Mannitol/Ins). Due to a hydration process the size of Chito-TBA/Ins and Chito/Ins microparticles increased in phosphate buffer pH 6.8 2.6- and 2.2-fold, respectively. Fluorescent-labeled insulin-loaded chitosan-TBA microparticles showed a controlled release over 4 h. Chito-TBA/Ins administered nasally to rats led to an absolute bioavailability of 6.9 +/- 1.5%. The blood glucose level decreased for more than 2 h and the calculated absolute pharmacological efficacy was 4.9 +/- 1.4%. Chito/Ins, in comparison, displayed a bioavailability of 4.2 +/- 1.8% and a pharmacological efficacy of 0.7 +/- 0.6%. Mannitol/Ins showed a bioavailability of 1.6 +/- 0.4% and no reduction of the blood glucose level at all. According to these findings microparticles comprising chitosan-TBA seem to have substantial higher potential for nasal insulin administration than unmodified chitosan. Copyright 2006 Wiley-Liss, Inc. and the American Pharmacists Association

  17. Particulate delivery systems for vaccination against bioterrorism agents and emerging infectious pathogens

    PubMed Central

    Fan, Yuchen; Moon, James J.

    2016-01-01

    Bioterrorism agents that can be easily transmitted with high mortality rates and cause debilitating diseases pose major threats to national security and public health. The recent Ebola virus outbreak in West Africa and ongoing Zika virus outbreak in Brazil, now spreading throughout Latin America, are case examples of emerging infectious pathogens that have incited widespread fear and economic and social disruption on a global scale. Prophylactic vaccines would provide effective countermeasures against infectious pathogens and biological warfare agents. However, traditional approaches relying on attenuated or inactivated vaccines have been hampered by their unacceptable levels of reactogenicity and safety issues, whereas subunit antigen-based vaccines suffer from suboptimal immunogenicity and efficacy. In contrast, particulate vaccine delivery systems offer key advantages, including efficient and stable delivery of subunit antigens, co-delivery of adjuvant molecules to bolster immune responses, low reactogenicity due to the use of biocompatible biomaterials, and robust efficiency to elicit humoral and cellular immunity in systemic and mucosal tissues. Thus, vaccine nanoparticles and microparticles are promising platforms for clinical development of biodefense vaccines. In this review, we summarize the current status of research efforts to develop particulate vaccine delivery systems against bioterrorism agents and emerging infectious pathogens. PMID:27038091

  18. Evaluation of synthetic infection-enhancing lipopeptides as adjuvants for a live-attenuated canine distemper virus vaccine administered intra-nasally to ferrets.

    PubMed

    Nguyen, D Tien; Ludlow, Martin; van Amerongen, Geert; de Vries, Rory D; Yüksel, Selma; Verburgh, R Joyce; Osterhaus, Albert D M E; Duprex, W Paul; de Swart, Rik L

    2012-07-20

    Inactivated paramyxovirus vaccines have been associated with hypersensitivity responses upon challenge infection. For measles and canine distemper virus (CDV) safe and effective live-attenuated virus vaccines are available, but for human respiratory syncytial virus and human metapneumovirus development of such vaccines has proven difficult. We recently identified three synthetic bacterial lipopeptides that enhance paramyxovirus infections in vitro, and hypothesized these could be used as adjuvants to promote immune responses induced by live-attenuated paramyxovirus vaccines. Here, we tested this hypothesis using a CDV vaccination and challenge model in ferrets. Three groups of six animals were intra-nasally vaccinated with recombinant (r) CDV(5804P)L(CCEGFPC) in the presence or absence of the infection-enhancing lipopeptides Pam3CSK4 or PHCSK4. The recombinant CDV vaccine virus had previously been described to be over-attenuated in ferrets. A group of six animals was mock-vaccinated as control. Six weeks after vaccination all animals were challenged with a lethal dose of rCDV strain Snyder-Hill expressing the red fluorescent protein dTomato. Unexpectedly, intra-nasal vaccination of ferrets with rCDV(5804P)L(CCEGFPC) in the absence of lipopeptides resulted in good immune responses and protection against lethal challenge infection. However, in animals vaccinated with lipopeptide-adjuvanted virus significantly higher vaccine virus loads were detected in nasopharyngeal lavages and peripheral blood mononuclear cells. In addition, these animals developed significantly higher CDV neutralizing antibody titers compared to animals vaccinated with non-adjuvanted vaccine. This study demonstrates that the synthetic cationic lipopeptides Pam3CSK4 and PHCSK4 not only enhance paramyxovirus infection in vitro, but also in vivo. Given the observed enhancement of immunogenicity their potential as adjuvants for other live-attenuated paramyxovirus vaccines should be considered

  19. The success of microneedle-mediated vaccine delivery into skin

    PubMed Central

    Marshall, Sarah; Sahm, Laura J.; Moore, Anne C.

    2016-01-01

    ABSTRACT Microneedles (MNs) are designed to specifically target the outermost, skin barrier layer, the stratum corneum, creating transient pathways for minimally invasive transcutaneous delivery. It is reported that MNs can facilitate delivery without stimulating the pain receptors or damaging blood vessels that lie beneath, thus being perceived as painless and associated with reduced bleeding. This immunocompetence of the skin, coupled with its ease of access, makes this organ an attractive vaccination site. The purpose of this review was to collate primary scientific literature pertaining to MN-mediated in vivo vaccination programmes. A total of 62 original research articles are presented, compiling vaccination strategies in 6 different models (mouse, rat, guinea pig, rabbit, pig, macaque and human). Vaccines tested span a wide range of viral, bacterial and protozoan pathogens and includes 7 of the 13 vaccine-preventable diseases, as defined by the WHO. This review highlights the paucity of available clinical trial data. MN-delivered vaccines have demonstrated safety and immunogenicity in pre-clinical models and boast desirable attributes such as painless administration, thermostability, dose-sparing capacity and the potential for self-administration. These advantages should contribute to enhanced global vaccine access. PMID:27050528

  20. Influenza vaccine delivery delays from the perspective of primary care physicians.

    PubMed

    O'Leary, Sean T; Barrow, Jennifer C; McQuillan, Lon; Daley, Matthew F; Crane, Lori A; Beaty, Brenda L; Babbel, Christine I; Dickinson, L Miriam; Kempe, Allison

    2011-06-01

    The effects of delayed influenza vaccine delivery on primary practices are currently unknown. To describe, among primary care physicians nationally regarding the 2006-2007 influenza season: (1) how physicians defined influenza vaccine delay; (2) the extent of reported vaccine delays; and (3) the perceived effects of vaccine delays. Between March and June 2007, a total of 1268 primary care physicians nationally were surveyed. Survey response was 74% (n=940). The majority of physicians (79%) defined "influenza vaccine delay" as not receiving vaccine by November 1. Fifty-three percent reported a vaccine delay. Providers reported the following as effects of delays: reduced satisfaction of patients or parents in the practice (72%); decreased percentage in their practice who received the vaccination (65%); disruption of scheduling influenza clinics (55%); increased referral of patients elsewhere for vaccination (55%); and negative financial impact caused by unused vaccine (46%). Those who reported experiencing delays more often reported not meeting demand for vaccine (adjusted risk ratio [ARR]=1.83, 95% CI=1.64, 2.07); that grocery stores, retail outlets, or pharmacies had vaccine before their practices did (ARR=1.82, 95% CI=1.53, 2.26); not receiving all vaccine that was ordered (ARR=1.19, 95% CI=1.06, 1.36); and having leftover vaccine (ARR=1.17, 95% CI=1.04, 1.32). During the 2006-2007 influenza season, a non-shortage season, the majority of respondents reported experiencing an influenza vaccine delivery delay. Experiencing a delay was thought to decrease vaccination use, increase referrals elsewhere, and have a negative financial impact on practices. Delayed delivery of influenza vaccine is disruptive for primary care practices, and it consequently may affect vaccination coverage. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  1. Needle-free nasal delivery of glucagon for treatment of diabetes-related severe hypoglycemia: toxicology of polypropylene resin used in delivery device.

    PubMed

    Reno, Frederick E; Edwards, C Nicholas; Bendix Jensen, Morten; Török-Bathó, Magdolna; Esdaile, David J; Piché, Claude; Triest, Myriam; Carballo, Dolorès

    2016-09-01

    The intranasal route is a promising route of administration for several emergency rescue drugs including naloxone and glucagon. Glucagon nasal powder (GNP) is a novel, needle-free delivery system for intranasal administration of glucagon for the treatment of severe hypoglycemia, an infrequent but serious complication of insulin use in patients with diabetes. The GNP delivery device is a compact, highly portable, single-use nasal powder dosing device constructed of polypropylene that allows for simple, single-step administration. To evaluate the toxicological profile of the polypropylene resin used in the actuator part of the delivery device that will contact skin and nasal mucosal membranes of the patient, we performed an in vitro cytotoxicity study, a skin sensitization study and an irritation (intracutaneous reactivity) study in animal models. Extracts of the actuator of the GNP device were generated from HAM F12 medium with 10% fetal bovine serum, 0.9% sodium chloride (NaCl) or sesame oil. The in vitro cytotoxicity test was performed in cultured L929 mouse fibroblasts. Skin sensitization analysis was performed in 10 guinea pigs according to the Magnusson-Kligman method, using a maximization method with Freund's Complete Adjuvant. Irritation following intracutaneous/intradermal treatment with device extracts (NaCl and sesame oil extractants) was assessed in three New Zealand White rabbits. In vitro cytotoxicity test: Both undiluted and diluted extract showed no toxicity (i.e. no abnormal morphology, cell death or cell lysis) toward L929 fibroblasts (cytotoxicity grade 0). Sensitization test in guinea pigs: Challenge with device extracts did not evoke positive responses in test animals previously induced with device extracts. The net response value represented an incidence rate of 0% and a net dermal irritation score value of 0.00. Irritation (intracutaneous/intradermal) test in New Zealand White rabbits: Device extracts and corresponding vehicle controls caused

  2. Preventative vaccine-loaded mannosylated chitosan nanoparticles intended for nasal mucosal delivery enhance immune responses and potent tumor immunity.

    PubMed

    Yao, Wenjun; Peng, Yixing; Du, Mingzhu; Luo, Juan; Zong, Li

    2013-08-05

    Chitosan (CS) has been extensively used as a protein drug and gene delivery carrier, but its delivery efficiency is unsatisfactory. In this study, a mannose ligand was used to modify CS, which could enhance the delivery efficiency of CS via mannose receptor-mediated endocytosis. A preventative anti-GRP DNA vaccine (pCR3.1-VS-HSP65-TP-GRP6-M2, pGRP) was condensed with mannosylated chitosan (MCS) to form MCS/pGRP nanoparticles. Nanoparticles were intranasally administered in a subcutaneous mice prostate carcinoma model to evaluate the efficacy on inhibition of the growth of tumor cells. The titers of anti-GRP IgG that lasted for 11 weeks were significantly higher than that for administration of CS/pGRP nanoparticles (p < 0.01) and intramuscular administration of a pGRP solution (p < 0.05) to mice. In addition, immunization with MCS/pGRP nanoparticles could suppress the growth of tumor cells. The average tumor weight (0.79 ± 0.30 g) was significantly lower than that in the CS/pGRP nanoparticle group (1.69 ± 0.15 g) (p < 0.01) or that in the pGRP group (1.12 ± 0.37 g) (p < 0.05). Cell binding and cellular uptake results indicated that MCS/pGRP nanoparticles bound with C-type lectin receptors on macrophages. MCS was an efficient targeting gene delivery carrier and could be used in antitumor immunotherapy.

  3. Delivery of Vaccines By Biodegradable Polymeric Microcapsules with Bioadherence Properties. Phase 1.

    DTIC Science & Technology

    1995-10-01

    DAMD17-95-C-5061 TITLE: Delivery of Vaccines by Biodegradable Polymeric Microcapsules with Bioadherence Properties PRINCIPAL INVESTIGATOR: Robert L...SUBTITLE 5. FUNDING NUMBERS Delivery of Vaccines By Biodegradable Polymeric Microcapsules with Bioadherence Properties DAMD17-95-C-5061 6. AUTHOR(S...SUBJECT TERMS 15. NUMBER OF PAGES Polymer microspheres 27 Microencapsulated vaccines 16. PRICE CODE 17. SECURITY CLASSIFICATION 18. SECURITY

  4. Phenotype and function of nasal dendritic cells

    PubMed Central

    Lee, Haekyung; Ruane, Darren; Law, Kenneth; Ho, Yan; Garg, Aakash; Rahman, Adeeb; Esterházy, Daria; Cheong, Cheolho; Goljo, Erden; Sikora, Andrew G.; Mucida, Daniel; Chen, Benjamin; Govindraj, Satish; Breton, Gaëlle; Mehandru, Saurabh

    2015-01-01

    Intranasal vaccination generates immunity across local, regional and distant sites. However, nasal dendritic cells (DC), pivotal for the induction of intranasal vaccine- induced immune responses, have not been studied in detail. Here, using a variety of parameters, we define nasal DCs in mice and humans. Distinct subsets of “classical” DCs, dependent on the transcription factor zbtb46 were identified in the murine nose. The murine nasal DCs were FLT3 ligand-responsive and displayed unique phenotypic and functional characteristics including the ability to present antigen, induce an allogeneic T cell response and migrate in response to LPS or live bacterial pathogens. Importantly, in a cohort of human volunteers, BDCA-1+ DCs were observed to be the dominant nasal DC population at steady state. During chronic inflammation, the frequency of both BDCA-1+ and BDCA-3hi DCs was reduced in the nasal tissue, associating the loss of these immune sentinels with chronic nasal inflammation. The present study is the first detailed description of the phenotypic, ontogenetic and functional properties of nasal DCs and will inform the design of preventative immunization strategies as well as therapeutic modalities against chronic rhinosinusitis. PMID:25669151

  5. Formulation and delivery of vaccines: Ongoing challenges for animal management

    PubMed Central

    Sharma, Sameer; Hinds, Lyn A.

    2012-01-01

    Development of a commercially successful animal vaccine is not only influenced by various immunological factors, such as type of antigen but also by formulation and delivery aspects. The latter includes the need for a vector or specific delivery system, the choice of route of administration and the nature of the target animal population and their habitat. This review describes the formulation and delivery aspects of various types of antigens such as killed microorganisms, proteins and nucleic acids for the development of efficacious and safe animal vaccines. It also focuses on the challenges associated with the different approaches that might be required for formulating and delivering species specific vaccines, particularly if their intended use is for improved animal management with respect to disease and/or reproductive control. PMID:23248557

  6. Nasal deposition and clearance in man: comparison of a bidirectional powder device and a traditional liquid spray pump.

    PubMed

    Djupesland, Per Gisle; Skretting, Arne

    2012-10-01

    Delivery of powder formulations to the nose is an attractive alternative for many drugs and vaccines. This study compared the regional nasal deposition and clearance patterns of lactose powder delivered by the OptiNose powder device (Opt-Powder; OptiNose US Inc., Yardley, PA, USA) to that of liquid aerosol administered via a traditional hand-actuated liquid spray pump (Rexam SP270, Rexam Pharma, France). The study was an open-label, crossover design in seven healthy subjects (five females, two males). The regional nasal deposition and clearance patterns of the Opt-Powder device were compared to a traditional liquid spray pump by dynamic gamma camera imaging after administration of either (99m)Tc-labeled lactose powder or liquid (99m)Tc- diethelyne triamine pentaacetic acid-aerosol. The gamma camera images were scaled and aligned with sagittal magnetic resonance images to identify nasal regions. Possible deposition of radiolabeled material in the lungs following both methods of delivery was also evaluated. Both powder and spray were distributed to all of the nasal regions. The Opt-Powder device, however, achieved significantly larger initial deposition in the upper and middle posterior regions of the nose than spray (upper posterior region; Opt-Powder 18.3% ± 11.5 vs. Spray 2.4% ± 1.8, p<0.02; sum of upper and middle posterior regions; Opt-Powder 53.5% ± 18.5 vs. Spray 15.7% ± 13.8, p<0.02). The summed initial deposition to the lower anterior and posterior regions for spray was three times higher compared to Opt-Powder (Opt-Powder 17.4% ± 24.5 vs. Spray 59.4% ± 18.2, p<0.04). OptiNose powder delivery resulted in more rapid overall nasal clearance. No lung deposition was observed. The initial deposition following powder delivery was significantly larger in the ciliated mucosa of the upper and posterior nasal regions, whereas less was deposited in the lower regions. Overall nasal clearance of powder was slower initially, but due to retention in anterior

  7. Delivery of Oxytocin to the Brain for the Treatment of Autism Spectrum Disorder by Nasal Application.

    PubMed

    Tanaka, Akiko; Furubayashi, Tomoyuki; Arai, Mari; Inoue, Daisuke; Kimura, Shunsuke; Kiriyama, Akiko; Kusamori, Kosuke; Katsumi, Hidemasa; Yutani, Reiko; Sakane, Toshiyasu; Yamamoto, Akira

    2018-03-05

    Oxytocin (OXT) is a cyclic nonapeptide, two amino acids of which are cysteine, forming an intramolecular disulfide bond. OXT is produced in the hypothalamus and is secreted into the bloodstream from the posterior pituitary. As recent studies have suggested that OXT is a neurotransmitter exhibiting central effects important for social deficits, it has drawn much attention as a drug candidate for the treatment of autism. Although human-stage clinical trials of the nasal spray of OXT for the treatment of autism have already begun, few studies have examined the pharmacokinetics and brain distribution of OXT after nasal application. The aim of this study is to evaluate the disposition, nasal absorption, and therapeutic potential of OXT after nasal administration. The pharmacokinetics of OXT after intravenous bolus injection to rats followed a two-compartment model, with a rapid initial half-life of 3 min. The nasal bioavailability of OXT was approximately 2%. The brain concentration of OXT after nasal application was much higher than that after intravenous application, despite much lower concentrations in the plasma. More than 95% of OXT in the brain was directly transported from the nasal cavity. The in vivo stress-relief effect by OXT was observed only after intranasal administration. These results indicate that pharmacologically active OXT was effectively delivered to the brain after intranasal administration. In conclusion, the nasal cavity is a promising route for the efficient delivery of OXT to the brain.

  8. Delivery cost of human papillomavirus vaccination of young adolescent girls in Peru, Uganda and Viet Nam.

    PubMed

    Levin, Carol E; Van Minh, Hoang; Odaga, John; Rout, Swampa Sarit; Ngoc, Diep Nguyen Thi; Menezes, Lysander; Araujo, Maria Ana Mendoza; LaMontagne, D Scott

    2013-08-01

    To estimate the incremental delivery cost of human papillomavirus (HPV) vaccination of young adolescent girls in Peru, Uganda and Viet Nam. Data were collected from a sample of facilities that participated in five demonstration projects for hpv vaccine delivery: school-based delivery was used in Peru, Uganda and Viet Nam; health-centre-based delivery was also used in Viet Nam; and integrated delivery, which involved existing health services, was also used in Uganda. Microcosting methods were used to guide data collection on the use of resources (i.e. staff, supplies and equipment) and data were obtained from government, demonstration project and health centre administrative records. Delivery costs were expressed in 2009 United States dollars (US$). Exclusively project-related expenses and the cost of the vaccine were excluded. The economic delivery cost per vaccine dose ranged from US$ 1.44 for integrated outreach in Uganda to US$ 3.88 for school-based delivery in Peru. In Viet Nam, the lowest cost per dose was US$ 1.92 for health-centre-based delivery. Cost profiles revealed that, in general, the largest contributing factors were project start-up costs and recurrent personnel costs. The delivery cost of HPV vaccine was higher than published costs for traditional vaccines recommended by the Expanded Programme on Immunization (EPI). The cost of delivering HPV vaccine to young adolescent girls in Peru, Uganda and Viet Nam was higher than that for vaccines currently in the EPI schedule. The cost per vaccine dose was lower when delivery was integrated into existing health services.

  9. Stabilization of Influenza Vaccine Enhances Protection by Microneedle Delivery in the Mouse Skin

    PubMed Central

    Yoo, Dae-Goon; Compans, Richard W.; Prausnitz, Mark R.; Kang, Sang-Moo

    2009-01-01

    Background Simple and effective vaccine administration is particularly important for annually recommended influenza vaccination. We hypothesized that vaccine delivery to the skin using a patch containing vaccine-coated microneedles could be an attractive approach to improve influenza vaccination compliance and efficacy. Methodology/Principal Findings Solid microneedle arrays coated with inactivated influenza vaccine were prepared for simple vaccine delivery to the skin. However, the stability of the influenza vaccine, as measured by hemagglutination activity, was found to be significantly damaged during microneedle coating. The addition of trehalose to the microneedle coating formulation retained hemagglutination activity, indicating stabilization of the coated influenza vaccine. For both intramuscular and microneedle skin immunization, delivery of un-stabilized vaccine yielded weaker protective immune responses including viral neutralizing antibodies, protective efficacies, and recall immune responses to influenza virus. Immunization using un-stabilized vaccine also shifted the pattern of antibody isotypes compared to the stabilized vaccine. Importantly, a single microneedle-based vaccination using stabilized influenza vaccine was found to be superior to intramuscular immunization in controlling virus replication as well as in inducing rapid recall immune responses post challenge. Conclusions/Significance The functional integrity of hemagglutinin is associated with inducing improved protective immunity against influenza. Simple microneedle influenza vaccination in the skin produced superior protection compared to conventional intramuscular immunization. This approach is likely to be applicable to other vaccines too. PMID:19779615

  10. Delivery cost of human papillomavirus vaccination of young adolescent girls in Peru, Uganda and Viet Nam

    PubMed Central

    Van Minh, Hoang; Odaga, John; Rout, Swampa Sarit; Ngoc, Diep Nguyen Thi; Menezes, Lysander; Araujo, Maria Ana Mendoza; LaMontagne, D Scott

    2013-01-01

    Abstract Objective To estimate the incremental delivery cost of human papillomavirus (HPV) vaccination of young adolescent girls in Peru, Uganda and Viet Nam. Methods Data were collected from a sample of facilities that participated in five demonstration projects for HPV vaccine delivery: school-based delivery was used in Peru, Uganda and Viet Nam; health-centre-based delivery was also used in Viet Nam; and integrated delivery, which involved existing health services, was also used in Uganda. Microcosting methods were used to guide data collection on the use of resources (i.e. staff, supplies and equipment) and data were obtained from government, demonstration project and health centre administrative records. Delivery costs were expressed in 2009 United States dollars (US$). Exclusively project-related expenses and the cost of the vaccine were excluded. Findings The economic delivery cost per vaccine dose ranged from US$ 1.44 for integrated outreach in Uganda to US$ 3.88 for school-based delivery in Peru. In Viet Nam, the lowest cost per dose was US$ 1.92 for health-centre-based delivery. Cost profiles revealed that, in general, the largest contributing factors were project start-up costs and recurrent personnel costs. The delivery cost of HPV vaccine was higher than published costs for traditional vaccines recommended by the Expanded Programme on Immunization (EPI). Conclusion The cost of delivering HPV vaccine to young adolescent girls in Peru, Uganda and Viet Nam was higher than that for vaccines currently in the EPI schedule. The cost per vaccine dose was lower when delivery was integrated into existing health services. PMID:23940406

  11. Dendritic cell targeted chitosan nanoparticles for nasal DNA immunization against SARS CoV nucleocapsid protein.

    PubMed

    Raghuwanshi, Dharmendra; Mishra, Vivek; Das, Dipankar; Kaur, Kamaljit; Suresh, Mavanur R

    2012-04-02

    This work investigates the formulation and in vivo efficacy of dendritic cell (DC) targeted plasmid DNA loaded biotinylated chitosan nanoparticles for nasal immunization against nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) as antigen. The induction of antigen-specific mucosal and systemic immune response at the site of virus entry is a major challenge for vaccine design. Here, we designed a strategy for noninvasive receptor mediated gene delivery to nasal resident DCs. The pDNA loaded biotinylated chitosan nanoparticles were prepared using a complex coacervation process and characterized for size, shape, surface charge, plasmid DNA loading and protection against nuclease digestion. The pDNA loaded biotinylated chitosan nanoparticles were targeted with bifunctional fusion protein (bfFp) vector for achieving DC selective targeting. The bfFp is a recombinant fusion protein consisting of truncated core-streptavidin fused with anti-DEC-205 single chain antibody (scFv). The core-streptavidin arm of fusion protein binds with biotinylated nanoparticles, while anti-DEC-205 scFv imparts targeting specificity to DC DEC-205 receptor. We demonstrate that intranasal administration of bfFp targeted formulations along with anti-CD40 DC maturation stimuli enhanced magnitude of mucosal IgA as well as systemic IgG against N protein. The strategy led to the detection of augmented levels of N protein specific systemic IgG and nasal IgA antibodies. However, following intranasal delivery of naked pDNA no mucosal and systemic immune responses were detected. A parallel comparison of targeted formulations using intramuscular and intranasal routes showed that the intramuscular route is superior for induction of systemic IgG responses compared with the intranasal route. Our results suggest that targeted pDNA delivery through a noninvasive intranasal route can be a strategy for designing low-dose vaccines.

  12. [Preparation of freeze-dried powder of recombinate hirudin-2 nanoparticle for nasal delivery and permeability through nasal membrane in vitro].

    PubMed

    Chen, Ming-Xia; Zhang, Jian-Bao; Yu, Ji-Ping; Ye, Jing; Wei, Bao-Hong; Zhang, Yu-Jie

    2013-06-01

    To optimize the freeze-dried powder preparation technology of recombinate hirudin-2 (rHV2) nanoparticle which has bio-adhesive characteristic for nasal delivery, also to investigate its stability and permeability through nasal membrane in vitro. Taking the appearance, rediffusion of nanoparticle and rHV2 encapsulation efficiency as the evaluation indexes. Cryoprotector, the preparative technique and the effect of illumination and high temperature factors on its stability for rHV2 freeze-dried powder were investigated. Using Fraze diffusion cell technique, the permeability of rHV2 across rabbit nasal mucous membrane in chitosan solution, chitosan nanoparticle, and nanoparticle frozen-dried powder were compared with that in normal saline solution. The optimized preparation of rHV2 nanoparticle freeze-dried powder was as follows: 5% trehalose and glucose (1:1) was used as cryoprotector, nanoparticle solution was freezed for 24 h in vacuum frozen-dryer after being pre-freezed for 24 h. The content of rHV2 in the freeze-dried powder was 1.1 ug/mg. Illumination had little effect on the appearance, rediffusion and encapsulation efficiency of the rHV2 freeze-dried powder. High temperature could obviously influence the appearance of nanoparticle freeze-dried powder. The permeability coefficient (P) of nanoparticle was 5 times more than that in chictonson solution. It was indicated that chitosan nanoparticle has effect on increasing the permeability of rHV2. The freeze-dried powder of chitosan nanoparticle can be a good nasal preparation of rHV2.

  13. The growth of retail clinics in vaccination delivery in the U.S.

    PubMed

    Uscher-Pines, Lori; Harris, Katherine M; Burns, Rachel M; Mehrotra, Ateev

    2012-07-01

    Retail clinics are a promising venue in which to promote and administer vaccinations; however, little is known about who receives vaccinations at a retail clinic. The aim of this paper was to describe the use of retail clinics in the delivery of recommended vaccinations. The three largest retail clinic operators in the U.S.--MinuteClinic, TakeCare, and LittleClinic--provided de-identified clinic data for 2007-2009. Descriptive statistics were generated in 2011 on visit type, type of vaccination, patient age, and payment method. From 2007 to 2009, there were 8.9 million retail clinic visits across the three largest clinic operators. In 2009, vaccinations were administered at 1,952,610 visits, up from 469,330 visits in 2007. Visits in which vaccinations were administered accounted for 39.9%, 36.4%, and 42.0% of total visits in 2007, 2008, and 2009, respectively. In 2009, 1.8 million influenza vaccinations (including seasonal and H1N1 vaccinations) were administered by the two largest retail clinic operators (94% of all vaccination visits). Pneumococcal vaccination was administered at 59,849 visits (3% of all vaccination visits). In 2009, vaccinations were also administered in 0.8% of acute care visits (n=18,807); 0.8% of chronic care visits (n=261); and 1.3% of general medical exams (n=2497). Results suggest that retail clinics play a growing role in vaccination delivery, and vaccinations constitute a substantial share of the business conducted by retail clinics. As such, retail clinics have the potential to play an important role in vaccination delivery in the U.S. Retail clinics potentially could deliver more vaccinations if they reviewed vaccination histories and counseled patients regarding the benefits of vaccination during acute care visits. Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  14. Human and Animal Vaccination Delivery to Remote Nomadic Families, Chad

    PubMed Central

    Bechir, Mahamat; Ahmed, Mahamat Abdoulaye; Wyss, Kaspar; Randolph, Thomas F.; Zinsstag, Jakob

    2007-01-01

    Vaccination services for people and livestock often fail to achieve sufficient coverages in Africa’s remote rural settings because of financial, logistic, and service delivery constraints. In Chad from 2000 through 2005, we demonstrated the feasibility of combining vaccination programs for nomadic pastoralists and their livestock. Sharing of transport logistics and equipment between physicians and veterinarians reduced total costs. Joint delivery of human and animal health services is adapted to and highly valued by hard-to-reach pastoralists. In intervention zones, for the first time ≈10% of nomadic children (>1–11 months of age) were fully immunized annually and more children and women were vaccinated per day during joint vaccination rounds than during vaccination of persons only and not their livestock (130 vs. 100, p<0.001). By optimizing use of limited logistical and human resources, public health and veterinary services both become more effective, especially at the district level. PMID:17552089

  15. Seasonal influenza vaccination delivery through community pharmacists in England: evaluation of the London pilot

    PubMed Central

    Atkins, Katherine; van Hoek, Albert Jan; Watson, Conall; Baguelin, Marc; Choga, Lethiwe; Patel, Anika; Raj, Thara; Jit, Mark; Griffiths, Ulla

    2016-01-01

    Objective To evaluate the effectiveness and cost of the pan-London pharmacy initiative, a programme that allows administration of seasonal influenza vaccination to eligible patients at pharmacies. Design We analysed 2013–2015 data on vaccination uptake in pharmacies via the Sonar reporting system, and the total vaccination uptake via 2011–2015 ImmForm general practitioner (GP) reporting system data. We conducted an online survey of London pharmacists who participate in the programme to assess time use data, vaccine choice, investment costs and opinions about the programme. We conducted an online survey of London GPs to assess vaccine choice of vaccine and opinions about the pharmacy vaccine delivery programme. Setting All London boroughs. Participants London-based GPs, and pharmacies that currently offer seasonal flu vaccination. Interventions Not applicable. Main outcome measures Comparison of annual vaccine uptake in London across risk groups from years before pharmacy vaccination introduction to after pharmacy vaccination introduction. Completeness of vaccine uptake reporting data. Cost to the National Health Service (NHS) of flu vaccine delivery at pharmacies with that at GPs. Cost to pharmacists of flu delivery. Opinions of pharmacists and GPs regarding the flu vaccine pharmacy initiative. Results No significant change in the uptake of seasonal vaccination in any of the risk groups as a result of the pharmacy initiative. While on average a pharmacy-administered flu vaccine dose costs the NHS up to £2.35 less than a dose administered at a GP, a comparison of the 2 recording systems suggests there is substantial loss of data. Conclusions Flu vaccine delivery through pharmacies shows potential for improving convenience for vaccine recipients. However, there is no evidence that vaccination uptake increases and the use of 2 separate recording systems leads to time-consuming data entry and missing vaccine record data. PMID:26883237

  16. Adenovirus F protein as a delivery vehicle for botulinum B

    PubMed Central

    2010-01-01

    Background Immunization with recombinant carboxyl-terminal domain of the heavy chain (Hc domain) of botulinum neurotoxin (BoNT) stimulates protective immunity against native BoNT challenge. Most studies developing a botulism vaccine have focused on the whole Hc; however, since the principal protective epitopes are located within β-trefoil domain (Hcβtre), we hypothesize that immunization with the Hcβtre domain is sufficient to confer protective immunity. In addition, enhancing its uptake subsequent to nasal delivery prompted development of an alternative vaccine strategy, and we hypothesize that the addition of targeting moiety adenovirus 2 fiber protein (Ad2F) may enhance such uptake during vaccination. Results The Hcβtre serotype B immunogen was genetically fused to Ad2F (Hcβtre/B-Ad2F), and its immunogenicity was tested in mice. In combination with the mucosal adjuvant, cholera toxin (CT), enhanced mucosal IgA and serum IgG Ab titers were induced by nasal Hcβtre-Ad2F relative to Hcβtre alone; however, similar Ab titers were obtained upon intramuscular immunization. These BoNT/B-specific Abs induced by nasal immunization were generally supported in large part by Th2 cells, as opposed to Hcβtre-immunized mice that showed more mixed Th1 and Th2 cells. Using a mouse neutralization assay, sera from animals immunized with Hcβtre and Hcβtre-Ad2F protected mice against 2.0 LD50. Conclusion These results demonstrate that Hcβtre-based immunogens are highly immunogenic, especially when genetically fused to Ad2F, and Ad2F can be exploited as a vaccine delivery platform to the mucosa. PMID:20609248

  17. Drug delivery in overcoming the blood–brain barrier: role of nasal mucosal grafting

    PubMed Central

    Marianecci, Carlotta; Rinaldi, Federica; Hanieh, Patrizia Nadia; Di Marzio, Luisa; Paolino, Donatella; Carafa, Maria

    2017-01-01

    The blood–brain barrier (BBB) plays a fundamental role in protecting and maintaining the homeostasis of the brain. For this reason, drug delivery to the brain is much more difficult than that to other compartments of the body. In order to bypass or cross the BBB, many strategies have been developed: invasive techniques, such as temporary disruption of the BBB or direct intraventricular and intracerebral administration of the drug, as well as noninvasive techniques. Preliminary results, reported in the large number of studies on the potential strategies for brain delivery, are encouraging, but it is far too early to draw any conclusion about the actual use of these therapeutic approaches. Among the most recent, but still pioneering, approaches related to the nasal mucosa properties, the permeabilization of the BBB via nasal mucosal engrafting can offer new potential opportunities. It should be emphasized that this surgical procedure is quite invasive, but the implication for patient outcome needs to be compared to the gold standard of direct intracranial injection, and evaluated whilst keeping in mind that central nervous system diseases and lysosomal storage diseases are chronic and severely debilitating and that up to now no therapy seems to be completely successful. PMID:28184152

  18. Preparation and brain delivery of nasal solid lipid nanoparticles of quetiapine fumarate in situ gel in rat model of schizophrenia

    PubMed Central

    Li, Jian-Chun; Zhang, Wen-Jing; Zhu, Jin-Xiu; Zhu, Na; Zhang, Hong-Min; Wang, Xiu; Zhang, Jin; Wang, Qing-Qing

    2015-01-01

    To investigate the brain delivery in rat by nasal Quetiapine fumarate (QF) loaded with solid lipid nanoparticles in situ gel (QF-SLN-gel). QF-SLN-gel was prepared through micro-emulsion technique. The rat model of schizophrenia was established by intraperitoneal injection of (+)-MK-801, evaluated by stereotypic behavior, Mori’s Water Maze (MWM) test and hematoxylin and eosin (HE) staining of hippocampus. The animals were administrated with QF via oral, nasal or tail vein approach and the concentration of QF in blood and brain was determined using high performance liquid chromatography (HPLC). The QF-SLN-gel was even and transparent, having size of 117.8±2.67 d.nm, potential of 57.2±0.24 mV and EF of 97.6±0.58%. After administration of QF-SLN-gel, the concentration of QF in blood and brain of rats in nasal QF-SLN-gel group was similar with that of rats in tail vein QF group, but significantly higher than that of rats in oral QF group. The hippocampal morphology changes induced by (+)-MK-801 were ameliorated by QF, with advantage of nasal QF-SLN-gel over tail vein QF. The nasal QF-SLN-gel had stable and good brain delivery and could ameliorate the damages in rat model of schizophrenia induced by (+)-MK-801. PMID:26770349

  19. Polymeric nanoparticles: potent vectors for vaccine delivery targeting cancer and infectious diseases.

    PubMed

    Bolhassani, Azam; Javanzad, Shabnam; Saleh, Tayebeh; Hashemi, Mehrdad; Aghasadeghi, Mohammad Reza; Sadat, Seyed Mehdi

    2014-01-01

    Nanocarriers with various compositions and biological properties have been extensively applied for in vitro/in vivo drug and gene delivery. The family of nanocarriers includes polymeric nanoparticles, lipid-based carriers (liposomes/micelles), dendrimers, carbon nanotubes, and gold nanoparticles (nanoshells/nanocages). Among different delivery systems, polymeric carriers have several properties such as: easy to synthesize, inexpensive, biocompatible, biodegradable, non-immunogenic, non-toxic, and water soluble. In addition, cationic polymers seem to produce more stable complexes led to a more protection during cellular trafficking than cationic lipids. Nanoparticles often show significant adjuvant effects in vaccine delivery since they may be easily taken up by antigen presenting cells (APCs). Natural polymers such as polysaccharides and synthetic polymers have demonstrated great potential to form vaccine nanoparticles. The development of new adjuvants or delivery systems for DNA and protein immunization is an expanding research field. This review describes polymeric carriers especially PLGA, chitosan, and PEI as vaccine delivery systems.

  20. A double-blind trial of a new inactivated, trivalent, intra-nasal anti-influenza vaccine in general practice: relationship between immunogenicity and respiratory morbidity over the winter of 1997-98.

    PubMed

    Kiderman, A; Furst, A; Stewart, B; Greenbaum, E; Morag, A; Zakay-Rones, Z

    2001-02-01

    Influenza is responsible for considerable morbidity not only among older people but in younger age groups as well. However, most large-scale anti-influenza vaccination campaigns are still aimed principally at the elderly using injectable vaccines. Until now there has been much less emphasis on targeting younger populations or using intra-nasal vaccines in mass anti-influenza immunisation programmes. To assess the immunogenicity of a new inactivated intra-nasal anti-influenza vaccine and to measure its effect on respiratory morbidity in a volunteer general practice population. A prospective, double-blind, placebo-controlled trial using the new vaccine was carried out over the winter of 1997-98 on 274 healthy patients aged 12-60 from three Israeli general practices, 182 in the vaccine group and 92 in the placebo group. Following vaccination the changes in the antigen levels and episodes of respiratory illness in the vaccine and placebo groups were measured. Protective antibody levels occurred after a single dose of vaccine [influenza H1N1, 41% immune pre-vaccination to 73% post-vaccination; influenza H3N2, 35-66%; influenza B, 27-64%]. Between January and March 1998, when influenza activity was at a peak in Israel, the average number of respiratory illness events in the vaccine group [14 events/100 subjects per month] was significantly less than in the placebo group [22 events/100 subjects per month]; similarly, the average number of respiratory illness days in the vaccine group over the same period [69 days/100 subjects per month] was significantly less than in the placebo group [117 days/100 subjects per month]. The new vaccine possessed significant immunogenicity and was associated with a significant reduction in respiratory morbidity among a group of healthy older children and adults. Since intra-nasal vaccines are simpler to administer and more acceptable to the public than injections the vaccine's potential for use in routine anti-influenza vaccination

  1. Delivery cost analysis of a reactive mass cholera vaccination campaign: a case study of Shanchol™ vaccine use in Lake Chilwa, Malawi.

    PubMed

    Ilboudo, Patrick G; Le Gargasson, Jean-Bernard

    2017-12-19

    Cholera is a diarrheal disease that produces rapid dehydration. The infection is a significant cause of mortality and morbidity. Oral cholera vaccine (OCV) has been propagated for the prevention of cholera. Evidence on OCV delivery cost is insufficient in the African context. This study aims to analyze Shanchol vaccine delivery costs, focusing on the vaccination campaign in response of a cholera outbreak in Lake Chilwa, Malawi. The vaccination campaign was implemented in two rounds in February and March 2016. Structured questionnaires were used to collect costs incurred for each vaccination related activity, including vaccine procurement and shipment, training, microplanning, sensitization, social mobilization and vaccination rounds. Costs collected, including financial and economic costs were analyzed using Choltool, a standardized cholera cost calculator. In total, 67,240 persons received two complete doses of the vaccine. Vaccine coverage was higher in the first round than in the second. The two-dose coverage measured with the immunization card was estimated at 58%. The total financial cost incurred in implementing the campaign was US$480275 while the economic cost was US$588637. The total financial and economic costs per fully vaccinated person were US$7.14 and US$8.75, respectively, with delivery costs amounting to US$1.94 and US$3.55, respectively. Vaccine procurement and shipment accounted respectively for 73% and 59% of total financial and economic costs of the total vaccination campaign costs while the incurred personnel cost accounted for 13% and 29% of total financial and economic costs. Cost for delivering a single dose of Shanchol was estimated at US$0.97. This study provides new evidence on economic and financial costs of a reactive campaign implemented by international partners in collaboration with MoH. It shows that involvement of international partners' personnel may represent a substantial share of campaign's costs, affecting unit and vaccine

  2. Mucosal vaccines: a paradigm shift in the development of mucosal adjuvants and delivery vehicles.

    PubMed

    Srivastava, Atul; Gowda, Devegowda Vishakante; Madhunapantula, SubbaRao V; Shinde, Chetan G; Iyer, Meenakshi

    2015-04-01

    Mucosal immune responses are the first-line defensive mechanisms against a variety of infections. Therefore, immunizations of mucosal surfaces from which majority of infectious agents make their entry, helps to protect the body against infections. Hence, vaccinization of mucosal surfaces by using mucosal vaccines provides the basis for generating protective immunity both in the mucosal and systemic immune compartments. Mucosal vaccines offer several advantages over parenteral immunization. For example, (i) ease of administration; (ii) non-invasiveness; (iii) high-patient compliance; and (iv) suitability for mass vaccination. Despite these benefits, to date, only very few mucosal vaccines have been developed using whole microorganisms and approved for use in humans. This is due to various challenges associated with the development of an effective mucosal vaccine that can work against a variety of infections, and various problems concerned with the safe delivery of developed vaccine. For instance, protein antigen alone is not just sufficient enough for the optimal delivery of antigen(s) mucosally. Hence, efforts have been made to develop better prophylactic and therapeutic vaccines for improved mucosal Th1 and Th2 immune responses using an efficient and safe immunostimulatory molecule and novel delivery carriers. Therefore, in this review, we have made an attempt to cover the recent advancements in the development of adjuvants and delivery carriers for safe and effective mucosal vaccine production. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  3. Development of replication-competent viral vectors for HIV vaccine delivery

    PubMed Central

    Parks, Christopher L.; Picker, Louis J.; King, C. Richter

    2014-01-01

    Purpose of review Briefly describe some of the replication-competent (RC) vectors being investigated for development of candidate HIV vaccines focusing primarily on technologies that have advanced to testing in macaques or have entered clinical trials. Recent findings RC viral vectors have advanced to the stage were decisions can be made regarding future development of HIV vaccines. The viruses being used as RC vector platforms vary considerably, and their unique attributes make it possible to test multiple vaccine design concepts and also mimic various aspects of an HIV infection. RC viral vectors encoding SIV or HIV proteins can be used to safely immunize macaques, and in some cases, there is evidence of significant vaccine efficacy in challenge protection studies. Several live HIV vaccine vectors are in clinical trials to evaluate immunogenicity, safety, the effect of mucosal delivery, and potential effects of pre-existing immunity. Summary A variety of DNA and RNA viruses are being used to develop RC viral vectors for HIV vaccine delivery. Multiple viral vector platforms have proven to be safe and immunogenic with evidence of efficacy in macaques. Some of the more advanced HIV vaccine prototypes based on vesicular stomatitis virus, vaccinia virus, measles virus, and Sendai virus are in clinical trials. PMID:23925000

  4. Seasonal influenza vaccination delivery through community pharmacists in England: evaluation of the London pilot.

    PubMed

    Atkins, Katherine; van Hoek, Albert Jan; Watson, Conall; Baguelin, Marc; Choga, Lethiwe; Patel, Anika; Raj, Thara; Jit, Mark; Griffiths, Ulla

    2016-02-16

    To evaluate the effectiveness and cost of the pan-London pharmacy initiative, a programme that allows administration of seasonal influenza vaccination to eligible patients at pharmacies. We analysed 2013-2015 data on vaccination uptake in pharmacies via the Sonar reporting system, and the total vaccination uptake via 2011-2015 ImmForm general practitioner (GP) reporting system data. We conducted an online survey of London pharmacists who participate in the programme to assess time use data, vaccine choice, investment costs and opinions about the programme. We conducted an online survey of London GPs to assess vaccine choice of vaccine and opinions about the pharmacy vaccine delivery programme. All London boroughs. London-based GPs, and pharmacies that currently offer seasonal flu vaccination. Not applicable. Comparison of annual vaccine uptake in London across risk groups from years before pharmacy vaccination introduction to after pharmacy vaccination introduction. Completeness of vaccine uptake reporting data. Cost to the National Health Service (NHS) of flu vaccine delivery at pharmacies with that at GPs. Cost to pharmacists of flu delivery. Opinions of pharmacists and GPs regarding the flu vaccine pharmacy initiative. No significant change in the uptake of seasonal vaccination in any of the risk groups as a result of the pharmacy initiative. While on average a pharmacy-administered flu vaccine dose costs the NHS up to £2.35 less than a dose administered at a GP, a comparison of the 2 recording systems suggests there is substantial loss of data. Flu vaccine delivery through pharmacies shows potential for improving convenience for vaccine recipients. However, there is no evidence that vaccination uptake increases and the use of 2 separate recording systems leads to time-consuming data entry and missing vaccine record data. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. pH-Responsive Nanoparticle Vaccines for Dual-Delivery of Antigens and Immunostimulatory Oligonucleotides

    PubMed Central

    Wilson, John T.; Keller, Salka; Manganiello, Matthew J.; Cheng, Connie; Lee, Chen-Chang; Opara, Chinonso; Convertine, Anthony; Stayton, Patrick S.

    2013-01-01

    Protein subunit vaccines offer important potential advantages over live vaccine vectors, but generally elicit weaker and shorter-lived cellular immune responses. Here we investigate the use of pH-responsive, endosomolytic polymer nanoparticles that were originally developed for RNA delivery as vaccine delivery vehicles for enhancing cellular and humoral immune responses. Micellar nanoparticles were assembled from amphiphilic diblock copolymers composed of an ampholytic core-forming block and a re-designed polycationic corona block doped with thiol-reactive pyridyl disulfide groups to enable dual-delivery of antigens and immunostimulatory CpG oligodeoxynucleotide (CpG ODN) adjuvants. Polymers assembled into 23 nm particles with simultaneous packaging of CpG ODN and a thiolated protein antigen, ovalbumin (ova). Conjugation of ova to nanoparticles significantly enhanced antigen cross-presentation in vitro relative to free ova or an unconjugated, physical mixture of the parent compounds. Subcutaneous vaccination of mice with ova-nanoparticle conjugates elicited a significantly higher CD8+ T cell response (0.5% IFN-ɣ+ of CD8+) compared to mice vaccinated with free ova or a physical mixture of the two components. Significantly, immunization with ova-nanoparticle conjugates electrostatically complexed with CpG ODN (dual-delivery) enhanced CD8+ T cell responses (3.4% IFN-ɣ+ of CD8+) 7-, 18-, and 8-fold relative to immunization with conjugates, ova administered with free CpG, or a formulation containing free ova and CpG complexed to micelles, respectively. Similarly, dual-delivery carriers significantly increased CD4+IFN-ɣ+ (Th1) responses, and elicited a balanced IgG1/IgG2c antibody response. Intradermal administration further augmented cellular immune responses, with dual-delivery carriers inducing ~7% antigen-specific CD8+ T cells. This work demonstrates the ability of pH-responsive, endosomolytic nanoparticles to actively promote antigen cross-presentation and

  6. An Overview of Vaccination Strategies and Antigen Delivery Systems for Streptococcus agalactiae Vaccines in Nile Tilapia (Oreochromis niloticus).

    PubMed

    Munang'andu, Hetron Mweemba; Paul, Joydeb; Evensen, Øystein

    2016-12-13

    Streptococcus agalactiae is an emerging infectious disease adversely affecting Nile tilapia ( Niloticus oreochromis ) production in aquaculture. Research carried out in the last decade has focused on developing protective vaccines using different strategies, although no review has been carried out to evaluate the efficacy of these strategies. The purpose of this review is to provide a synopsis of vaccination strategies and antigen delivery systems currently used for S. agalactiae vaccines in tilapia. Furthermore, as shown herein, current vaccine designs include the use of replicative antigen delivery systems, such as attenuated virulent strains, heterologous vectors and DNA vaccines, while non-replicative vaccines include the inactivated whole cell (IWC) and subunit vaccines encoding different S. agalactiae immunogenic proteins. Intraperitoneal vaccination is the most widely used immunization strategy, although immersion, spray and oral vaccines have also been tried with variable success. Vaccine efficacy is mostly evaluated by use of the intraperitoneal challenge model aimed at evaluating the relative percent survival (RPS) of vaccinated fish. The major limitation with this approach is that it lacks the ability to elucidate the mechanism of vaccine protection at portals of bacterial entry in mucosal organs and prevention of pathology in target organs. Despite this, indications are that the correlates of vaccine protection can be established based on antibody responses and antigen dose, although these parameters require optimization before they can become an integral part of routine vaccine production. Nevertheless, this review shows that different approaches can be used to produce protective vaccines against S. agalactiae in tilapia although there is a need to optimize the measures of vaccine efficacy.

  7. An Overview of Vaccination Strategies and Antigen Delivery Systems for Streptococcus agalactiae Vaccines in Nile Tilapia (Oreochromis niloticus)

    PubMed Central

    Munang’andu, Hetron Mweemba; Paul, Joydeb; Evensen, Øystein

    2016-01-01

    Streptococcus agalactiae is an emerging infectious disease adversely affecting Nile tilapia (Niloticus oreochromis) production in aquaculture. Research carried out in the last decade has focused on developing protective vaccines using different strategies, although no review has been carried out to evaluate the efficacy of these strategies. The purpose of this review is to provide a synopsis of vaccination strategies and antigen delivery systems currently used for S. agalactiae vaccines in tilapia. Furthermore, as shown herein, current vaccine designs include the use of replicative antigen delivery systems, such as attenuated virulent strains, heterologous vectors and DNA vaccines, while non-replicative vaccines include the inactivated whole cell (IWC) and subunit vaccines encoding different S. agalactiae immunogenic proteins. Intraperitoneal vaccination is the most widely used immunization strategy, although immersion, spray and oral vaccines have also been tried with variable success. Vaccine efficacy is mostly evaluated by use of the intraperitoneal challenge model aimed at evaluating the relative percent survival (RPS) of vaccinated fish. The major limitation with this approach is that it lacks the ability to elucidate the mechanism of vaccine protection at portals of bacterial entry in mucosal organs and prevention of pathology in target organs. Despite this, indications are that the correlates of vaccine protection can be established based on antibody responses and antigen dose, although these parameters require optimization before they can become an integral part of routine vaccine production. Nevertheless, this review shows that different approaches can be used to produce protective vaccines against S. agalactiae in tilapia although there is a need to optimize the measures of vaccine efficacy. PMID:27983591

  8. Oral Cholera Vaccination Delivery Cost in Low- and Middle-Income Countries: An Analysis Based on Systematic Review.

    PubMed

    Mogasale, Vittal; Ramani, Enusa; Wee, Hyeseung; Kim, Jerome H

    2016-12-01

    Use of the oral cholera vaccine (OCV) is a vital short-term strategy to control cholera in endemic areas with poor water and sanitation infrastructure. Identifying, estimating, and categorizing the delivery costs of OCV campaigns are useful in analyzing cost-effectiveness, understanding vaccine affordability, and in planning and decision making by program managers and policy makers. To review and re-estimate oral cholera vaccination program costs and propose a new standardized categorization that can help in collation, analysis, and comparison of delivery costs across countries. Peer reviewed publications listed in PubMed database, Google Scholar and World Health Organization (WHO) websites and unpublished data from organizations involved in oral cholera vaccination. The publications and reports containing oral cholera vaccination delivery costs, conducted in low- and middle-income countries based on World Bank Classification. Limits are humans and publication date before December 31st, 2014. No participants are involved, only costs are collected. Oral cholera vaccination and cost estimation. A systematic review was conducted using pre-defined inclusion and exclusion criteria. Cost items were categorized into four main cost groups: vaccination program preparation, vaccine administration, adverse events following immunization and vaccine procurement; the first three groups constituting the vaccine delivery costs. The costs were re-estimated in 2014 US dollars (US$) and in international dollar (I$). Ten studies were identified and included in the analysis. The vaccine delivery costs ranged from US$0.36 to US$ 6.32 (in US$2014) which was equivalent to I$ 0.99 to I$ 16.81 (in I$2014). The vaccine procurement costs ranged from US$ 0.29 to US$ 29.70 (in US$2014), which was equivalent to I$ 0.72 to I$ 78.96 (in I$2014). The delivery costs in routine immunization systems were lowest from US$ 0.36 (in US$2014) equivalent to I$ 0.99 (in I$2014). The reported cost categories

  9. Experiences of operational costs of HPV vaccine delivery strategies in Gavi-supported demonstration projects

    PubMed Central

    Holroyd, Taylor; Nanda, Shreya; Bloem, Paul; Griffiths, Ulla K.; Sidibe, Anissa; Hutubessy, Raymond C. W.

    2017-01-01

    From 2012 to 2016, Gavi, the Vaccine Alliance, provided support for countries to conduct small-scale demonstration projects for the introduction of the human papillomavirus vaccine, with the aim of determining which human papillomavirus vaccine delivery strategies might be effective and sustainable upon national scale-up. This study reports on the operational costs and cost determinants of different vaccination delivery strategies within these projects across twelve countries using a standardized micro-costing tool. The World Health Organization Cervical Cancer Prevention and Control Costing Tool was used to collect costing data, which were then aggregated and analyzed to assess the costs and cost determinants of vaccination. Across the one-year demonstration projects, the average economic and financial costs per dose amounted to US$19.98 (standard deviation ±12.5) and US$8.74 (standard deviation ±5.8), respectively. The greatest activities representing the greatest share of financial costs were social mobilization at approximately 30% (range, 6–67%) and service delivery at about 25% (range, 3–46%). Districts implemented varying combinations of school-based, facility-based, or outreach delivery strategies and experienced wide variation in vaccine coverage, drop-out rates, and service delivery costs, including transportation costs and per diems. Size of target population, number of students per school, and average length of time to reach an outreach post influenced cost per dose. Although the operational costs from demonstration projects are much higher than those of other routine vaccine immunization programs, findings from our analysis suggest that HPV vaccination operational costs will decrease substantially for national introduction. Vaccination costs may be decreased further by annual vaccination, high initial investment in social mobilization, or introducing/strengthening school health programs. Our analysis shows that drivers of cost are dependent on

  10. Experiences of operational costs of HPV vaccine delivery strategies in Gavi-supported demonstration projects.

    PubMed

    Botwright, Siobhan; Holroyd, Taylor; Nanda, Shreya; Bloem, Paul; Griffiths, Ulla K; Sidibe, Anissa; Hutubessy, Raymond C W

    2017-01-01

    From 2012 to 2016, Gavi, the Vaccine Alliance, provided support for countries to conduct small-scale demonstration projects for the introduction of the human papillomavirus vaccine, with the aim of determining which human papillomavirus vaccine delivery strategies might be effective and sustainable upon national scale-up. This study reports on the operational costs and cost determinants of different vaccination delivery strategies within these projects across twelve countries using a standardized micro-costing tool. The World Health Organization Cervical Cancer Prevention and Control Costing Tool was used to collect costing data, which were then aggregated and analyzed to assess the costs and cost determinants of vaccination. Across the one-year demonstration projects, the average economic and financial costs per dose amounted to US$19.98 (standard deviation ±12.5) and US$8.74 (standard deviation ±5.8), respectively. The greatest activities representing the greatest share of financial costs were social mobilization at approximately 30% (range, 6-67%) and service delivery at about 25% (range, 3-46%). Districts implemented varying combinations of school-based, facility-based, or outreach delivery strategies and experienced wide variation in vaccine coverage, drop-out rates, and service delivery costs, including transportation costs and per diems. Size of target population, number of students per school, and average length of time to reach an outreach post influenced cost per dose. Although the operational costs from demonstration projects are much higher than those of other routine vaccine immunization programs, findings from our analysis suggest that HPV vaccination operational costs will decrease substantially for national introduction. Vaccination costs may be decreased further by annual vaccination, high initial investment in social mobilization, or introducing/strengthening school health programs. Our analysis shows that drivers of cost are dependent on

  11. Intranasal and sublingual delivery of inactivated polio vaccine.

    PubMed

    Kraan, Heleen; Soema, Peter; Amorij, Jean-Pierre; Kersten, Gideon

    2017-05-09

    Polio is on the brink of eradication. Improved inactivated polio vaccines (IPV) are needed towards complete eradication and for the use in the period thereafter. Vaccination via mucosal surfaces has important potential advantages over intramuscular injection using conventional needle and syringe, the currently used delivery method for IPV. One of them is the ability to induce both serum and mucosal immune responses: the latter may provide protection at the port of virus entry. The current study evaluated the possibilities of polio vaccination via mucosal surfaces using IPV based on attenuated Sabin strains. Mice received three immunizations with trivalent sIPV via intramuscular injection, or via the intranasal or sublingual route. The need of an adjuvant for the mucosal routes was investigated as well, by testing sIPV in combination with the mucosal adjuvant cholera toxin. Both intranasal and sublingual sIPV immunization induced systemic polio-specific serum IgG in mice that were functional as measured by poliovirus neutralization. Intranasal administration of sIPV plus adjuvant induced significant higher systemic poliovirus type 3 neutralizing antibody titers than sIPV delivered via the intramuscular route. Moreover, mucosal sIPV delivery elicited polio-specific IgA titers at different mucosal sites (IgA in saliva, fecal extracts and intestinal tissue) and IgA-producing B-cells in the spleen, where conventional intramuscular vaccination was unable to do so. However, it is likely that a mucosal adjuvant is required for sublingual vaccination. Further research on polio vaccination via sublingual mucosal route should include the search for safe and effective adjuvants, and the development of novel oral dosage forms that improve antigen uptake by oral mucosa, thereby increasing vaccine immunogenicity. This study indicates that both the intranasal and sublingual routes might be valuable approaches for use in routine vaccination or outbreak control in the period after

  12. Mesoporous silica nanoparticles as antigen carriers and adjuvants for vaccine delivery

    NASA Astrophysics Data System (ADS)

    Mody, Karishma T.; Popat, Amirali; Mahony, Donna; Cavallaro, Antonino S.; Yu, Chengzhong; Mitter, Neena

    2013-05-01

    Vaccines have been at the forefront of improving human health for over two centuries. The challenges faced in developing effective vaccines flow from complexities associated with the immune system and requirement of an efficient and safe adjuvant to induce a strong adaptive immune response. Development of an efficient vaccine formulation requires careful selection of a potent antigen, efficient adjuvant and route of delivery. Adjuvants are immunological agents that activate the antigen presenting cells (APCs) and elicit a strong immune response. In the past decade, the use of mesoporous silica nanoparticles (MSNs) has gained significant attention as potential delivery vehicles for various biomolecules. In this review, we aim to highlight the potential of MSNs as vaccine delivery vehicles and their ability to act as adjuvants. We have provided an overview on the latest progress on synthesis, adsorption and release kinetics and biocompatibility of MSNs as next generation antigen carriers and adjuvants. A comprehensive summary on the ability of MSNs to deliver antigens and elicit both humoral and cellular immune responses is provided. Finally, we give insight on fundamental challenges and some future prospects of these nanoparticles as adjuvants.

  13. Recent advancement of gelatin nanoparticles in drug and vaccine delivery.

    PubMed

    Sahoo, Nityananda; Sahoo, Ranjan Ku; Biswas, Nikhil; Guha, Arijit; Kuotsu, Ketousetuo

    2015-11-01

    Novel drug delivery system using nanoscale materials with a broad spectrum of applications provides a new therapeutic foundation for technological integration and innovation. Nanoparticles are suitable drug carrier for various routes of administration as well as rapid recognition by the immune system. Gelatin, the biological macromolecule is a versatile drug/vaccine delivery carrier in pharmaceutical field due to its biodegradable, biocompatible, non-antigenicity and low cost with easy availability. The surface of gelatin nanoparticles can be modified with site-specific ligands, cationized with amine derivatives or, coated with polyethyl glycols to achieve targeted and sustained release drug delivery. Compared to other colloidal carriers, gelatin nanoparticles are better stable in biological fluids to provide the desired controlled and sustained release of entrapped drug molecules. The current review highlights the different formulation aspects of gelatin nanoparticles which affect the particle characteristics like zeta potential, polydispersity index, entrapment efficacy and drug release properties. It has also given emphasis on the major applications of gelatin nanoparticles in drug and vaccine delivery, gene delivery to target tissues and nutraceutical delivery for improving the poor bioavailabity of bioactive phytonutrients. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Enhanced Delivery and Potency of Self-Amplifying mRNA Vaccines by Electroporation in Situ

    PubMed Central

    Cu, Yen; Broderick, Kate E.; Banerjee, Kaustuv; Hickman, Julie; Otten, Gillis; Barnett, Susan; Kichaev, Gleb; Sardesai, Niranjan Y.; Ulmer, Jeffrey B.; Geall, Andrew

    2013-01-01

    Nucleic acid-based vaccines such as viral vectors, plasmid DNA (pDNA), and mRNA are being developed as a means to address limitations of both live-attenuated and subunit vaccines. DNA vaccines have been shown to be potent in a wide variety of animal species and several products are now licensed for commercial veterinary but not human use. Electroporation delivery technologies have been shown to improve the generation of T and B cell responses from synthetic DNA vaccines in many animal species and now in humans. However, parallel RNA approaches have lagged due to potential issues of potency and production. Many of the obstacles to mRNA vaccine development have recently been addressed, resulting in a revival in the use of non-amplifying and self-amplifying mRNA for vaccine and gene therapy applications. In this paper, we explore the utility of EP for the in vivo delivery of large, self-amplifying mRNA, as measured by reporter gene expression and immunogenicity of genes encoding HIV envelope protein. These studies demonstrated that EP delivery of self-amplifying mRNA elicited strong and broad immune responses in mice, which were comparable to those induced by EP delivery of pDNA. PMID:26344119

  15. Oral Cholera Vaccination Delivery Cost in Low- and Middle-Income Countries: An Analysis Based on Systematic Review

    PubMed Central

    Ramani, Enusa; Wee, Hyeseung; Kim, Jerome H.

    2016-01-01

    Background Use of the oral cholera vaccine (OCV) is a vital short-term strategy to control cholera in endemic areas with poor water and sanitation infrastructure. Identifying, estimating, and categorizing the delivery costs of OCV campaigns are useful in analyzing cost-effectiveness, understanding vaccine affordability, and in planning and decision making by program managers and policy makers. Objectives To review and re-estimate oral cholera vaccination program costs and propose a new standardized categorization that can help in collation, analysis, and comparison of delivery costs across countries. Data sources Peer reviewed publications listed in PubMed database, Google Scholar and World Health Organization (WHO) websites and unpublished data from organizations involved in oral cholera vaccination. Study eligibility criteria The publications and reports containing oral cholera vaccination delivery costs, conducted in low- and middle-income countries based on World Bank Classification. Limits are humans and publication date before December 31st, 2014. Participants No participants are involved, only costs are collected. Intervention Oral cholera vaccination and cost estimation. Study appraisal and synthesis method A systematic review was conducted using pre-defined inclusion and exclusion criteria. Cost items were categorized into four main cost groups: vaccination program preparation, vaccine administration, adverse events following immunization and vaccine procurement; the first three groups constituting the vaccine delivery costs. The costs were re-estimated in 2014 US dollars (US$) and in international dollar (I$). Results Ten studies were identified and included in the analysis. The vaccine delivery costs ranged from US$0.36 to US$ 6.32 (in US$2014) which was equivalent to I$ 0.99 to I$ 16.81 (in I$2014). The vaccine procurement costs ranged from US$ 0.29 to US$ 29.70 (in US$2014), which was equivalent to I$ 0.72 to I$ 78.96 (in I$2014). The delivery costs in

  16. Multifunctional particle-constituted microneedle arrays as cutaneous or mucosal vaccine adjuvant-delivery systems

    PubMed Central

    Wang, Xueting; Wang, Ning; Li, Ning; Zhen, Yuanyuan; Wang, Ting

    2016-01-01

    ABSTRACT To overcome drawbacks of current injection vaccines, such as causing needle phobia, needing health professionals for inoculation, and generating dangerous sharps wastes, researchers have designed novel vaccines that are combined with various microneedle arrays (MAs), in particular, with the multifunctional particle-constructed MAs (MPMAs). MPMAs prove able to enhance vaccine stability through incorporating vaccine ingredients in the carrier, and can be painlessly inoculated by minimally trained workers or by self-administration, leaving behind no metal needle pollution while eliciting robust systemic and mucosal immunity to antigens, thanks to delivering vaccines to cutaneous or mucosal compartments enriched in professional antigen-presenting cells (APCs). Especially, MPMAs can be easily integrated with functional molecules fulfilling targeting vaccine delivery or controlling immune response toward a Th1 or Th2 pathway to generate desired immunity against pathogens. Herein, we introduce the latest research and development of various MPMAs which are a novel but promising vaccine adjuvant delivery system (VADS). PMID:27159879

  17. Induction of mucosal immune responses and protection of cattle against direct-contact challenge by intranasal delivery with foot-and-mouth disease virus antigen mediated by nanoparticles

    PubMed Central

    Pan, Li; Zhang, Zhongwang; Lv, Jianliang; Zhou, Peng; Hu, Wenfa; Fang, Yuzhen; Chen, Haotai; Liu, Xinsheng; Shao, Junjun; Zhao, Furong; Ding, Yaozhong; Lin, Tong; Chang, Huiyun; Zhang, Jie; Zhang, Yongguang; Wang, Yonglu

    2014-01-01

    The aim of this study was to enhance specific mucosal, systemic, and cell-mediated immunity and to induce earlier onset of protection against direct-contact challenge in cattle by intranasal delivery of a nanoparticle-based nasal vaccine against type A foot-and-mouth disease (FMD). In this study, two kinds of nanoparticle-based nasal vaccines against type A FMD were designed: (1) chitosan-coated poly(lactic-co-glycolic acid) (PLGA) loaded with plasmid DNA (Chi-PLGA-DNA) and (2) chitosan-trehalose and inactivated foot-and-mouth disease virus (FMDV) (Chi-Tre-Inactivated). Cattle were immunized by an intranasal route with nanoparticles and then challenged for 48 hours by direct contact with two infected donor cattle per pen. Donors were inoculated intradermally in the tongue 48 hours before challenge, with 0.2 mL cattle-passaged FMDV. Serological and mucosal antibody responses were evaluated, and virus excretion and the number of contact infections were quantified. FMDV-specific secretory immunoglobulin (Ig)A (sIgA) antibodies in nasal washes were initially detected at 4 days postvaccination (dpv) with two kinds of nanoparticles. The highest levels of sIgA expression were observed in nasal washes, at 10 dpv, from animals with Chi-PLGA-DNA nanoparticles, followed by animals immunized once by intranasal route with a double dose of Chi-Tre-Inactivated nanoparticles and animals immunized by intranasal route three times with Chi-Tre-Inactivated nanoparticles (P<0.05). FMDV-specific IgA antibodies in serum showed a similar pattern. All animals immunized by intranasal route developed low levels of detectable IgG in serum at 10 dpv. Following stimulation with FMDV, the highest levels of proliferation were observed in splenocytes harvested from Chi-PLGA-DNA-immunized animals, followed by proliferation of cells harvested from Chi-Tre-Inactivated nanoparticle-immunized animals (P<0.05). Higher protection rates were associated with the highest sIgA antibody responses induced in

  18. Targeted delivery of antigen to hamster nasal lymphoid tissue with M-cell-directed lectins.

    PubMed Central

    Giannasca, P J; Boden, J A; Monath, T P

    1997-01-01

    The nasal cavity of a rodent is lined by an epithelium organized into distinct regional domains responsible for specific physiological functions. Aggregates of nasal lymphoid tissue (NALT) located at the base of the nasal cavity are believed to be sites of induction of mucosal immune responses to airborne antigens. The epithelium overlying NALT contains M cells which are specialized for the transcytosis of immunogens, as demonstrated in other mucosal tissues. We hypothesized that NALT M cells are characterized by distinct glycoconjugate receptors which influence antigen uptake and immune responses to transcytosed antigens. To identify glycoconjugates that may distinguish NALT M cells from other cells of the respiratory epithelium (RE), we performed lectin histochemistry on sections of the hamster nasal cavity with a panel of lectins. Many classes of glycoconjugates were found on epithelial cells in this region. While most lectins bound to sites on both the RE and M cells, probes capable of recognizing alpha-linked galactose were found to label the follicle-associated epithelium (FAE) almost exclusively. By morphological criteria, the FAE contains >90% M cells. To determine if apical glycoconjugates on M cells were accessible from the nasal cavity, an M-cell-selective lectin and a control lectin in parallel were administered intranasally to hamsters. The M-cell-selective lectin was found to specifically target the FAE, while the control lectin did not. Lectin bound to M cells in vivo was efficiently endocytosed, consistent with the role of M cells in antigen transport. Intranasal immunization with lectin-test antigen conjugates without adjuvant stimulated induction of specific serum immunoglobulin G, whereas antigen alone or admixed with lectin did not. The selective recognition of NALT M cells by a lectin in vivo provides a model for microbial adhesin-host cell receptor interactions on M cells and the targeted delivery of immunogens to NALT following intranasal

  19. Paracellular permeation-enhancing effect of AT1002 C-terminal amidation in nasal delivery

    PubMed Central

    Song, Keon-Hyoung; Kim, Sang-Bum; Shim, Chang-Koo; Chung, Suk-Jae; Kim, Dae-Duk; Rhee, Sang-Ki; Choi, Guang J; Kim, Chul-Hyun; Kim, Kiyoung

    2015-01-01

    Background The identification of permeation enhancers has gained interest in the development of drug delivery systems. A six-mer peptide, H-FCIGRL-OH (AT1002), is a tight junction modulator with promising permeation-enhancing activity. AT1002 enhances the transport of molecular weight markers or agents with low bioavailability with no cytotoxicity. However, AT1002 is not stable in neutral pH or after incubation under physiological conditions, which is necessary to fully uncover its permeation-enhancing effect. Thus, we increased the stability or mitigated the instability of AT1002 by modifying its terminal amino acids and evaluated its subsequent biological activity. Methods C-terminal-amidated (FCIGRL-NH2, Pep1) and N-terminal-acetylated (Ac-FCIGRL, Pep2) peptides were analyzed by liquid chromatography–mass spectrometry. We further assessed cytotoxicity on cell monolayers, as well as the permeation-enhancing activity following nasal administration of the paracellular marker mannitol. Results Pep1 was nontoxic to cell monolayers and showed a relatively low decrease in peak area compared to AT1002. In addition, administration of mannitol with Pep1 resulted in significant increases in the area under the plasma concentration–time curve and peak plasma concentration at 3.63-fold and 2.68-fold, respectively, compared to mannitol alone. In contrast, no increase in mannitol concentration was shown with mannitol/AT1002 or mannitol/Pep2 compared to the control. Thus, Pep1 increased the stability or possibly reduced the instability of AT1002, which resulted in an increased permeation-enhancing effect of AT1002. Conclusion These results suggest the potential usefulness of C-terminal-amidated AT1002 in enhancing nasal drug delivery, which may lead to the development of a practical drug delivery technology for drugs with low bioavailability. PMID:25848218

  20. Mucosal vaccination--an old but still vital strategy.

    PubMed

    Długońska, Henryka; Grzybowski, Marcin

    2012-01-01

    The basic premise of vaccinology is to achieve strong protective immunity against defined infectious agents by a vaccine mimicking the effects of natural primary exposure to a pathogen. Because an exposure of humans and animals to microbes occurs mostly through mucosal surfaces, targeting the mucosa seems a rational and efficient vaccination strategy. Many experimental and clinical data confirmed that mucosal immunization offers many advantages over widely used in human and veterinary medicine subcutaneous or intramuscular immunization. In the present article selected aspects regarding mucosal vaccination are discussed. The structure and function of mucosa-associated lymphoid tissue (MALT), comprised of four main mucosal compartments forming a structural and functional unity as well as pivotal cellular MALT components (dendritic and M cells) were briefly characterized. Particular attention was focused on the mode of simple but efficacious delivery of vaccine antigens to mucosal surfaces. A few trials to generate potential mucosal vaccines against toxoplasmosis introduced by nasal or oral routes to experimental animals are also presented.

  1. PLGA particulate delivery systems for subunit vaccines: Linking particle properties to immunogenicity.

    PubMed

    Silva, A L; Soema, P C; Slütter, B; Ossendorp, F; Jiskoot, W

    2016-04-02

    Among the emerging subunit vaccines are recombinant protein- and synthetic peptide-based vaccine formulations. However, proteins and peptides have a low intrinsic immunogenicity. A common strategy to overcome this is to co-deliver (an) antigen(s) with (an) immune modulator(s) by co-encapsulating them in a particulate delivery system, such as poly(lactic-co-glycolic acid) (PLGA) particles. Particulate PLGA formulations offer many advantages for antigen delivery as they are biocompatible and biodegradable; can protect the antigens from degradation and clearance; allow for co-encapsulation of antigens and immune modulators; can be targeted to antigen presenting cells; and their particulate nature can increase uptake and cross-presentation by mimicking the size and shape of an invading pathogen. In this review we discuss the pros and cons of using PLGA particulate formulations for subunit vaccine delivery and provide an overview of formulation parameters that influence their adjuvanticity and the ensuing immune response.

  2. Production of recombinant subunit vaccines: protein immunogens, live delivery systems and nucleic acid vaccines.

    PubMed

    Liljeqvist, S; Ståhl, S

    1999-07-30

    The first scientific attempts to control an infectious disease can be attributed to Edward Jenner, who, in 1796 inoculated an 8-year-old boy with cowpox (vaccinia), giving the boy protection against subsequent challenge with virulent smallpox. Thanks to the successful development of vaccines, many major diseases, such as diphtheria, poliomyelitis and measles, are nowadays kept under control, and in the case of smallpox, the dream of eradication has been fulfilled. Yet, there is a growing need for improvements of existing vaccines in terms of increased efficacy and improved safety, besides the development of completely new vaccines. Better technological possibilities, combined with increased knowledge in related fields, such as immunology and molecular biology, allow for new vaccination strategies. Besides the classical whole-cell vaccines, consisting of killed or attenuated pathogens, new vaccines based on the subunit principle, have been developed, e.g. the Hepatitis B surface protein vaccine and the Haemophilus influenzae type b vaccine. Recombinant techniques are now dominating in the strive for an ideal vaccine, being safe and cheap, heat-stable and easy to administer, preferably single-dose, and capable of inducing broad immune response with life-long memory both in adults and in infants. This review will describe different recombinant approaches used in the development of novel subunit vaccines, including design and production of protein immunogens, the development of live delivery systems and the state-of-the-art for nucleic acids vaccines.

  3. Peptide/protein vaccine delivery system based on PLGA particles.

    PubMed

    Allahyari, Mojgan; Mohit, Elham

    2016-03-03

    Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DC-based vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to M-cells will be highlighted.

  4. Peptide/protein vaccine delivery system based on PLGA particles

    PubMed Central

    Allahyari, Mojgan; Mohit, Elham

    2016-01-01

    abstract Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DC-based vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to M-cells will be highlighted. PMID:26513024

  5. Impact of airborne particle size, acoustic airflow and breathing pattern on delivery of nebulized antibiotic into the maxillary sinuses using a realistic human nasal replica.

    PubMed

    Leclerc, Lara; Pourchez, Jérémie; Aubert, Gérald; Leguellec, Sandrine; Vecellio, Laurent; Cottier, Michèle; Durand, Marc

    2014-09-01

    Improvement of clinical outcome in patients with sinuses disorders involves targeting delivery of nebulized drug into the maxillary sinuses. We investigated the impact of nebulization conditions (with and without 100 Hz acoustic airflow), particle size (9.9 μm, 2.8 μm, 550 nm and 230 nm) and breathing pattern (nasal vs. no nasal breathing) on enhancement of aerosol delivery into the sinuses using a realistic nasal replica developed by our team. After segmentation of the airways by means of high-resolution computed tomography scans, a well-characterized nasal replica was created using a rapid prototyping technology. A total of 168 intrasinus aerosol depositions were performed with changes of aerosol particle size and breathing patterns under different nebulization conditions using gentamicin as a marker. The results demonstrate that the fraction of aerosol deposited in the maxillary sinuses is enhanced by use of submicrometric aerosols, e.g. 8.155 ± 1.476 mg/L of gentamicin in the left maxillary sinus for the 2.8 μm particles vs. 2.056 ± 0.0474 for the 550 nm particles. Utilization of 100-Hz acoustic airflow nebulization also produced a 2- to 3-fold increase in drug deposition in the maxillary sinuses (e.g. 8.155 ± 1.476 vs. 3.990 ± 1.690 for the 2.8 μm particles). Our study clearly shows that optimum deposition was achieved using submicrometric particles and 100-Hz acoustic airflow nebulization with no nasal breathing. It is hoped that our new respiratory nasal replica will greatly facilitate the development of more effective delivery systems in the future.

  6. Transfollicular delivery takes root: the future for vaccine design?

    PubMed

    Hansen, Steffi; Lehr, Claus-Michael

    2014-01-01

    The immunological environment of hair follicles has lately received the attention of researchers in the context of transfollicular drug delivery, particularly for improving needle-free transcutaneous immunization. Hair follicles represent shunt pathways across the stratum corneum barrier, which may facilitate the absorption of large or hydrophilic molecules such as vaccine antigens. Currently researchers have identified opportunities and challenges created by transfollicular vaccination. Nanotechnology may facilitate transfollicular delivery in several ways as nanoparticles penetrate deeper and to a higher extent into hair follicles than solutions. Also, nanoencapsulation can stabilize antigens and increase their antigenicity. This seems necessary as only a limited portion of topically applied antigen is available via the hair follicles and as the responsiveness of perifollicular Langerhans cells varies during hair cycle. These problems may be overcome by developing more efficient adjuvant-coupled nanocarriers with high antigen payload.

  7. Vial usage, device dead space, vaccine wastage, and dose accuracy of intradermal delivery devices for inactivated poliovirus vaccine (IPV).

    PubMed

    Jarrahian, Courtney; Rein-Weston, Annie; Saxon, Gene; Creelman, Ben; Kachmarik, Greg; Anand, Abhijeet; Zehrung, Darin

    2017-03-27

    Intradermal delivery of a fractional dose of inactivated poliovirus vaccine (IPV) offers potential benefits compared to intramuscular (IM) delivery, including possible cost reductions and easing of IPV supply shortages. Objectives of this study were to assess intradermal delivery devices for dead space, wastage generated by the filling process, dose accuracy, and total number of doses that can be delivered per vial. Devices tested included syringes with staked (fixed) needles (autodisable syringes and syringes used with intradermal adapters), a luer-slip needle and syringe, a mini-needle syringe, a hollow microneedle device, and disposable-syringe jet injectors with their associated filling adapters. Each device was used to withdraw 0.1-mL fractional doses from single-dose IM glass vials which were then ejected into a beaker. Both vial and device were weighed before and after filling and again after expulsion of liquid to record change in volume at each stage of the process. Data were used to calculate the number of doses that could potentially be obtained from multidose vials. Results show wide variability in dead space, dose accuracy, overall wastage, and total number of doses that can be obtained per vial among intradermal delivery devices. Syringes with staked needles had relatively low dead space and low overall wastage, and could achieve a greater number of doses per vial compared to syringes with a detachable luer-slip needle. Of the disposable-syringe jet injectors tested, one was comparable to syringes with staked needles. If intradermal delivery of IPV is introduced, selection of an intradermal delivery device can have a substantial impact on vaccine wasted during administration, and thus on the required quantity of vaccine that needs to be purchased. An ideal intradermal delivery device should be not only safe, reliable, accurate, and acceptable to users and vaccine recipients, but should also have low dead space, high dose accuracy, and low overall

  8. A Review of Intra- and Extracellular Antigen Delivery Systems for Virus Vaccines of Finfish

    PubMed Central

    Munang'andu, Hetron Mweemba; Evensen, Øystein

    2015-01-01

    Vaccine efficacy in aquaculture has for a long time depended on evaluating relative percent survival and antibody responses after vaccination. However, current advances in vaccine immunology show that the route in which antigens are delivered into cells is deterministic of the type of adaptive immune response evoked by vaccination. Antigens delivered by the intracellular route induce MHC-I restricted CD8+ responses while antigens presented through the extracellular route activate MHC-II restricted CD4+ responses implying that the route of antigen delivery is a conduit to induction of B- or T-cell immune responses. In finfish, different antigen delivery systems have been explored that include live, DNA, inactivated whole virus, fusion protein, virus-like particles, and subunit vaccines although mechanisms linking these delivery systems to protective immunity have not been studied in detail. Hence, in this review we provide a synopsis of different strategies used to administer viral antigens via the intra- or extracellular compartments. Further, we highlight the differences in immune responses induced by antigens processed by the endogenous route compared to exogenously processed antigens. Overall, we anticipate that the synopsis put together in this review will shed insights into limitations and successes of the current vaccination strategies used in finfish vaccinology. PMID:26065009

  9. Breath-powered sumatriptan dry nasal powder: an intranasal medication delivery system for acute treatment of migraine.

    PubMed

    Tepper, Stewart J; Johnstone, Merrilee R

    2018-01-01

    There is a need for fast-acting, non-oral medication options for migraine because some attacks develop rapidly and some are accompanied by nausea, vomiting, and gastroparesis, which can hinder oral medication uptake and absorption. The most commonly prescribed migraine medications are oral triptans, with sumatriptan as the most common. However, oral triptans are associated with adverse events (AEs) of atypical sensations that may be problematic for patients. Subcutaneous (SC) injectable sumatriptan and conventional liquid triptan nasal spray formulations are also available, but the frequency of atypical sensations is the highest with SC sumatriptan, and the intense bitter taste of conventional liquid triptan nasal spray discourages use. AVP-825 (ONZETRA ® Xsail ® ) is an intranasal medication delivery system containing 22 mg sumatriptan nasal powder that is now available in the USA for the acute treatment of migraine with or without aura in adults. The objective of this review is to summarize the development of AVP-825, which utilizes unique features of nasal anatomy to achieve efficient absorption and reduced systemic exposure. Literature searches for "sumatriptan nasal powder", "AVP-825", and "sumatriptan intranasal" were conducted. Review articles and pharmacokinetic, Phase II and Phase III studies were evaluated. AVP-825 demonstrates an earlier onset of efficacy and lower rate of atypical sensations than the oral standard of care, which can be attributed to its fast absorption and low systemic exposure. AEs of abnormal taste are predominantly mild. These results confirm the initial design concept for AVP-825, which aligned pharmacokinetics, anatomy, and drug presentation in a novel device to achieve optimal outcomes for the acute treatment of migraine.

  10. Turning self-destructing Salmonella into a universal DNA vaccine delivery platform.

    PubMed

    Kong, Wei; Brovold, Matthew; Koeneman, Brian A; Clark-Curtiss, Josephine; Curtiss, Roy

    2012-11-20

    We previously developed a biological containment system using recombinant Salmonella Typhimurium strains that are attenuated yet capable of synthesizing protective antigens. The regulated delayed attenuation and programmed self-destructing features designed into these S. Typhimurium strains enable them to efficiently colonize host tissues and allow release of the bacterial cell contents after lysis. To turn such a recombinant attenuated Salmonella vaccine (RASV) strain into a universal DNA vaccine-delivery vehicle, our approach was to genetically modify RASV strains to display a hyperinvasive phenotype to maximize Salmonella host entry and host cell internalization, to enable Salmonella endosomal escape to release a DNA vaccine into the cytosol, and to decrease Salmonella-induced pyroptosis/apoptosis that allows the DNA vaccine time to traffic to the nucleus for efficient synthesis of encoded protective antigens. A DNA vaccine vector that encodes a domain that contributes to the arabinose-regulated lysis phenotype but has a eukaryotic promoter was constructed. The vector was then improved by insertion of multiple DNA nuclear-targeting sequences for efficient nuclear trafficking and gene expression, and by increasing nuclease resistance to protect the plasmid from host degradation. A DNA vaccine encoding influenza WSN virus HA antigen delivered by the RASV strain with the best genetic attributes induced complete protection to mice against a lethal influenza virus challenge. Adoption of these technological improvements will revolutionize means for effective delivery of DNA vaccines to stimulate mucosal, systemic, and cellular protective immunities, and lead to a paradigm shift in cost-effective control and prevention of a diversity of diseases.

  11. Turning self-destructing Salmonella into a universal DNA vaccine delivery platform

    PubMed Central

    Kong, Wei; Brovold, Matthew; Koeneman, Brian A.; Clark-Curtiss, Josephine; Curtiss, Roy

    2012-01-01

    We previously developed a biological containment system using recombinant Salmonella Typhimurium strains that are attenuated yet capable of synthesizing protective antigens. The regulated delayed attenuation and programmed self-destructing features designed into these S. Typhimurium strains enable them to efficiently colonize host tissues and allow release of the bacterial cell contents after lysis. To turn such a recombinant attenuated Salmonella vaccine (RASV) strain into a universal DNA vaccine-delivery vehicle, our approach was to genetically modify RASV strains to display a hyperinvasive phenotype to maximize Salmonella host entry and host cell internalization, to enable Salmonella endosomal escape to release a DNA vaccine into the cytosol, and to decrease Salmonella-induced pyroptosis/apoptosis that allows the DNA vaccine time to traffic to the nucleus for efficient synthesis of encoded protective antigens. A DNA vaccine vector that encodes a domain that contributes to the arabinose-regulated lysis phenotype but has a eukaryotic promoter was constructed. The vector was then improved by insertion of multiple DNA nuclear-targeting sequences for efficient nuclear trafficking and gene expression, and by increasing nuclease resistance to protect the plasmid from host degradation. A DNA vaccine encoding influenza WSN virus HA antigen delivered by the RASV strain with the best genetic attributes induced complete protection to mice against a lethal influenza virus challenge. Adoption of these technological improvements will revolutionize means for effective delivery of DNA vaccines to stimulate mucosal, systemic, and cellular protective immunities, and lead to a paradigm shift in cost-effective control and prevention of a diversity of diseases. PMID:23129620

  12. Characterization of deposition from nasal spray devices using a computational fluid dynamics model of the human nasal passages.

    PubMed

    Kimbell, Julia S; Segal, Rebecca A; Asgharian, Bahman; Wong, Brian A; Schroeter, Jeffry D; Southall, Jeremy P; Dickens, Colin J; Brace, Geoff; Miller, Frederick J

    2007-01-01

    Many studies suggest limited effectiveness of spray devices for nasal drug delivery due primarily to high deposition and clearance at the front of the nose. Here, nasal spray behavior was studied using experimental measurements and a computational fluid dynamics model of the human nasal passages constructed from magnetic resonance imaging scans of a healthy adult male. Eighteen commercially available nasal sprays were analyzed for spray characteristics using laser diffraction, high-speed video, and high-speed spark photography. Steadystate, inspiratory airflow (15 L/min) and particle transport were simulated under measured spray conditions. Simulated deposition efficiency and spray behavior were consistent with previous experimental studies, two of which used nasal replica molds based on this nasal geometry. Deposition fractions (numbers of deposited particles divided by the number released) of 20- and 50-microm particles exceeded 90% in the anterior part of the nose for most simulated conditions. Predicted particle penetration past the nasal valve improved when (1) the smaller of two particle sizes or the lower of two spray velocities was used, (2) the simulated nozzle was positioned 1.0 rather than 0.5 or 1.5 cm into the nostril, and (3) inspiratory airflow was present rather than absent. Simulations also predicted that delaying the appearance of normal inspiratory airflow more than 1 sec after the release of particles produced results equivalent to cases in which no inspiratory airflow was present. These predictions contribute to more effective design of drug delivery devices through a better understanding of the effects of nasal airflow and spray characteristics on particle transport in the nose.

  13. Immunogenicity of Live Attenuated B. pertussis BPZE1 Producing the Universal Influenza Vaccine Candidate M2e

    PubMed Central

    Kammoun, Hana; Roux, Xavier; Raze, Dominique; Debrie, Anne-Sophie; De Filette, Marina; Ysenbaert, Tine; Mielcarek, Nathalie; Saelens, Xavier; Fiers, Walter; Locht, Camille

    2013-01-01

    Background Intranasal delivery of vaccines directed against respiratory pathogens is an attractive alternative to parenteral administration. However, using this delivery route for inactivated vaccines usually requires the use of potent mucosal adjuvants, and no such adjuvant has yet been approved for human use. Methodology/Principal Findings We have developed a live attenuated Bordetella pertussis vaccine, called BPZE1, and show here that it can be used to present the universal influenza virus epitope M2e to the mouse respiratory tract to prime for protective immunity against viral challenge. Three copies of M2e were genetically fused to the N-terminal domain of filamentous hemagglutinin (FHA) and produced in recombinant BPZE1 derivatives in the presence or absence of endogenous full-length FHA. Only in the absence of FHA intranasal administration of the recombinant BPZE1 derivative induced antibody responses to M2e and effectively primed BALB/c mice for protection against influenza virus-induced mortality and reduced the viral load after challenge. Strong M2e-specific antibody responses and protection were observed after a single nasal administration with the recombinant BPZE1 derivative, followed by a single administration of M2e linked to a virus-like particle without adjuvant, whereas priming alone with the vaccine strain did not protect. Conclusions/Significance Using recombinant FHA-3M2e-producing BPZE1 derivatives for priming and the universal influenza M2e peptide linked to virus-like particles for boosting may constitute a promising approach for needle-free and adjuvant-free nasal vaccination against influenza. PMID:23555631

  14. Trends affecting the future of vaccine development and delivery: The role of demographics, regulatory science, the anti-vaccine movement, and vaccinomics

    PubMed Central

    Poland, Gregory A.; Jacobson, Robert M.; Ovsyannikova, Inna G.

    2009-01-01

    Important scientific, cultural, temporal, and secular issues impact the development of, and delivery of vaccines. In this paper we discuss the impact of demographics, regulatory science, the anti-vaccine movement, and finally the impact of the new biology and individualized medicine, which we call vaccinomics, on vaccine development and delivery. A description of the issues and how they have, are, or should be impacting vaccinology is provided, and hopefully will result in increased attention and discussion among vaccinologists. These issues have been under-valued, under-discussed, and in some cases, ignored. We hope that discussion of these issues will result in changes in how we develop, and how we communicate those developments, to the public. PMID:19200833

  15. Comparative performance of a licensed anthrax vaccine versus electroporation based delivery of a PA encoding DNA vaccine in rhesus macaques.

    PubMed

    Livingston, Brian D; Little, Stephen F; Luxembourg, Alain; Ellefsen, Barry; Hannaman, Drew

    2010-01-22

    DNA vaccination is a promising immunization strategy that could be applied in the development of vaccines for a variety of prophylactic and therapeutic indications. Utilizing anthrax protective antigen as a model antigen, we demonstrate that electroporation mediated delivery enhanced the immunogenicity of DNA vaccines in nonhuman primates over 100-fold as compared to conventional intramuscular injection. Two administrations of a DNA vaccine with electroporation elicited anthrax toxin neutralizing antibody responses in 100% of rhesus macaques. Toxin neutralizing antibodies were sustained for the nearly 1-year study duration and were correlated with protection against subsequent lethal Bacillus anthracis spore challenge. Collectively, electroporation mediated DNA vaccination conferred protection comparable to that observed following vaccination with an FDA approved anthrax vaccine.

  16. Vaccine delivery to disease control: a paradigm shift in health policy.

    PubMed

    John, T Jacob; Jain, Yogesh; Nadimpally, Sarojini; Jesani, Amar

    2017-01-01

    India's Universal Immunisation Programme (UIP) has resulted in the creation of infrastructure, human resources and systems for the procurement and delivery of vaccines. Recently, new vaccines have been added and there are plans for the introduction of more. However, the outcomes in terms of reduction of the diseases for which the vaccines are being administered remain ambiguous. This is evident from the persistent health issues that children continue to experience, despite immunisation. This situation raises a fundamental ethical question for public health: vaccinations are one of the tools of disease control, but are they properly aligned to the control of disease so as to produce the expected public health utility or benefit?

  17. Variability in Nose-to-Lung Aerosol Delivery

    PubMed Central

    Walenga, Ross L; Tian, Geng; Hindle, Michael; Yelverton, Joshua; Dodson, Kelley; Longest, P. Worth

    2014-01-01

    Nasal delivery of lung targeted pharmaceutical aerosols is ideal for drugs that need to be administered during high flow nasal cannula (HFNC) gas delivery, but based on previous studies losses and variability through both the delivery system and nasal cavity are expected to be high. The objective of this study was to assess the variability in aerosol delivery through the nose to the lungs with a nasal cannula interface for conventional and excipient enhanced growth (EEG) delivery techniques. A database of nasal cavity computed tomography (CT) scans was collected and analyzed, from which four models were selected to represent a wide range of adult anatomies, quantified based on the nasal surface area-to-volume ratio (SA/V). Computational fluid dynamics (CFD) methods were validated with existing in vitro data and used to predict aerosol delivery through a streamlined nasal cannula and the four nasal models at a steady state flow rate of 30 L/min. Aerosols considered were solid particles for EEG delivery (initial 0.9 μm and 1.5 μm aerodynamic diameters) and conventional droplets (5 μm) for a control case. Use of the EEG approach was found to reduce depositional losses in the nasal cavity by an order of magnitude and substantially reduce variability. Specifically, for aerosol deposition efficiency in the four geometries, the 95% confidence intervals (CI) for 0.9 and 5 μm aerosols were 2.3-3.1 and 15.5-66.3%, respectively. Simulations showed that the use of EEG as opposed to conventional methods improved delivered dose of aerosols through the nasopharynx, expressed as penetration fraction (PF), by approximately a factor of four. Variability of PF, expressed by the coefficient of variation (CV), was reduced by a factor of four with EEG delivery compared with the control case. Penetration fraction correlated well with SA/V for larger aerosols, but smaller aerosols showed some dependence on nasopharyngeal exit hydraulic diameter. In conclusion, results indicated that

  18. CpG Oligodeoxynucleotides Facilitate Delivery of Whole Inactivated H9N2 Influenza Virus via Transepithelial Dendrites of Dendritic Cells in Nasal Mucosa

    PubMed Central

    Qin, Tao; Yin, Yinyan; Yu, Qinghua; Huang, Lulu; Wang, Xiaoqing; Lin, Jian

    2015-01-01

    ABSTRACT The spread of the low-pathogenicity avian H9N2 influenza virus has seriously increased the risk of a new influenza pandemic. Although whole inactivated virus (WIV) vaccine via intranasal pathway is the effective method of blocking virus transmission, the mucosal barrier seems to be a major factor hampering its development. CpG oligodeoxynucleotides, a known adjuvant, can target downstream dendritic cells (DCs) and effectively enhance the mucosal and systemic immune responses. However, the ability of CpGs to assist H9N2 WIV in transepithelial transport remains unknown. Here, in vitro and in vivo, we showed that CpGs provided assistance for H9N2 WIV in recruiting DCs to the nasal epithelial cells (ECs) and forming transepithelial dendrites (TEDs) to capture luminal viruses. CD103+ DCs participated in this process. Chemokine CCL20 from nasal ECs played a key role in driving DC recruitment and TED formation. Virus-loaded DCs quickly migrated into the draining cervical lymph nodes (CLNs) for antigen presentation. In addition, the competence of CpGs was independent of direct epithelial transport via the transcellular or paracellular pathway. Taken together, our data demonstrated that CpGs enhanced the transport of H9N2 WIV via TEDs of nasal DCs, which might be a novel mechanism for optimal adaptive immune responses. IMPORTANCE This paper demonstrates by both an in vivo and an in vitro coculture model that CpG oligodeoxynucleotides, known as an adjuvant generally targeting downstream immune responses, also are crucial for the transport of H9N2 WIV across nasal epithelial cells (ECs) via the uptake of transepithelial dendrites (TEDs). Our results prove for the first time to our knowledge that the immune-potentiating mechanism of CpGs is based on strengthening the transepithelial uptake of H9N2 WIV in nasal mucosa. These findings provide a fresh perspective for further improvement of intranasal influenza vaccines, which are urgently needed in the face of the

  19. Increase in DNA vaccine efficacy by virosome delivery and co-expression of a cytolytic protein.

    PubMed

    Gargett, Tessa; Grubor-Bauk, Branka; Miller, Darren; Garrod, Tamsin; Yu, Stanley; Wesselingh, Steve; Suhrbier, Andreas; Gowans, Eric J

    2014-06-01

    The potential of DNA vaccines has not been realised due to suboptimal delivery, poor antigen expression and the lack of localised inflammation, essential for antigen presentation and an effective immune response to the immunogen. Initially, we examined the delivery of a DNA vaccine encoding a model antigen, luciferase (LUC), to the respiratory tract of mice by encapsulation in a virosome. Virosomes that incorporated influenza virus haemagglutinin effectively delivered DNA to cells in the mouse respiratory tract and resulted in antigen expression and systemic and mucosal immune responses to the immunogen after an intranasal (IN) prime/intradermal (ID) boost regimen, whereas a multidose ID regimen only generated systemic immunity. We also examined systemic immune responses to LUC after ID vaccination with a DNA vaccine, which also encoded one of the several cytolytic or toxic proteins. Although the herpes simplex virus thymidine kinase, in the presence of the prodrug, ganciclovir, resulted in cell death, this failed to increase the humoral or cell-mediated immune responses. In contrast, the co-expression of LUC with the rotavirus non-structural protein 4 (NSP4) protein or a mutant form of mouse perforin, proteins which are directly cytolytic, resulted in increased LUC-specific humoral and cell-mediated immunity. On the other hand, co-expression of LUC with diphtheria toxin subunit A or overexpression of perforin or NSP4 resulted in a lower level of immunity. In summary, the efficacy of DNA vaccines can be improved by targeted IN delivery of DNA or by the induction of cell death in vaccine-targeted cells after ID delivery.

  20. Recent advances in microparticle and nanoparticle delivery vehicles for mucosal vaccination.

    PubMed

    McNeela, E A; Lavelle, E C

    2012-01-01

    The great potential of mucosal vaccination is widely accepted but progress in the clinical development of subunit mucosal vaccines has been disappointing. Of the available approaches, the use of polymer-based microparticles is attractive because these delivery vehicles can be specifically tailored for vaccines and they offer the potential for integration of adjuvant. Here we address recent developments in the use of particulates as mucosal vaccines and the potential of novel targeting strategies, formulation approaches and adjuvant combinations to enhance the efficacy of particle-based mucosal vaccines. This review discusses the current status of mucosal vaccines based on particles and highlights several of the strategies that are currently under investigation for improving their immunogenicity. These include enhancing the stability of formulations in the luminal environment, increasing uptake by specifically targeting particles to mucosal inductive sites, and augmenting immunogenicity through co-formulation with immunostimulatory agents.

  1. Diphtheria toxoid loaded poly-(epsilon-caprolactone) nanoparticles as mucosal vaccine delivery systems.

    PubMed

    Singh, Jasvinder; Pandit, Sreenivas; Bramwell, Vincent W; Alpar, H Oya

    2006-02-01

    Poly-(epsilon-caprolactone) (PCL), a poly(lactide-co-glycolide) (PLGA)-PCL blend and co-polymer nanoparticles encapsulating diphtheria toxoid (DT) were investigated for their potential as a mucosal vaccine delivery system. The nanoparticles, prepared using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method, demonstrated release profiles which were dependent on the properties of the polymers. An in vitro experiment using Caco-2 cells showed significantly higher uptake of PCL nanoparticles in comparison to polymeric PLGA, the PLGA-PCL blend and co-polymer nanoparticles. The highest uptake mediated by the most hydrophobic nanoparticles using Caco-2 cells was mirrored in the in vivo studies following nasal administration. PCL nanoparticles induced DT serum specific IgG antibody responses significantly higher than PLGA. A significant positive correlation between hydrophobicity of the nanoparticles and the immune response was observed following intramuscular administration. The positive correlation between hydrophobicity of the nanoparticles and serum DT specific IgG antibody response was also observed after intranasal administration of the nanoparticles. The cytokine assays showed that the serum IgG antibody response induced is different according to the route of administration, indicated by the differential levels of IL-6 and IFN-gamma. The nanoparticles eliciting the highest IgG antibody response did not necessarily elicit the highest levels of the cytokines IL-6 and IFN-gamma.

  2. Development of Tat-Conjugated Dendrimer for Transdermal DNA Vaccine Delivery.

    PubMed

    Bahadoran, Azadeh; Moeini, Hassan; Bejo, Mohd Hair; Hussein, Mohd Zobir; Omar, Abdul Rahman

    In order to enhance cellular uptake and to facilitate transdermal delivery of DNA vaccine, polyamidoamine (PAMAM) dendrimers conjugated with HIV transactivator of transcription (TAT) was developed. First, the plasmid DNA (pIRES-H5/GFP) nanoparticle was formulated using PAMAM dendrimer and TAT peptide and then characterized for surface charge, particle size, DNA encapsulation and protection of the pIRES-H5/GFP DNA plasmid to enzymatic digestion. Subsequently, the potency of the TAT-conjugated dendrimer for gene delivery was evaluated through in vitro transfection into Vero cells followed by gene expression analysis including western blotting, fluorescent microscopy and PCR. The effect of the TAT peptide on cellular uptake of DNA vaccine was studied by qRT-PCR and flow cytometry. Finally, the ability of TAT-conjugated PAMAM dendrimer for transdermal delivery of the DNA plasmid was assessed through artificial membranes followed by qRT-PCR and flow cytometry. TAT-conjugated PAMAM dendrimer showed the ability to form a compact and nanometre-sized polyplexes with the plasmid DNA, having the size range of 105 to 115 nm and a positive charge of +42 to +45 mV over the N/P ratio of 6:1(+/-).  In vitro transfection analysis into Vero cells confirms the high potency of TAT-conjugated PAMAM dendrimer to enhance the cellular uptake of DNA vaccine.  The permeability value assay through artificial membranes reveals that TAT-conjugated PAMAM has more capacity for transdermal delivery of the DNA compared to unmodified PAMAM dendrimer (P<0.05). The findings of this study suggest that TAT-conjugated PAMAM dendrimer is a promising non-viral vector for transdermal use.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  3. Protective immunity in mice achieved with dry powder formulation and alternative delivery of plague F1-V vaccine.

    PubMed

    Huang, Joanne; D'Souza, Ajit J; Alarcon, Jason B; Mikszta, John A; Ford, Brandi M; Ferriter, Matthew S; Evans, Michelle; Stewart, Todd; Amemiya, Kei; Ulrich, Robert G; Sullivan, Vincent J

    2009-05-01

    The potential use of Yersinia pestis as a bioterror agent is a great concern. Development of a stable powder vaccine against Y. pestis and administration of the vaccine by minimally invasive methods could provide an alternative to the traditional liquid formulation and intramuscular injection. We evaluated a spray-freeze-dried powder vaccine containing a recombinant F1-V fusion protein of Y. pestis for vaccination against plaque in a mouse model. Mice were immunized with reconstituted spray-freeze-dried F1-V powder via intramuscular injection, microneedle-based intradermal delivery, or noninvasive intranasal administration. By intramuscular injection, the reconstituted powder induced serum antibody responses and provided protection against lethal subcutaneous challenge with 1,000 50% lethal doses of Y. pestis at levels equivalent to those elicited by unprocessed liquid formulations (70 to 90% protection). The feasibility of intradermal and intranasal delivery of reconstituted powder F1-V vaccine was also demonstrated. Overall, microneedle-based intradermal delivery was shown to be similar in efficacy to intramuscular injection, while intranasal administration required an extra dose of vaccine to achieve similar protection. In addition, the results suggest that seroconversion against F1 may be a better predictor of protection against Y. pestis challenge than seroconversion against either F1-V or V. In summary, we demonstrate the preclinical feasibility of using a reconstituted powder F1-V formulation and microneedle-based intradermal delivery to provide protective immunity against plague in a mouse model. Intranasal delivery, while feasible, was less effective than injection in this study. The potential use of these alternative delivery methods and a powder vaccine formulation may result in substantial health and economic benefits.

  4. Monodisperse, Uniformly-Shaped Particles for Controlled Respiratory Vaccine Delivery

    NASA Astrophysics Data System (ADS)

    Fromen, Catherine Ann

    The majority of the world's most infectious diseases occur at the air-tissue interface called the mucosa, including HIV/AIDS, tuberculosis, measles, and bacterial or viral gut and respiratory infections. Despite this, vaccines have generally been developed for the systemic immune system and fail to provide protection at the mucosal site. Vaccine delivery directly to the lung mucosa could provide superior lung protection for many infectious diseases, such as TB or influenza, as well as systemic and therapeutic vaccines for diseases such as Dengue fever, asthma, or cancer. Specifically, precision engineered biomaterials are believed to offer tremendous opportunities for a new generation of vaccines. The goal of this approach is to leverage naturally occurring processes of the immune system to produce memory responses capable of rapidly destroy virulent pathogens without harmful exposure. Considerable knowledge of biomaterial properties and their interaction with the immune system of the lung is required for successful translation. The overall goal of this work was to fabricate and characterize nano- and microparticles using the Particle Replication In Non-wetting Templates (PRINT) fabrication technique and optimize them as pulmonary vaccine carriers. (Abstract shortened by ProQuest.).

  5. Aerosol Delivery with Two Nebulizers Through High-Flow Nasal Cannula: A Randomized Cross-Over Single-Photon Emission Computed Tomography-Computed Tomography Study.

    PubMed

    Dugernier, Jonathan; Hesse, Michel; Jumetz, Thibaud; Bialais, Emilie; Roeseler, Jean; Depoortere, Virginie; Michotte, Jean-Bernard; Wittebole, Xavier; Ehrmann, Stephan; Laterre, Pierre-François; Jamar, François; Reychler, Gregory

    2017-10-01

    High-flow nasal cannula use is developing in ICUs. The aim of this study was to compare aerosol efficiency by using two nebulizers through a high-flow nasal cannula: the most commonly used jet nebulizer (JN) and a more efficient vibrating-mesh nebulizer (VN). Aerosol delivery of diethylenetriaminepentaacetic acid labeled with technetium-99m (4 mCi/4 mL) to the lungs by using a VN (Aerogen Solo ® ; Aerogen Ltd., Galway, Ireland) and a constant-output JN (Opti-Mist Plus Nebulizer ® ; ConvaTec, Bridgewater, NJ) through a high-flow nasal cannula (Optiflow ® ; Fisher & Paykel, New Zealand) was compared in six healthy subjects. Flow rate was set at 30 L/min through the heated humidified circuit. Pulmonary and extrapulmonary deposition was measured by single-photon emission computed tomography combined with a low-dose computed tomographic scan and by planar scintigraphy. Lung deposition was only 3.6 (2.1-4.4) and 1 (0.7-2)% of the nominal dose with the VN and the JN, respectively (p < 0.05). The JN showed higher retained doses than the VN. However, both nebulizers were associated with substantial deposition in the single limb circuit, the humidification chamber, and the nasal cannula [58.2 (51.6-61.6)% of the nominal dose with the VN versus 19.2 (15.8-22.9)% of the nominal dose with the JN, p < 0.05] and in the upper respiratory tract [17.6 (13.4-27.9)% of the nominal dose with the VN and 8.6 (6.0-11.0)% of the nominal dose with the JN, p < 0.05], especially in the nasal cavity. In the specific conditions of the study, pulmonary drug delivery through the high-flow nasal cannula is about 1%-4% of the initial amount of drugs placed in the nebulizer, despite the higher efficiency of the VN as compared with the JN.

  6. TLR7 and 9 agonists are highly effective mucosal adjuvants for norovirus virus-like particle vaccines

    PubMed Central

    Hjelm, Brooke E; Kilbourne, Jacquelyn; Herbst-Kralovetz, Melissa M

    2014-01-01

    Virus-like particles (VLPs) are an active area of vaccine research, development and commercialization. Mucosal administration of VLPs provides an attractive avenue for delivery of vaccines with the potential to produce robust immune responses. Nasal and oral delivery routes are particularly intriguing due to differential activation of mucosa-associated lymphoid tissues. We compared both intranasal and oral administration of VLPs with a panel of toll-like receptor (TLR) agonists (TLR3, 5, 7, 7/8, and 9) to determine the mucosal adjuvant activity of these immunomodulators. We selected Norwalk virus (NV) VLPs because it is an effective model antigen and an active area of research and commercialization. To prioritize these adjuvants, VLP-specific antibody production in serum (IgG, IgG1, IgG2a), vaginal lavages (IgG, IgA), and fecal pellets (IgA) were measured across a longitudinal timeseries in vaccinated mice. Additional distal mucosal sites (nasal, brochoalveolar, salivary, and gastrointestinal) were evaluated for VLP-specific responses (IgA). Intranasal co-delivery of VLPs with TLR7 or TLR9 agonists produced the most robust and broad-spectrum immune responses, systemically and at distal mucosal sites inducing VLP-specific antibodies at all sites evaluated. In addition, these VLP-specific antibodies blocked binding of NV VLPs to histo-blood group antigen (H type 1), supporting their functionality. Oral administration and/or other TLR agonists tested in the panel did not consistently enhance VLP-specific immune responses. This study demonstrates that intranasal co-delivery of VLPs with TLR7 or TLR9 agonists provides dose-sparing advantages for induction of specific and functional antibody responses against VLPs (i.e., non-replicating antigens) in the respiratory, gastrointestinal, and reproductive tract. PMID:24280723

  7. Surface-Modified P(HEMA-co-MAA) Nanogel Carriers for Oral Vaccine Delivery: Design, Characterization, and In Vitro Targeting Evaluation

    PubMed Central

    Durán-Lobato, Matilde; Carrillo-Conde, Brenda; Khairandish, Yasmine; Peppas, Nicholas A.

    2015-01-01

    Oral drug delivery is a route of choice for vaccine administration because of its noninvasive nature and thus efforts have focused on efficient delivery of vaccine antigens to mucosal sites. An effective oral vaccine delivery system must protect the antigen from degradation upon mucosal delivery, penetrate mucosal barriers, and control the release of the antigen and costimulatory and immunomodulatory agents to specific immune cells (i.e., APCs). In this paper, mannan-modified pH-responsive P(HEMA-co-MAA) nanogels were synthesized and assessed as carriers for oral vaccination. The nanogels showed pH-sensitive properties, entrapping and protecting the loaded cargo at low pH values, and triggered protein release after switching to intestinal pH values. Surface decoration with mannan as carbohydrate moieties resulted in enhanced internalization by macrophages as well as increasing the expression of relevant costimulatory molecules. These findings indicate that mannan-modified P(HEMA-co-MAA) nanogels are a promising approach to a more efficacious oral vaccination regimen. PMID:24955658

  8. Fabrication, Characterization, In vitro Evaluation of Solid Lipid Nanoemulsion of Flunarizine dihydrochloride for Nasal Delivery.

    PubMed

    Newton, Maria J; Harjot, Kaur

    2017-01-01

    Flunarizine dihydrochloride (FHC) is used for the prophylaxis to migraine. Flunarizine has solubility problems which is practically insoluble in water and alcohol. Nanoemulsion is the approach to increase the solubility of the insoluble drugs. Nanoemulsions of FHC was prepared which can be given through the alternate route such as nasal drug delivery for migraine. In this research work the solubility of the poorly soluble FHC was successfully improved by preparing it as a nano emulsion. Nanoemulsions can pass through the biological membrane easily so it can be delivered through nasal mucosa by which it may provide a quicker onset of action. The currently available dosage forms are in the form of tablet. The formulations were prepared by using Glycerl Monostearate (GMS), Tween 80 as surfactant and PEG 400: Ethanol as co-surfactant in the distilled water. Nanoemulsions were prepared by step by step procedure. The prepared nanoemulsions were analyzed preliminarily by Master Sizer followed by Zeta Sizer by using the technique Dynamic Photon Correlation Spectroscopy. The best nanoemulsion was subjected to Zeta Potential study. The TEM analysis was carried out on the best formulation to gain the detailed information about the formulation. The best formulation was selected based on the physical appearance, homogenecity of the preparation, Preliminary Master Sizer analysis report, Secondary Zeta Sizer analysis report with Zeta Potential and TEM. The best formulation demonstrated the size in nano range with improved solubility. The FHC nano emulsion was prepared successfully which improved the solubility of the drug. The drug release study on simulated nasal fluid revealed that the preparation is suitable to be delivered through the nasal route. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. In situ pneumococcal vaccine production and delivery through a hybrid biological-biomaterial vector

    PubMed Central

    Li, Yi; Beitelshees, Marie; Fang, Lei; Hill, Andrew; Ahmadi, Mahmoud Kamal; Chen, Mingfu; Davidson, Bruce A.; Knight, Paul; Smith, Randall J.; Andreadis, Stelios T.; Hakansson, Anders P.; Jones, Charles H.; Pfeifer, Blaine A.

    2016-01-01

    The type and potency of an immune response provoked during vaccination will determine ultimate success in disease prevention. The basis for this response will be the design and implementation of antigen presentation to the immune system. Whereas direct antigen administration will elicit some form of immunological response, a more sophisticated approach would couple the antigen of interest to a vector capable of broad delivery formats and designed for heightened response. New antigens associated with pneumococcal disease virulence were used to test the delivery and adjuvant capabilities of a hybrid biological-biomaterial vector consisting of a bacterial core electrostatically coated with a cationic polymer. The hybrid design provides (i) passive and active targeting of antigen-presenting cells, (ii) natural and multicomponent adjuvant properties, (iii) dual intracellular delivery mechanisms, and (iv) a simple formulation mechanism. In addition, the hybrid format enables device-specific, or in situ, antigen production and consolidation via localization within the bacterial component of the vector. This capability eliminates the need for dedicated antigen production and purification before vaccination efforts while leveraging the aforementioned features of the overall delivery device. We present the first disease-specific utilization of the vector toward pneumococcal disease highlighted by improved immune responses and protective capabilities when tested against traditional vaccine formulations and a range of clinically relevant Streptococcus pneumoniae strains. More broadly, the results point to similar levels of success with other diseases that would benefit from the production, delivery, and efficacy capabilities offered by the hybrid vector. PMID:27419235

  10. Characterization of guinea pig T cell responses elicited after EP-assisted delivery of DNA vaccines to the skin

    PubMed Central

    Schultheis, Katherine; Schaefer, Hubert; Yung, Bryan S.; Oh, Janet; Muthumani, Karuppiah; Humeau, Laurent; Broderick, Kate E.

    2016-01-01

    The skin is an ideal target tissue for vaccine delivery for a number of reasons. It is highly accessible, and most importantly, enriched in professional antigen presenting cells. Possessing strong similarities to human skin physiology and displaying a defined epidermis, the guinea pig is an appropriate model to study epidermal delivery of vaccine. However, whilst we have characterized the humoral responses in the guinea pig associated with skin vaccine protocols we have yet to investigate the T cell responses. In response to this inadequacy, we developed an IFN-γ ELISpot assay to characterize the cellular immune response in the peripheral blood of guinea pigs. Using a nucleoprotein (NP) influenza pDNA vaccination regimen, we characterized host T cell responses. After delivery of the DNA vaccine to the guinea pig epidermis we detected robust and rapid T cell responses. The levels of IFN-γ spot-forming units averaged approximately 5000 per million cells after two immunizations. These responses were broad in that multiple regions across the NP antigen elicited a T cell response. Interestingly, we identified a number of NP immunodominant T cell epitopes to be conserved across an outbred guinea pig population, a phenomenon which was also observed after immunization with a RSV DNA vaccine. We believe this data enhances our understanding of the cellular immune response elicited to a vaccine in guinea pigs, and globally, will advance the use of this model for vaccine development, especially those targeting skin as a delivery site. PMID:27894716

  11. Oral delivery of human biopharmaceuticals, autoantigens and vaccine antigens bioencapsulated in plant cells

    PubMed Central

    Kwon, Kwang-Chul; Verma, Dheeraj; Singh, Nameirakpam D.; Herzog, Roland; Daniell, Henry

    2012-01-01

    Among 12 billion injections administered annually, unsafe delivery leads to >20 million infections and >100 million reactions. In an emerging new concept, freeze-dried plant cells (lettuce) expressing vaccine antigens/biopharmaceuticals are protected in the stomach from acids/enzymes but are released to the immune or blood circulatory system when plant cell walls are digested by microbes that colonize the gut. Vaccine antigens bioencapsulated in plant cells upon oral delivery after priming, conferred both mucosal and systemic immunity and protection against bacterial, viral or protozoan pathogens or toxin challenge. Oral delivery of autoantigens was effective against complications of type 1diabetes and hemophilia, by developing tolerance. Oral delivery of proinsulin or exendin-4 expressed in plant cells regulated blood glucose levels similar to injections. Therefore, this new platform offers a low cost alternative to deliver different therapeutic proteins to combat infectious or inherited diseases by eliminating inactivated pathogens, expensive purification, cold storage/transportation and sterile injections. PMID:23099275

  12. Costs of vaccine delivery in the Gambia before and after, pentavalent and pneumococcal conjugate vaccine introductions.

    PubMed

    Usuf, E; Mackenzie, G; Lowe-Jallow, Y; Boye, B; Atherly, D; Suraratdecha, C; Griffiths, U K

    2014-04-07

    The Gambia introduced seven-valent pneumococcal conjugate vaccine (PCV) in August 2009 and switched to 13-valent PCV in April 2011. In April 2009 monovalent hepatitis B and combined Diphtheria-Tetanus-Pertussis and Haemophilus influenzae type b vaccines were transitioned to a combined pentavalent vaccine. The current schedule offers three doses of PCV and pentavalent, and continues to give children monovalent hepatitis B vaccine at birth. We estimated the overall costs of the Gambian immunisation programme and the incremental costs of introducing pentavalent and the seven-valent PCV. Twenty health facilities out of a total of 56 were surveyed. Data collected included number of vaccine doses delivered, staff time spent on vaccine delivery, distance travelled to collect vaccines, and cold chain expansion due to new vaccine introduction. National level data were collected from key informant interviews. Annualised costs were calculated in 2009 US$. With a PCV price of US$7 per dose, the incremental costs of introducing PCV was US$1.6 million, equivalent to US$25 per fully immunised child, with systems costs accounting for US$1.90. The switch to pentavalent vaccine resulted in cost savings of US$0.45 per fully immunised child. Total annual costs increased by 45% after the introduction of the new vaccines, amounting to US$ 3.0 million, or US$45 per fully immunised child. Vaccine prices were the most important determinant of total incremental costs and cold chain expansion the biggest cost component of systems costs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Pathogen-mimicking vaccine delivery system designed with a bioactive polymer (inulin acetate) for robust humoral and cellular immune responses.

    PubMed

    Kumar, Sunny; Kesharwani, Siddharth S; Kuppast, Bhimanna; Bakkari, Mohammed Ali; Tummala, Hemachand

    2017-09-10

    New and improved vaccines are needed against challenging diseases such as malaria, tuberculosis, Ebola, influenza, AIDS, and cancer. The majority of existing vaccine adjuvants lack the ability to significantly stimulate the cellular immune response, which is required to prevent the aforementioned diseases. This study designed a novel particulate based pathogen-mimicking vaccine delivery system (PMVDS) to target antigen-presenting-cells (APCs) such as dendritic cells. The uniqueness of PMVDS is that the polymer used to prepare the delivery system, Inulin Acetate (InAc), activates the innate immune system. InAc was synthesized from the plant polysaccharide, inulin. PMVDS provided improved and persistent antigen delivery to APCs as an efficient vaccine delivery system, and simultaneously, activated Toll-Like Receptor-4 (TLR-4) on APCs to release chemokine's/cytokines as an immune-adjuvant. Through this dual mechanism, PMVDS robustly stimulated both the humoral (>32 times of IgG1 levels vs alum) and the cell-mediated immune responses against the encapsulated antigen (ovalbumin) in mice. More importantly, PMVDS stimulated both cytotoxic T cells and natural killer cells of cell-mediated immunity to provide tumor (B16-ova-Melanoma) protection in around 40% of vaccinated mice and significantly delayed tumor progression in rest of the mice. PMVDS is a unique bio-active vaccine delivery technology with broader applications for vaccines against cancer and several intracellular pathogens, where both humoral and cellular immune responses are desired. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Preparation and in vitro characterization of thermosensitive and mucoadhesive hydrogels for nasal delivery of phenylephrine hydrochloride.

    PubMed

    Xu, Xiaofeng; Shen, Yan; Wang, Wei; Sun, Chunmeng; Li, Chang; Xiong, Yerong; Tu, Jiasheng

    2014-11-01

    The aim of the present work was to develop a nasal delivery system of phenylephrine hydrochloride (PE) in spray form to make prolonged remedy of nasal congestion. The formulations contain the thermosensitive hydrogel, i.e., Poloxamer 407 (P407) and Poloxamer 188 (P188) mixtures, and mucoadhesives, i.e., ε-polylysine (ε-PL) and low molecular weight sodium hyaluronate (MW 11,000Da). The in vitro characterizations of formulations including rheology studies, texture profiles and in vitro mucoadhesion potential were investigated after gelation temperatures measurements. The results showed that the concentration of P407 or P188 had significant influence on gelation temperature and texture profiles. The addition of mucoadhesives, though lowered the gel strength of formulations, increased interaction with mucin. After screening, two formulations (i.e., 1.0% PE/0.5% ε-PL/17% P407/0.5% P188 or Formulation A; and 1.0% PE/0.5% HA/17% P407/0.8% P188 or Formulation B) presenting suitable gelation temperatures (∼32°C) were used for further studies on in vitro release behaviors and mucosa ciliotoxicity. Both formulations showed sustained release of PE for up to 8h and similar toxicity to saline, the negative control. Thus, the thermosensitive and mucoadhesive PE-containing hydrogels are promising to achieve prolonged decongestion in nasal cavity. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Anti-cancer vaccination by transdermal delivery of antigen peptide-loaded nanogels via iontophoresis.

    PubMed

    Toyoda, Mao; Hama, Susumu; Ikeda, Yutaka; Nagasaki, Yukio; Kogure, Kentaro

    2015-04-10

    Transdermal vaccination with cancer antigens is expected to become a useful anti-cancer therapy. However, it is difficult to accumulate enough antigen in the epidermis for effective exposure to Langerhans cells because of diffusion into the skin and muscle. Carriers, such as liposomes and nanoparticles, may be useful for the prevention of antigen diffusion. Iontophoresis, via application of a small electric current, is a noninvasive and efficient technology for transdermal drug delivery. Previously, we succeeded in the iontophoretic transdermal delivery of liposomes encapsulating insulin, and accumulation of polymer-based nanoparticle nanogels in the stratum corneum of the skin. Therefore, in the present study, we examined the use of iontophoresis with cancer antigen gp-100 peptide KVPRNQDWL-loaded nanogels for anti-cancer vaccination. Iontophoresis resulted in the accumulation of gp-100 peptide and nanogels in the epidermis, and subsequent increase in the number of Langerhans cells in the epidermis. Moreover, tumor growth was significantly suppressed by iontophoresis of the antigen peptide-loaded nanogels. Thus, iontophoresis of the antigen peptide-loaded nanogels may serve as an effective transdermal delivery system for anti-cancer vaccination. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Cluster Randomized Trial of a Toolkit and Early Vaccine Delivery to Improve Childhood Influenza Vaccination Rates in Primary Care

    PubMed Central

    Zimmerman, Richard K.; Nowalk, Mary Patricia; Lin, Chyongchiou Jeng; Hannibal, Kristin; Moehling, Krissy K.; Huang, Hsin-Hui; Matambanadzo, Annamore; Troy, Judith; Allred, Norma J.; Gallik, Greg; Reis, Evelyn C.

    2014-01-01

    Purpose To increase childhood influenza vaccination rates using a toolkit and early vaccine delivery in a randomized cluster trial. Methods Twenty primary care practices treating children (range for n=536-8,183) were randomly assigned to Intervention and Control arms to test the effectiveness of an evidence-based practice improvement toolkit (4 Pillars Toolkit) and early vaccine supplies for use among disadvantaged children on influenza vaccination rates among children 6 months-18 years. Follow-up staff meetings and surveys were used to assess use and acceptability of the intervention strategies in the Intervention arm. Rates for the 2010-2011 and 2011-2012 influenza seasons were compared. Two-level generalized linear mixed modeling was used to evaluate outcomes. Results Overall increases in influenza vaccination rates were significantly greater in the Intervention arm (7.9 percentage points) compared with the Control arm (4.4 percentage points; P<0.034). These rate changes represent 4522 additional doses in the Intervention arm vs. 1,390 additional doses in the Control arm. This effect of the intervention was observed despite the fact that rates increased significantly in both arms - 8/10 Intervention (P<0.001) and 7/10 Control sites (P-values 0.04 to <0.001). Rates in two Intervention sites with pre-intervention vaccination rates >58% did not significantly increase. In regression analyses, a child's likelihood of being vaccinated was significantly higher with: younger age, white race (Odds ratio [OR]=1.29; 95% confidence interval [CI]=1.23-1.34), having commercial insurance (OR=1.30; 95%CI=1.25-1.35), higher pre-intervention practice vaccination rate (OR=1.25; 95%CI=1.16-1.34), and being in the Intervention arm (OR=1.23; 95%CI=1.01-1.50). Early delivery of influenza vaccine was rated by Intervention practices as an effective strategy for raising rates. Conclusions Implementation of a multi-strategy toolkit and early vaccine supplies can significantly improve

  17. Multilayer engineered nanoliposomes as a novel tool for oral delivery of lipopeptide-based vaccines against group A Streptococcus.

    PubMed

    Marasini, Nirmal; Giddam, Ashwini K; Ghaffar, Khairunnisa A; Batzloff, Michael R; Good, Michael F; Skwarczynski, Mariusz; Toth, Istvan

    2016-05-01

    To develop an oral nanovaccine delivery system for lipopeptide-based vaccine candidate against group A Streptococcus. Lipid-core peptide-1-loaded nanoliposomes were prepared as a template and coated with opposite-charged polyelectrolytes to produce particles with size <200 nm. Efficacy of this oral nanovaccine delivery system was evaluated in mice model. Polymer-coated liposomes produced significantly higher antigen-specific mucosal IgA and systemic IgG titers in comparison to vaccine formulated with a strong mucosal adjuvant upon oral immunization in mice. Moreover, high levels of systemic antibody titers were retained even at day 185 postprimary immunization. Efficient oral delivery platform for lipopeptide-based vaccines has been developed.

  18. Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine

    PubMed Central

    Hong, Xiaoyun; Wei, Liangming; Wu, Fei; Wu, Zaozhan; Chen, Lizhu; Liu, Zhenguo; Yuan, Weien

    2013-01-01

    Microneedles were first conceptualized for drug delivery many decades ago, overcoming the shortages and preserving the advantages of hypodermic needle and conventional transdermal drug-delivery systems to some extent. Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. This review describes microneedle geometry and the representative dissolving and biodegradable microneedle delivery methods via the skin, followed by the fabricating methods. Finally, this review puts forward some perspectives that require further investigation. PMID:24039404

  19. Characterization of guinea pig T cell responses elicited after EP-assisted delivery of DNA vaccines to the skin.

    PubMed

    Schultheis, Katherine; Schaefer, Hubert; Yung, Bryan S; Oh, Janet; Muthumani, Karuppiah; Humeau, Laurent; Broderick, Kate E; Smith, Trevor R F

    2017-01-03

    The skin is an ideal target tissue for vaccine delivery for a number of reasons. It is highly accessible, and most importantly, enriched in professional antigen presenting cells. Possessing strong similarities to human skin physiology and displaying a defined epidermis, the guinea pig is an appropriate model to study epidermal delivery of vaccine. However, whilst we have characterized the humoral responses in the guinea pig associated with skin vaccine protocols we have yet to investigate the T cell responses. In response to this inadequacy, we developed an IFN-γ ELISpot assay to characterize the cellular immune response in the peripheral blood of guinea pigs. Using a nucleoprotein (NP) influenza pDNA vaccination regimen, we characterized host T cell responses. After delivery of the DNA vaccine to the guinea pig epidermis we detected robust and rapid T cell responses. The levels of IFN-γ spot-forming units averaged approximately 5000 per million cells after two immunizations. These responses were broad in that multiple regions across the NP antigen elicited a T cell response. Interestingly, we identified a number of NP immunodominant T cell epitopes to be conserved across an outbred guinea pig population, a phenomenon which was also observed after immunization with a RSV DNA vaccine. We believe this data enhances our understanding of the cellular immune response elicited to a vaccine in guinea pigs, and globally, will advance the use of this model for vaccine development, especially those targeting skin as a delivery site. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Development of an intradermal DNA vaccine delivery strategy to achieve single-dose immunity against respiratory syncytial virus.

    PubMed

    Smith, Trevor R F; Schultheis, Katherine; Morrow, Matthew P; Kraynyak, Kimberly A; McCoy, Jay R; Yim, Kevin C; Muthumani, Karuppiah; Humeau, Laurent; Weiner, David B; Sardesai, Niranjan Y; Broderick, Kate E

    2017-05-15

    Respiratory syncytial virus (RSV) is a massive medical burden in infants, children and the elderly worldwide, and an effective, safe RSV vaccine remains an unmet need. Here we assess a novel vaccination strategy based on the intradermal delivery of a SynCon® DNA-based vaccine encoding engineered RSV-F antigen using a surface electroporation device (SEP) to target epidermal cells, in clinically relevant experimental models. We demonstrate the ability of this strategy to elicit robust immune responses. Importantly we demonstrate complete resistance to pulmonary infection at a single low dose of vaccine in the cotton rat RSV/A challenge model. In contrast to the formalin-inactivated RSV (FI-RSV) vaccine, there was no enhanced lung inflammation upon virus challenge after DNA vaccination. In summary the data presented outline the pre-clinical development of a highly efficacious, tolerable and safe non-replicating vaccine delivery strategy. Copyright © 2017. Published by Elsevier Ltd.

  1. Vaccine decision-making begins in pregnancy: Correlation between vaccine concerns, intentions and maternal vaccination with subsequent childhood vaccine uptake.

    PubMed

    Danchin, M H; Costa-Pinto, J; Attwell, K; Willaby, H; Wiley, K; Hoq, M; Leask, J; Perrett, K P; O'Keefe, Jacinta; Giles, M L; Marshall, H

    2017-08-12

    Maternal and childhood vaccine decision-making begins prenatally. Amongst pregnant Australian women we aimed to ascertain vaccine information received, maternal immunisation uptake and attitudes and concerns regarding childhood vaccination. We also aimed to determine any correlation between a) intentions and concerns regarding childhood vaccination, (b) concerns about pregnancy vaccination, (c) socioeconomic status (SES) and (d) uptake of influenza and pertussis vaccines during pregnancy and routine vaccines during childhood. Women attending public antenatal clinics were recruited in three Australian states. Surveys were completed on iPads. Follow-up phone surveys were done three to six months post delivery, and infant vaccination status obtained via the Australian Childhood Immunisation Register (ACIR). Between October 2015 and March 2016, 975 (82%) of 1184 mothers consented and 406 (42%) agreed to a follow up survey, post delivery. First-time mothers (445; 49%) had significantly more vaccine concerns in pregnancy and only 73% had made a decision about childhood vaccination compared to 89% of mothers with existing children (p-value<0.001). 66% of mothers reported receiving enough information during pregnancy on childhood vaccination. In the post delivery survey, 46% and 82% of mothers reported receiving pregnancy influenza and pertussis vaccines respectively. The mother's degree of vaccine hesitancy and two attitudinal factors were correlated with vaccine uptake post delivery. There was no association between reported maternal vaccine uptake or SES and childhood vaccine uptake. First time mothers are more vaccine hesitant and undecided about childhood vaccination, and only two thirds of all mothers believed they received enough information during pregnancy. New interventions to improve both education and communication on childhood and maternal vaccines, delivered by midwives and obstetricians in the Australian public hospital system, may reduce vaccine hesitancy

  2. Intranasal delivery of a protein subunit vaccine using a Tobacco Mosaic Virus platform protects against pneumonic plague.

    PubMed

    Arnaboldi, Paul M; Sambir, Mariya; D'Arco, Christina; Peters, Lauren A; Seegers, Jos F M L; Mayer, Lloyd; McCormick, Alison A; Dattwyler, Raymond J

    2016-11-11

    Yersinia pestis, one of history's deadliest pathogens, has killed millions over the course of human history. It has attributes that make it an ideal choice to produce mass casualties and is a prime candidate for use as a biological weapon. When aerosolized, Y. pestis causes pneumonic plague, a pneumonia that is 100% lethal if not promptly treated with effective antibiotics. Currently, there is no FDA approved plague vaccine. The current lead vaccine candidate, a parenterally administered protein subunit vaccine comprised of the Y. pestis virulence factors, F1 and LcrV, demonstrated variable levels of protection in primate pneumonic plague models. As the most likely mode of exposure in biological attack with Y. pestis is by aerosol, this raises a question of whether this parenteral vaccine will adequately protect humans against pneumonic plague. In the present study we evaluated two distinct mucosal delivery platforms for the intranasal (IN) administration of LcrV and F1 vaccine proteins, a live bacterial vector, Lactobacillus plantarum, and a Tobacco Mosaic Virus (TMV) based delivery platform. IN administration of L. plantarum expressing LcrV, or TMV-conjugated to LcrV and F1 (TMV-LcrV+TMV-F1) resulted in the similar induction of high titers of IgG antibodies and evidence of proinflammatory cytokine secretion. However, only the TMV-conjugate delivery platform protected against subsequent lethal challenge with Y. pestis. TMV-LcrV+TMV-F1 co-vaccinated mice had no discernable morbidity and no mortality, while mice vaccinated with L. plantarum expressing LcrV or rLcrV+rF1 without TMV succumbed to infection or were only partially protected. Thus, TMV is a suitable mucosal delivery platform for an F1-LcrV subunit vaccine that induces complete protection against pneumonic infection with a lethal dose of Y. pestis in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Degradable polymeric nano-films and particles as delivery platforms for vaccines and immunotherapeutics

    NASA Astrophysics Data System (ADS)

    Su, Xingfang

    Degradable polymeric materials provide opportunities for the development of improved vaccines and immunotherapies by acting as platforms that facilitate the delivery of molecules to appropriate tissue and cellular locations to achieve therapeutic outcomes. To this end, we have designed and characterized nano-films and particles employing a hydrolytically degradable polymer for the delivery of vaccine antigens and immunotherapeutics. We first describe protein- and oligonucleotide-loaded layer-by-layer (LbL)-assembled multilayer thin films constructed based on electrostatic interactions between a cationic poly(beta-amino ester) (PBAE, denoted Poly-1) with a model protein antigen, ovalbumin (OVA), and/or immunostimulatory CpG oligonucleotides for transcutaneous delivery. Linear growth of nanoscale Poly-I/OVA bilayers was observed. Dried OVA protein-loaded films rapidly deconstructed when rehydrated in saline solutions, releasing OVA as non-aggregated/non-degraded protein, suggesting that the structure of biomolecules integrated into these multilayer films are preserved during release. Using confocal fluorescence microscopy and an in vivo murine ear skin model, we demonstrated delivery of OVA from LbL films into barrier-disrupted skin, uptake of the protein by skin-resident antigen-presenting cells (Langerhans cells), and transport of the antigen to the skin-draining lymph nodes. Dual incorporation of OVA and CpG oligonucleotides into the nanolayers of LbL films enabled dual release of the antigen and adjuvant with distinct kinetics for each component; OVA was rapidly released while CpG was released in a relatively sustained manner. Applied as skin patches, these films delivered OVA and CpG to Langerhans Cells in the skin. To our knowledge, this is the first demonstration of LbL films applied for the delivery of biomolecules into skin. This approach provides a new route for storage of vaccines and other immunotherapeutics in a solid-state thin film for subsequent

  4. Influence of the pneumococcal conjugate vaccines on the temporal variation of pneumococcal carriage and the nasal microbiota in healthy infants: a longitudinal analysis of a case-control study.

    PubMed

    Mika, Moana; Maurer, Josua; Korten, Insa; Allemann, Aurélie; Aebi, Suzanne; Brugger, Silvio D; Qi, Weihong; Frey, Urs; Latzin, Philipp; Hilty, Markus

    2017-07-24

    Bacterial colonization of the upper airways is a prerequisite for subsequent invasive disease. With the introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13), changes in pneumococcal upper airway colonization have been described. It is, however, less evident whether the vaccines lead to compositional changes of the upper airway microbiota. Here, we performed a case-control study using samples from a longitudinal infant cohort from Switzerland. We compared pneumococcal carriage and the nasal microbiota within the first year of life of healthy infants vaccinated with either PCV7 (n = 20, born in 2010) or PCV13 (n = 21, born between 2011 and 2013). Nasal swabs were collected every second week (n = 763 in total). Pneumococcal carriage was analyzed by quantitative PCR of the pneumococcal-specific lytA gene. Analysis of the bacterial core microbiota was performed based on 16S rRNA sequencing and subsequent oligotyping. We exclusively performed oligotyping of the core microbiota members, which were defined as the five most abundant bacterial families (Moraxellaceae, Streptococcaceae, Staphylococcaceae, Corynebacteriaceae, and Pasteurellaceae). Linear mixed effect (LME) and negative binomial regression models were used for statistical analyses. We found a higher number of samples positive for pneumococcal carriage in PCV7- compared to PCV13-vaccinated infants (LME model; P = 0.01). In contrast, infants vaccinated in the PCV13 era had an increased alpha diversity as measured by the richness and the Shannon Diversity Index (LME model; P = 0.003 and P = 0.01, respectively). Accordingly, the PCV13 era was associated with clusters of a higher diversity than PCV7-associated clusters. Furthermore, infants vaccinated with PCV13 had a higher binary-based within-subject microbiota similarity, as well as a decreased Jensen-Shannon distance over time as compared to PCV7-vaccinated infants, indicating a higher microbiota stability in the PCV

  5. Estimating the costs of the vaccine supply chain and service delivery for selected districts in Kenya and Tanzania.

    PubMed

    Mvundura, Mercy; Lorenson, Kristina; Chweya, Amos; Kigadye, Rosemary; Bartholomew, Kathryn; Makame, Mohammed; Lennon, T Patrick; Mwangi, Steven; Kirika, Lydia; Kamau, Peter; Otieno, Abner; Murunga, Peninah; Omurwa, Tom; Dafrossa, Lyimo; Kristensen, Debra

    2015-05-28

    Having data on the costs of the immunization system can provide decision-makers with information to benchmark the costs when evaluating the impact of new technologies or programmatic innovations. This paper estimated the supply chain and immunization service delivery costs and cost per dose in selected districts in Kenya and Tanzania. We also present operational data describing the supply chain and service delivery points (SDPs). To estimate the supply chain costs, we collected resource-use data for the cold chain, distribution system, and health worker time and per diems paid. We also estimated the service delivery costs, which included the time cost of health workers to provide immunization services, and per diems and transport costs for outreach sessions. Data on the annual quantities of vaccines distributed to each facility, and the occurrence and duration of stockouts were collected from stock registers. These data were collected from the national store, 2 regional and 4 district stores, and 12 SDPs in each country for 2012. Cost per dose for the supply chain and immunization service delivery were estimated. The average annual costs per dose at the SDPs were $0.34 (standard deviation (s.d.) $0.18) for Kenya when including only the vaccine supply chain costs, and $1.33 (s.d. $0.82) when including immunization service delivery costs. In Tanzania, these costs were $0.67 (s.d. $0.35) and $2.82 (s.d. $1.64), respectively. Both countries experienced vaccine stockouts in 2012, bacillus Calmette-Guérin vaccine being more likely to be stocked out in Kenya, and oral poliovirus vaccine in Tanzania. When stockouts happened, they usually lasted for at least one month. Tanzania made investments in 2011 in preparation for planned vaccine introductions, and their supply chain cost per dose is expected to decline with the new vaccine introductions. Immunization service delivery costs are a significant portion of the total costs at the SDPs. Copyright © 2015 Elsevier Ltd. All

  6. Incremental costs of introducing jet injection technology for delivery of routine childhood vaccinations: comparative analysis from Brazil, India, and South Africa.

    PubMed

    Griffiths, Ulla K; Santos, Andreia C; Nundy, Neeti; Jacoby, Erica; Matthias, Dipika

    2011-01-29

    Disposable-syringe jet injectors (DSJIs) have the potential to deliver vaccines safely and affordably to millions of children around the world. We estimated the incremental costs of transitioning from needles and syringes to delivering childhood vaccines with DSJIs in Brazil, India, and South Africa. Two scenarios were assessed: (1) DSJI delivery of all vaccines at current dose and depth; (2) a change to intradermal (ID) delivery with DSJIs for hepatitis B and yellow fever vaccines, while the other vaccines are delivered by DSJIs at current dose and depth. The main advantage of ID delivery is that only a small fraction of the standard dose may be needed to obtain an immune response similar to that of subcutaneous or intramuscular injection. Cost categories included were vaccines, injection equipment, waste management, and vaccine transport. Some delivery cost items, such as training and personnel were excluded as were treatment cost savings caused by a reduction in diseases transmitted due to unsafe injections. In the standard dose and depth scenario, the incremental costs of introducing DSJIs per fully vaccinated child amount to US$ 0.57 in Brazil, US$ 0.65 in India and US$ 1.24 in South Africa. In the ID scenario, there are cost savings of US$ 0.11 per child in Brazil, and added costs of US$ 0.45 and US$ 0.76 per child in India and South Africa, respectively. The most important incremental cost item is jet injector disposable syringes. The incremental costs should be evaluated against other vaccine delivery technologies that can deliver the same benefits to patients, health care workers, and the community. DSJIs deserve consideration by global and national decision-makers as a means to expand access to ID delivery and to enhance safety at marginal additional cost. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Nasal delivery of chitosan-coated poly(lactide-co-glycolide)-encapsulated honeybee (Apis mellifera) venom promotes Th 1-specific systemic and local intestinal immune responses in weaned pigs.

    PubMed

    Lee, Jin-A; Kim, Yun-Mi; Kim, Tae-Hoon; Lee, Sang-Ho; Lee, Cho-A; Cho, Cheong-Weon; Jeon, Jong-Woon; Park, Jin-Kyu; Kim, Sang-Ki; Jung, Bock-Gie; Lee, Bong-Joo

    2016-10-01

    Nasal delivery is a convenient and acceptable route for drug administration, and has been shown to elicit a much more potent local and systemic response compared with other drug delivery routes. We previously demonstrated that rectal administration of poly(lactide-co-glycolide)-encapsulated honeybee venom (P-HBV) could enhance systemic Th 1-specific immune responses. We therefore synthesized chitosan-coated P-HBV (CP-HBV) and then evaluated the immune-boosting efficacy of nasally administered CP-HBV on systemic and local intestinal immunity compared with non-chitosan-coated P-HBV. The nasally delivered CP-HBV effectively enhanced Th 1-specific responses, eliciting a significant increase in the CD3(+)CD4(+)CD8(-) Th cell population, lymphocyte proliferation capacity, and expression of Th 1 cytokines (IFN-γ, IL-12, and IL-2) in peripheral blood mononuclear cells. Furthermore, these immune-boosting effects persisted up to 21days post CP-HBV administration. Nasal administration of CP-HBV also led to an increase of not only the CD4(+) Th 1 and IFN-γ secreting CD4(+) Th 1 cell population but also Th 1-specific cytokines and transcription factors, including IL-12, IFN-γ, STAT4, and T-bet, in isolated mononuclear cells from the spleen and ileum. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. A Novel Vaccine Delivery Model of the Apicomplexan Eimeria tenella Expressing Eimeria maxima Antigen Protects Chickens against Infection of the Two Parasites

    PubMed Central

    Tang, Xinming; Liu, Xianyong; Yin, Guangwen; Suo, Jingxia; Tao, Geru; Zhang, Sixin; Suo, Xun

    2018-01-01

    Vaccine delivery is critical in antigen discovery and vaccine efficacy and safety. The diversity of infectious diseases in humans and livestock has required the development of varied delivery vehicles to target different pathogens. In livestock animals, previous strategies for the development of coccidiosis vaccines have encountered several hurdles, limiting the development of multiple species vaccine formulations. Here, we describe a novel vaccine delivery system using transgenic Eimeria tenella expressing immunodominant antigens of Eimeria maxima. In this delivery system, the immune mapped protein 1 of E. maxima (EmIMP1) was delivered by the closely related species of E. tenella to the host immune system during the whole endogenous life cycle. The overexpression of the exogenous antigen did not interfere with the reproduction and immunogenicity of transgenic Eimeria. After immunization with the transgenic parasite, we detected EmIMP1’s and E. maxima oocyst antigens’ specific humoral and cellular immune responses. In particular, we observed partial protection of chickens immunized with transgenic E. tenella against subsequent E. maxima infections. Our results demonstrate that the transgenic Eimeria parasite is an ideal coccidia antigen delivery vehicle and represents a new type of coccidiosis vaccines. In addition, this model could potentially be used in the development of malaria live sporozoite vaccines, in which antigens from different strains can be expressed in the vaccine strain. PMID:29375584

  9. A Novel Vaccine Delivery Model of the Apicomplexan Eimeria tenella Expressing Eimeria maxima Antigen Protects Chickens against Infection of the Two Parasites.

    PubMed

    Tang, Xinming; Liu, Xianyong; Yin, Guangwen; Suo, Jingxia; Tao, Geru; Zhang, Sixin; Suo, Xun

    2017-01-01

    Vaccine delivery is critical in antigen discovery and vaccine efficacy and safety. The diversity of infectious diseases in humans and livestock has required the development of varied delivery vehicles to target different pathogens. In livestock animals, previous strategies for the development of coccidiosis vaccines have encountered several hurdles, limiting the development of multiple species vaccine formulations. Here, we describe a novel vaccine delivery system using transgenic Eimeria tenella expressing immunodominant antigens of Eimeria maxima . In this delivery system, the immune mapped protein 1 of E. maxima (EmIMP1) was delivered by the closely related species of E. tenella to the host immune system during the whole endogenous life cycle. The overexpression of the exogenous antigen did not interfere with the reproduction and immunogenicity of transgenic Eimeria . After immunization with the transgenic parasite, we detected EmIMP1's and E. maxima oocyst antigens' specific humoral and cellular immune responses. In particular, we observed partial protection of chickens immunized with transgenic E. tenella against subsequent E. maxima infections. Our results demonstrate that the transgenic Eimeria parasite is an ideal coccidia antigen delivery vehicle and represents a new type of coccidiosis vaccines. In addition, this model could potentially be used in the development of malaria live sporozoite vaccines, in which antigens from different strains can be expressed in the vaccine strain.

  10. School-based vaccination programmes: a systematic review of the evidence on organisation and delivery in high income countries.

    PubMed

    Perman, Sarah; Turner, Simon; Ramsay, Angus I G; Baim-Lance, Abigail; Utley, Martin; Fulop, Naomi J

    2017-03-14

    Many countries have recently expanded their childhood immunisation programmes. Schools are an increasingly attractive setting for delivery of these new immunisations because of their ability to reach large numbers of children in a short period of time. However, there are organisational challenges to delivery of large-scale vaccination programmes in schools. Understanding the facilitators and barriers is important for improving the delivery of future school-based vaccination programmes. We undertook a systematic review of evidence on school-based vaccination programmes in order to understand the influence of organisational factors on the delivery of programmes. Our eligibility criteria were studies that (1) focused on childhood or adolescent vaccination programmes delivered in schools; (2) considered organisational factors that influenced the preparation or delivery of programmes; (3) were conducted in a developed or high-income country; and (4) had been peer reviewed. We searched for articles published in English between 2000 and 2015 using MEDLINE and HMIC electronic databases. Additional studies were identified by searching the Cochrane Library and bibliographies. We extracted data from the studies, assessed quality and the risk of bias, and categorised findings using a thematic framework of eight organisational factors. We found that most of the recent published literature is from the United States and is concerned with the delivery of pandemic or seasonal flu vaccination programmes at a regional (state) or local level. We found that the literature is largely descriptive and not informed by the use of theory. Despite this, we identified common factors that influence the implementation of programmes. These factors included programme leadership and governance, organisational models and institutional relationships, workforce capacity and roles particularly concerning the school nurse, communication with parents and students, including methods for obtaining consent

  11. Human papillomavirus vaccine delivery strategies that achieved high coverage in low- and middle-income countries.

    PubMed

    LaMontagne, D Scott; Barge, Sandhya; Le, Nga Thi; Mugisha, Emmanuel; Penny, Mary E; Gandhi, Sanjay; Janmohamed, Amynah; Kumakech, Edward; Mosqueira, N Rocio; Nguyen, Nghi Quy; Paul, Proma; Tang, Yuxiao; Minh, Tran Hung; Uttekar, Bella Patel; Jumaan, Aisha O

    2011-11-01

    To assess human papillomavirus (HPV) vaccination coverage after demonstration projects conducted in India, Peru, Uganda and Viet Nam by PATH and national governments and to explore the reasons for vaccine acceptance or refusal. Vaccines were delivered through schools or health centres or in combination with other health interventions, and either monthly or through campaigns at fixed time points. Using a two-stage cluster sample design, the authors selected households in demonstration project areas and interviewed over 7000 parents or guardians of adolescent girls to assess coverage and acceptability. They defined full vaccination as the receipt of all three vaccine doses and used an open-ended question to explore acceptability. Vaccination coverage in school-based programmes was 82.6% (95% confidence interval, CI: 79.3-85.6) in Peru, 88.9% (95% CI: 84.7-92.4) in 2009 in Uganda and 96.1% (95% CI: 93.0-97.8) in 2009 in Viet Nam. In India, a campaign approach achieved 77.2% (95% CI: 72.4-81.6) to 87.8% (95% CI: 84.3-91.3) coverage, whereas monthly delivery achieved 68.4% (95% CI: 63.4-73.4) to 83.3% (95% CI: 79.3-87.3) coverage. More than two thirds of respondents gave as reasons for accepting the HPV vaccine that: (i) it protects against cervical cancer; (ii) it prevents disease, or (iii) vaccines are good. Refusal was more often driven by programmatic considerations (e.g. school absenteeism) than by opposition to the vaccine. High coverage with HPV vaccine among young adolescent girls was achieved through various delivery strategies in the developing countries studied. Reinforcing positive motivators for vaccine acceptance is likely to facilitate uptake.

  12. Exploitation of Langerhans cells for in vivo DNA vaccine delivery into the lymph nodes.

    PubMed

    Tőke, E R; Lőrincz, O; Csiszovszki, Z; Somogyi, E; Felföldi, G; Molnár, L; Szipőcs, R; Kolonics, A; Malissen, B; Lori, F; Trocio, J; Bakare, N; Horkay, F; Romani, N; Tripp, C H; Stoitzner, P; Lisziewicz, J

    2014-06-01

    There is no clinically available cancer immunotherapy that exploits Langerhans cells (LCs), the epidermal precursors of dendritic cells (DCs) that are the natural agent of antigen delivery. We developed a DNA formulation with a polymer and obtained synthetic 'pathogen-like' nanoparticles that preferentially targeted LCs in epidermal cultures. These nanoparticles applied topically under a patch-elicited robust immune responses in human subjects. To demonstrate the mechanism of action of this novel vaccination strategy in live animals, we assembled a high-resolution two-photon laser scanning-microscope. Nanoparticles applied on the native skin poorly penetrated and poorly induced LC motility. The combination of nanoparticle administration and skin treatment was essential both for efficient loading the vaccine into the epidermis and for potent activation of the LCs to migrate into the lymph nodes. LCs in the epidermis picked up nanoparticles and accumulated them in the nuclear region demonstrating an effective nuclear DNA delivery in vivo. Tissue distribution studies revealed that the majority of the DNA was targeted to the lymph nodes. Preclinical toxicity of the LC-targeting DNA vaccine was limited to mild and transient local erythema caused by the skin treatment. This novel, clinically proven LC-targeting DNA vaccine platform technology broadens the options on DC-targeting vaccines to generate therapeutic immunity against cancer.

  13. Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines.

    PubMed

    Meseda, Clement A; Atukorale, Vajini; Kuhn, Jordan; Schmeisser, Falko; Weir, Jerry P

    2016-01-01

    The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification). The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1) elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that MVA and MVA

  14. Vaccine delivery management.

    PubMed

    Cheyne, J

    1989-01-01

    During the typical 12- to 18-month voyage of a vaccine from manufacturer to immunization site, many situations arise in which the cold chain may be interrupted. Extensive efforts have been made in the 1980s to ensure an uninterrupted cold chain through the use of improved equipment and better training of personnel. One important advance is the vaccine cold-chain monitor, which identifies weak spots in the cold chain and prevents the use of heat-damaged vaccine. Further improvements will require efforts by the recipient countries (e.g., better use of the private sector for transport and equipment management), by donor agencies (e.g., greater consideration of the operational and maintenance costs of the equipment selected and resolution of fuel shortages), and by industry (e.g., more appropriate packaging and pricing of vaccine, extension of the expiration period, and increased heat stability.

  15. In vivo investigation of twin-screw extruded lipid implants for vaccine delivery.

    PubMed

    Even, Marie-Paule; Young, Katie; Winter, Gerhard; Hook, Sarah; Engert, Julia

    2014-07-01

    Sustained release systems have become the focus of attention in vaccine delivery as they may reduce or prevent the need for repeated dosing. In this work, lipid implants were prepared by twin-screw extrusion and investigated as vaccine delivery systems in vivo. The lipid implants consisted of cholesterol, soybean lecithin, and Dynasan 114. Ovalbumin (OVA) was employed as a model antigen and Quil-A (QA) as an adjuvant. In addition, OVA and QA loaded liposomes were prepared by the lipid-film hydration method, freeze-dried and then added to the lipid matrix prior to extrusion. Implants were administered subcutaneously and the kinetics of antigen release as well as the overall immune response stimulated were analysed by measuring CD4(+) and CD8(+) T cell proliferation, OVA-specific IgG production as well as cytokine (IFN-γ and IL4) secretion. Vaccine release from the implants was completed by 14 days. Inclusion of adjuvant into the implants was required for the generation of cellular and humoral immune responses. Inclusion of liposomes into the implant did not enhance the resulting immune responses generated. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Human papillomavirus vaccine delivery strategies that achieved high coverage in low- and middle-income countries

    PubMed Central

    Barge, Sandhya; Le, Nga Thi; Mugisha, Emmanuel; Penny, Mary E; Gandhi, Sanjay; Janmohamed, Amynah; Kumakech, Edward; Mosqueira, N Rocio; Nguyen, Nghi Quy; Paul, Proma; Tang, Yuxiao; Minh, Tran Hung; Uttekar, Bella Patel; Jumaan, Aisha O

    2011-01-01

    Abstract Objective To assess human papillomavirus (HPV) vaccination coverage after demonstration projects conducted in India, Peru, Uganda and Viet Nam by PATH and national governments and to explore the reasons for vaccine acceptance or refusal. Methods Vaccines were delivered through schools or health centres or in combination with other health interventions, and either monthly or through campaigns at fixed time points. Using a two-stage cluster sample design, the authors selected households in demonstration project areas and interviewed over 7000 parents or guardians of adolescent girls to assess coverage and acceptability. They defined full vaccination as the receipt of all three vaccine doses and used an open-ended question to explore acceptability. Findings Vaccination coverage in school-based programmes was 82.6% (95% confidence interval, CI: 79.3–85.6) in Peru, 88.9% (95% CI: 84.7–92.4) in 2009 in Uganda and 96.1% (95% CI: 93.0–97.8) in 2009 in Viet Nam. In India, a campaign approach achieved 77.2% (95% CI: 72.4–81.6) to 87.8% (95% CI: 84.3–91.3) coverage, whereas monthly delivery achieved 68.4% (95% CI: 63.4–73.4) to 83.3% (95% CI: 79.3–87.3) coverage. More than two thirds of respondents gave as reasons for accepting the HPV vaccine that: (i) it protects against cervical cancer; (ii) it prevents disease, or (iii) vaccines are good. Refusal was more often driven by programmatic considerations (e.g. school absenteeism) than by opposition to the vaccine. Conclusion High coverage with HPV vaccine among young adolescent girls was achieved through various delivery strategies in the developing countries studied. Reinforcing positive motivators for vaccine acceptance is likely to facilitate uptake. PMID:22084528

  17. Immunomodulatory properties of vitamins, flavonoids and plant oils and their potential as vaccine adjuvants and delivery systems.

    PubMed

    Vajdy, Michael

    2011-11-01

    During the past century, vaccinologists have attempted to mimic pathogens in their immune-enhancing capacity. This led to the development of life-saving vaccines based on live attenuated viruses, bacteria and toxoids. Hence, intense research in vaccine adjuvant discovery has focused on toll like receptors, mutant toxins and viral and bacterial vectors. Nutritive components such as vitamins and select polyphenols also possess immunomodulating properties without the potential toxic and adverse side effects of agents that mimic danger signals. This review pertains to immunomodulatory properties of nutritive components, that is vitamins A, C, D, E, flavonoids and plant oils, as potential vaccine adjuvants and delivery systems, covering Pubmed publication searches from 1980 through 2011. This relatively unexplored field of the potential of nutritive components as vaccine adjuvants holds great promise to promote the development of effective and above all safe vaccines. Hence the future focus should be placed on enhancing their efficacy, mainly through novel approaches in designing structural derivatives, formulations, delivery systems and routes of administration. As safety has been the major issue in development of novel vaccines, this new approach will probably result in new discoveries in designing safe and effective vaccines.

  18. Estimating the cost of cholera-vaccine delivery from the societal point of view: A case of introduction of cholera vaccine in Bangladesh.

    PubMed

    Sarker, Abdur Razzaque; Islam, Ziaul; Khan, Iqbal Ansary; Saha, Amit; Chowdhury, Fahima; Khan, Ashraful Islam; Cravioto, Alejandro; Clemens, John David; Qadri, Firdausi; Khan, Jahangir A M

    2015-09-11

    Cholera is a major global public health problem that causes both epidemic and endemic disease. The World Health Organization recommends oral cholera vaccines as a public health tool in addition to traditional prevention practices and treatments in both epidemic and endemic settings. In many developing countries like Bangladesh, the major issue concerns the affordability of this vaccine. In February 2011, a feasibility study entitled, "Introduction of Cholera Vaccine in Bangladesh (ICVB)", was conducted for a vaccination campaign using inactivated whole-cell cholera vaccine (Shanchol) in a high risk area of Mirpur, Dhaka. Empirical data obtained from this trial was used to determine the vaccination cost for a fully immunized person from the societal perspective. A total of 123,661 people were fully vaccinated receiving two doses of the vaccine, while 18,178 people received one dose of the same vaccine. The total cost for vaccine delivery was US$ 492,238 giving a total vaccination cost per fully-vaccinated individual of US$ 3.98. The purchase cost of the vaccine accounted for 58% of the overall cost of vaccination. Attempts to reduce the per-dose cost of the vaccine are likely to have a large impact on the cost of similar vaccination campaigns in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Potential of polymeric particles as future vaccine delivery systems/adjuvants for parenteral and non-parenteral immunization against tuberculosis: A systematic review.

    PubMed

    Khademi, Farzad; Derakhshan, Mohammad; Yousefi-Avarvand, Arshid; Tafaghodi, Mohsen

    2018-02-01

    Production of effective tuberculosis (TB) vaccine is necessity. However, the development of new subunit vaccines is faced with concerns about their weak immunogenicity. To overcome such problems, polymers-based vaccine delivery systems have been proposed to be used via various routes. The purpose of this study was to determine the potential of polymeric particles as future vaccine delivery systems/adjuvants for parenteral and non-parenteral immunization against TB. PubMed, Scopus, Science-Direct, and the ISI web of knowledge databases were searched for related keywords. A total of 420 articles, written up to June 25, 2016, were collected on the potential of polymeric particles as TB vaccine delivery systems after parenteral and non-parenteral immunization. Thirty-one relevant articles were selected by applying inclusion and exclusion criteria. It was shown that the immunogenicity of TB vaccines had been improved by using biodegradable and non-biodegradable synthetic polymers as well as natural polymers and they are better able to enhance the humoral and cellular immune responses, compared to TB vaccines alone. The present study revealed that various polymeric particles, after M. tuberculosis challenge in animal models, provide long-lasting protection against TB. PLGA (poly (lactide-co-glycolide)) and chitosan polymers were widely used as TB vaccine delivery systems/adjuvants. It seems that PLGA and chitosan polymers are well-suited particles for the parenteral and non-parenteral administration of TB vaccines, respectively. Non-biodegradable synthetic polymers in comparison with biodegradable synthetic and natural polymers have been used less frequently. Therefore, further study on this category of polymers is required.

  20. Comparison of vaccine efficacy for different antigen delivery systems for infectious pancreatic necrosis virus vaccines in Atlantic salmon (Salmo salar L.) in a cohabitation challenge model.

    PubMed

    Munang'andu, Hetron M; Fredriksen, Børge N; Mutoloki, Stephen; Brudeseth, Bjørn; Kuo, Tsun-Yung; Marjara, Inderjit S; Dalmo, Roy A; Evensen, Øystein

    2012-06-08

    Two strains of IPNV made by reverse genetics on the Norwegian Sp strain NVI-015 (GenBank AY379740) backbone encoding the virulent (T(217)A(221)) and avirulent (P(217)T(221)) motifs were used to prepare inactivated whole virus (IWV), nanoparticle vaccines with whole virus, Escherichia coli subunit encoding truncated VP2-TA and VP2-PT, VP2-TA and VP2-PT fusion antigens with putative translocating domains of Pseudomonas aeruginosa exotoxin, and plasmid DNA encoding segment A of the TA strain. Post challenge survival percentages (PCSP) showed that IWV vaccines conferred highest protection (PCSP=42-53) while nanoparticle, sub-unit recombinant and DNA vaccines fell short of the IWV vaccines in Atlantic salmon (Salmo salar L.) postsmolts challenged with the highly virulent Sp strain NVI-015 (TA strain) of IPNV after 560 degree days post vaccination. Antibody levels induced by these vaccines did not show antigenic differences between the virulent and avirulent motifs for vaccines made with the same antigen dose and delivery system after 8 weeks post vaccination. Our findings show that fish vaccinated with less potent vaccines comprising of nanoparticle, DNA and recombinant vaccines got infected much earlier and yielded to higher infection rates than fish vaccinated with IWV vaccines that were highly potent. Ability of the virulent (T(217)A(221)) and avirulent (P(217)T(221)) motifs to limit establishment of infection showed equal protection for vaccines made of the same antigen dose and delivery systems. Prevention of tissue damage linked to viral infection was eminent in the more potent vaccines than the less protective ones. Hence, there still remains the challenge of developing highly efficacious vaccines with the ability to eliminate the post challenge carrier state in IPNV vaccinology. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Potential Cost-Effectiveness of an Influenza Vaccination Program Offering Microneedle Patch for Vaccine Delivery in Children.

    PubMed

    Wong, Carlos; Jiang, Minghuan; You, Joyce H S

    2016-01-01

    The influenza vaccine coverage rate of children is low in Hong Kong. Microneedle patches (MNPs) is a technology under development for painless delivery of vaccines. This study aimed to examine the potential clinical outcomes and direct medical costs of an influenza program offering MNP vaccine to children who have declined intramuscular (IM) vaccine in Hong Kong. A decision model was designed to compare potential outcomes between IM vaccine program and a program offering MNP vaccine to those declined IM vaccine (IM/MNP program) in a hypothetical cohort of children over one-year time horizon. The model outcomes included direct medical cost, influenza infection rate, mortality rate, and quality-adjusted life-years (QALYs) loss. Model inputs were retrieved from published literature. Sensitivity analyses were performed to examine the robustness of model results. In base-case analysis, IM/MNP program was more costly per child (USD19.13 versus USD13.69; USD1 = HKD7.8) with lower influenza infection rate (98.9 versus 124.8 per 1,000 children), hospitalization rate (0.83 versus 1.05 per 1,000 children) and influenza-related mortality rate (0.00042 versus 0.00052 per 1,000 children) when compared to IM program. The incremental cost per QALY saved (ICER) of IM/MNP program versus IM program was 27,200 USD/QALY. Using gross domestic product (GDP) per capita of Hong Kong (USD40,594) as threshold of willingness-to-pay (WTP) per QALY, one-way sensitivity analysis found ICER of IM/MNP to exceed WTP when duration of illness in outpatient setting was <5.7 days or cost per MNP vaccine was >1.39-time of IM vaccine cost. In 10,000 Monte Carlo simulations, IM/MNP program was the preferred option in 57.28% and 91.68% of the time, using 1x and 3x GDP per capita as WTP threshold, respectively. Acceptance of IM/MNP program as the preferred program was subject to the WTP threshold, duration of illness in outpatient settings, and cost of MNP vaccine.

  2. Thiolated polycarbophil as an adjuvant for permeation enhancement in nasal delivery of antisense oligonucleotides.

    PubMed

    Vetter, A; Martien, R; Bernkop-Schnürch, A

    2010-03-01

    The purpose of this study was to investigate the effect of thiolated polycarbophil as an adjuvant to enhance the permeation and improve the stability of a phosphorothioate antisense oligonucleotide (PTO-ODN) on the nasal mucosa. Polycarbophil-cysteine (PCP-Cys) was synthesized by the covalent attachment of L-cysteine to the polymeric backbone. Cytotoxicity tests were examined on human nasal epithelial cells from surgery of nasal polyps confirmed by histological studies. Deoxyribonuclease I activity in respiratory region of the porcine nasal cavity was analyzed by an enzymatic assay. The enzymatic degradation of PTO-ODNs on freshly excised porcine nasal mucosa was analyzed and protection of PCP-cysteine toward DNase I degradation was evaluated. Permeation studies were performed in Ussing-type diffusion chambers. PCP-Cys/GSH did not arise a remarkable mortal effect. Porcine respiratory mucosa was shown to possess nuclease activity corresponding to 0.69 Kunitz units/mL. PTO-ODNs were degraded by incubation with nasal mucosa. In the presence of 0.45% thiolated polycarbophil and 0.5% glutathione (GSH), this degradation process could be lowered. In the presence of thiolated polycarbophil and GSH the uptake of PTO-ODNs from the nasal mucosa was 1.7-fold improved. According to these results thiolated polycarbophil/GSH might be a promising excipient for nasal administration of PTO-ODNs. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

  3. Innovative vaccine delivery strategies in response to a cholera outbreak in the challenging context of Lake Chilwa. A rapid qualitative assessment.

    PubMed

    Heyerdahl, Leonard W; Ngwira, Bagrey; Demolis, Rachel; Nyirenda, Gabriel; Mwesawina, Maurice; Rafael, Florentina; Cavailler, Philippe; Bernard Le Gargasson, Jean; Mengel, Martin A; Gessner, Bradford D; Guillermet, Elise

    2017-11-07

    A reactive campaign using two doses of Shanchol Oral Cholera Vaccine (OCV) was implemented in 2016 in the Lake Chilwa Region (Malawi) targeting fish dependent communities. Three strategies for the second vaccine dose delivery (including delivery by a community leader and self-administration) were used to facilitate vaccine access. This assessment collected vaccine perceptions and opinions about the OCV campaign of 313 study participants, including: fishermen, fish traders, farmers, community leaders, and one health and one NGO officer. Socio-demographic surveys were conducted, In Depth Interviews and Focus Group Discussions were conducted before and during the campaign. Some fishermen perceived the traditional delivery strategy as reliable but less practical. Delivery by traditional leaders was acceptable for some participants while others worried about traditional leaders not being trained to deliver vaccines or beneficiaries taking doses on their own. A slight majority of beneficiaries considered the self-administration strategy practical while some beneficiaries worried about storing vials outside of the cold chain or losing vials. During the campaign, a majority of participants preferred receiving oral vaccines instead of injections given ease of intake and lack of pain. OCV was perceived as efficacious and safe. However, a lack of information on how sero-protection may be delayed and the degree of sero-protection led to loss of trust in vaccine potency among some participants who witnessed cholera cases among vaccinated individuals. OCV campaign implementation requires accompanying communication on protective levels, less than 100% vaccine efficacy, delays in onset of sero-protection, and out of cold chain storage. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Engineered hybrid spider silk particles as delivery system for peptide vaccines.

    PubMed

    Lucke, Matthias; Mottas, Inès; Herbst, Tina; Hotz, Christian; Römer, Lin; Schierling, Martina; Herold, Heike M; Slotta, Ute; Spinetti, Thibaud; Scheibel, Thomas; Winter, Gerhard; Bourquin, Carole; Engert, Julia

    2018-07-01

    The generation of strong T-cell immunity is one of the main challenges for the development of successful vaccines against cancer and major infectious diseases. Here we have engineered spider silk particles as delivery system for a peptide-based vaccination that leads to effective priming of cytotoxic T-cells. The recombinant spider silk protein eADF4(C16) was fused to the antigenic peptide from ovalbumin, either without linker or with a cathepsin cleavable peptide linker. Particles prepared from the hybrid proteins were taken up by dendritic cells, which are essential for T-cell priming, and successfully activated cytotoxic T-cells, without signs of immunotoxicity or unspecific immunostimulatory activity. Upon subcutaneous injection in mice, the particles were taken up by dendritic cells and accumulated in the lymph nodes, where immune responses are generated. Particles from hybrid proteins containing a cathepsin-cleavable linker induced a strong antigen-specific proliferation of cytotoxic T-cells in vivo, even in the absence of a vaccine adjuvant. We thus demonstrate the efficacy of a new vaccine strategy using a protein-based all-in-one vaccination system, where spider silk particles serve as carriers with an incorporated peptide antigen. Our study further suggests that engineered spider silk-based vaccines are extremely stable, easy to manufacture, and readily customizable. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Safety and Immunogenicity of a Shigella flexneri 2a Invaplex 50 Intranasal Vaccine in Adult Volunteers

    DTIC Science & Technology

    2010-06-01

    stained using methodology described by Hansel [24]. Semi-quantitative scoring of eosinophilia [25] was as follows: no cells, O; few scattered cells or...with local exam findings of nasal discharge, hyperemia. and/or edema. Exploratory analyses of nasal cytology showed pre-vaccination nasal eosinophilia ...et al. Global burden of Shigella infections: implications for vaccine devel- opment and implementation of control strategies. Bull World Health Organ

  6. Development of an acid-resistant Salmonella Typhi Ty21a attenuated vector for improved oral vaccine delivery

    USDA-ARS?s Scientific Manuscript database

    The licensed oral, live-attenuated bacterial vaccine for typhoid fever, Salmonella Typhi strain Ty21a, has also been utilized as a vaccine delivery platform for expression of diverse foreign antigens that stimulate protection against shigellosis, anthrax, plague, or human papilloma virus. However, T...

  7. Localized mucosal response to intranasal live attenuated influenza vaccine in adults.

    PubMed

    Barría, Maria Ines; Garrido, Jose Luis; Stein, Cheryl; Scher, Erica; Ge, Yongchao; Engel, Stephanie M; Kraus, Thomas A; Banach, David; Moran, Thomas M

    2013-01-01

    Influenza virus infection is a major public health burden worldwide. Available vaccines include the inactivated intramuscular trivalent vaccine and, more recently, an intranasal live attenuated influenza vaccine (LAIV). The measure of successful vaccination with the inactivated vaccine is a systemic rise in immunoglobulin G (IgG) level, but for the LAIV no such correlate has been established. Seventy-nine subjects were given the LAIV FluMist. Blood was collected prior to vaccination and 3 days and 30 days after vaccination. Nasal wash was collected 3 days and 30 days after vaccination. Responses were measured systemically and in mucosal secretions for cytokines, cell activation profiles, and antibody responses. Only 9% of subjects who received LAIV seroconverted, while 33% of patients developed at least a 2-fold increase in influenza virus-specific immunoglobulin A (IgA) antibodies in nasal wash. LAIV induced a localized inflammation, as suggested by increased expression of interferon-response genes in mucosal RNA and increased granulocyte colony-stimulating factor (G-CSF) and IP-10 in nasal wash. Interestingly, patients who seroconverted had significantly lower serum levels of G-CSF before vaccination. Protection by LAIV is likely provided through mucosal IgA and not by increases in systemic IgG. LAIV induces local inflammation. Seroconversion is achieved in a small fraction of subjects with a lower serum G-CSF level.

  8. Macromolecular systems for vaccine delivery.

    PubMed

    MuŽíková, G; Laga, R

    2016-10-20

    Vaccines have helped considerably in eliminating some life-threatening infectious diseases in past two hundred years. Recently, human medicine has focused on vaccination against some of the world's most common infectious diseases (AIDS, malaria, tuberculosis, etc.), and vaccination is also gaining popularity in the treatment of cancer or autoimmune diseases. The major limitation of current vaccines lies in their poor ability to generate a sufficient level of protective antibodies and T cell responses against diseases such as HIV, malaria, tuberculosis and cancers. Among the promising vaccination systems that could improve the potency of weakly immunogenic vaccines belong macromolecular carriers (water soluble polymers, polymer particels, micelles, gels etc.) conjugated with antigens and immunistumulatory molecules. The size, architecture, and the composition of the high molecular-weight carrier can significantly improve the vaccine efficiency. This review includes the most recently developed (bio)polymer-based vaccines reported in the literature.

  9. Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery

    PubMed Central

    Best, Simon R.; Peng, Shiwen; Juang, Chi-Mou; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.; Pai, Sara I.

    2009-01-01

    DNA vaccines are an attractive approach to eliciting antigen-specific immunity. Intracellular targeting of tumor antigens through its linkage to immunostimulatory molecules such as calreticulin (CRT) can improve antigen processing and presentation through the MHC Class I pathway and increase cytotoxic CD8+ T cell production. However, even with these enhancements, the efficacy of such immunotherapeutic strategies is dependent on the identification of an effective route and method of DNA administration. Electroporation and gene gun-mediated particle delivery are leading methods of DNA vaccine delivery that can generate protective and therapeutic levels of immune responses in experimental models. In this study, we perform a head-to-head comparison of three methods of vaccination – conventional intramuscular injection, electroporation mediated intramuscular delivery, and epidermal gene gun-mediated particle delivery - in the ability to generate antigen specific cytotoxic CD8+ T cell responses as well as anti-tumor immune responses against an HPV-16 E7 expressing tumor cell line using the pNGVL4a-CRT/E7(detox) DNA vaccine. Vaccination via electroporation generated the highest number of E7-specific cytotoxic CD8+ T cells, which correlated to improved outcomes in the treatment of growing tumors. In addition, we demonstrate that electroporation results in significantly higher levels of circulating protein compared to gene gun or intramuscular vaccination, which likely enhances calreticulin’s role as a local tumor anti-angiogenesis agent. We conclude that electroporation is a promising method for delivery of HPV DNA vaccines and should be considered for DNA vaccine delivery in human clinical trials. PMID:19622402

  10. Regional deposition of nasal sprays in adults: A wide ranging computational study.

    PubMed

    Kiaee, Milad; Wachtel, Herbert; Noga, Michelle L; Martin, Andrew R; Finlay, Warren H

    2018-05-01

    The present work examines regional deposition within the nose for nasal sprays over a large and wide ranging parameter space by using numerical simulation. A set of 7 realistic adult nasal airway geometries was defined based on computed tomography images. Deposition in 6 regions of each nasal airway geometry (the vestibule, valve, anterior turbinate, posterior turbinate, olfactory, and nasopharynx) was determined for varying particle diameter, spray cone angle, spray release direction, particle injection speed, and particle injection location. Penetration of nasal spray particles through the airway geometries represented unintended lung exposure. Penetration was found to be relatively insensitive to injection velocity, but highly sensitive to particle size. Penetration remained at or above 30% for particles exceeding 10 μm in diameter for several airway geometries studied. Deposition in the turbinates, viewed as desirable for both local and systemic nasal drug delivery, was on average maximized for particles ranging from ~20 to 30 μm in diameter, and for low to zero injection velocity. Similar values of particle diameter and injection velocity were found to maximize deposition in the olfactory region, a potential target for nose-to-brain drug delivery. However, olfactory deposition was highly variable between airway geometries, with maximum olfactory deposition ranging over 2 orders of magnitude between geometries. This variability is an obstacle to overcome if consistent dosing between subjects is to be achieved for nose-to-brain drug delivery. Copyright © 2018 John Wiley & Sons, Ltd.

  11. The expanding role of aerosols in systemic drug delivery, gene therapy, and vaccination.

    PubMed

    Laube, Beth L

    2005-09-01

    Aerosolized medications have been used for centuries to treat respiratory diseases. Until recently, inhalation therapy focused primarily on the treatment of asthma and chronic obstructive pulmonary disease, and the pressurized metered-dose inhaler was the delivery device of choice. However, the role of aerosol therapy is clearly expanding beyond that initial focus. This expansion has been driven by the Montreal protocol and the need to eliminate chlorofluorocarbons (CFCs) from traditional metered-dose inhalers, by the need for delivery devices and formulations that can efficiently and reproducibly target the systemic circulation for the delivery of proteins and peptides, and by developments in medicine that have made it possible to consider curing lung diseases with aerosolized gene therapy and preventing epidemics of influenza and measles with aerosolized vaccines. Each of these drivers has contributed to a decade or more of unprecedented research and innovation that has altered how we think about aerosol delivery and has expanded the role of aerosol therapy into the fields of systemic drug delivery, gene therapy, and vaccination. During this decade of innovation, we have witnessed the coming of age of dry powder inhalers, the development of new soft mist inhalers, and improved pressurized metered-dose inhaler delivery as a result of the replacement of CFC propellants with hydrofluoroalkane. The continued expansion of the role of aerosol therapy will probably depend on demonstration of the safety of this route of administration for drugs that have their targets outside the lung and are administered long term (eg, insulin aerosol), on the development of new drugs and drug carriers that can efficiently target hard-to-reach cell populations within the lungs of patients with disease (eg, patients with cystic fibrosis or lung cancer), and on the development of devices that improve aerosol delivery to infants, so that early intervention in disease processes with aerosol

  12. Influence of deposition and spray pattern of nasal powders on insulin bioavailability.

    PubMed

    Pringels, E; Callens, C; Vervaet, C; Dumont, F; Slegers, G; Foreman, P; Remon, J P

    2006-03-09

    The influence of the deposition pattern and spray characteristics of nasal powder formulations on the insulin bioavailability was investigated in rabbits. The formulations were prepared by freeze drying a dispersion containing a physical mixture of drum dried waxy maize starch (DDWM)/Carbopol 974P (90/10, w/w) or a spray-dried mixture of Amioca starch/Carbopol 974P (25/75, w/w). The deposition in the nasal cavity of rabbits and in a silicone human nose model after actuation of three nasal delivery devices (Monopowder, Pfeiffer and experimental system) was compared and related to the insulin bioavailability. Posterior deposition of the powder formulation in the nasal cavity lowered the insulin bioavailability. To study the spray pattern, the shape and cross-section of the emitted powder cloud were analysed. It was concluded that the powder bulk density of the formulation influenced the spray pattern. Consequently, powders of different bulk density were prepared by changing the solid fraction of the freeze dried dispersion and by changing the freezing rate during freeze drying. After nasal delivery of these powder formulations no influence of the powder bulk density and of the spray pattern on the insulin bioavailability was observed.

  13. Surface-Modified Nanocarriers for Nose-to-Brain Delivery: From Bioadhesion to Targeting

    PubMed Central

    Clementino, Adryana; Buttini, Francesca; Colombo, Gaia; Pescina, Silvia; Stanisçuaski Guterres, Silvia; Nicoli, Sara

    2018-01-01

    In the field of nasal drug delivery, nose-to-brain delivery is among the most fascinating applications, directly targeting the central nervous system, bypassing the blood brain barrier. Its benefits include dose lowering and direct brain distribution of potent drugs, ultimately reducing systemic side effects. Recently, nasal administration of insulin showed promising results in clinical trials for the treatment of Alzheimer’s disease. Nanomedicines could further contribute to making nose-to-brain delivery a reality. While not disregarding the need for devices enabling a formulation deposition in the nose’s upper part, surface modification of nanomedicines appears the key strategy to optimize drug delivery from the nasal cavity to the brain. In this review, nanomedicine delivery based on particle engineering exploiting surface electrostatic charges, mucoadhesive polymers, or chemical moieties targeting the nasal epithelium will be discussed and critically evaluated in relation to nose-to-brain delivery. PMID:29543755

  14. Potent Immunity to Low Doses of Influenza Vaccine by Probabilistic Guided Micro-Targeted Skin Delivery in a Mouse Model

    PubMed Central

    Prow, Tarl W.; Crichton, Michael L.; Fairmaid, Emily J.; Roberts, Michael S.; Frazer, Ian H.; Brown, Lorena E.; Kendall, Mark A. F.

    2010-01-01

    Background Over 14 million people die each year from infectious diseases despite extensive vaccine use [1]. The needle and syringe—first invented in 1853—is still the primary delivery device, injecting liquid vaccine into muscle. Vaccines could be far more effective if they were precisely delivered into the narrow layer just beneath the skin surface that contains a much higher density of potent antigen-presenting cells (APCs) essential to generate a protective immune response. We hypothesized that successful vaccination could be achieved this way with far lower antigen doses than required by the needle and syringe. Methodology/Principal Findings To meet this objective, using a probability-based theoretical analysis for targeting skin APCs, we designed the Nanopatch™, which contains an array of densely packed projections (21025/cm2) invisible to the human eye (110 µm in length, tapering to tips with a sharpness of <1000 nm), that are dry-coated with vaccine and applied to the skin for two minutes. Here we show that the Nanopatches deliver a seasonal influenza vaccine (Fluvax® 2008) to directly contact thousands of APCs, in excellent agreement with theoretical prediction. By physically targeting vaccine directly to these cells we induced protective levels of functional antibody responses in mice and also protection against an influenza virus challenge that are comparable to the vaccine delivered intramuscularly with the needle and syringe—but with less than 1/100th of the delivered antigen. Conclusions/Significance Our results represent a marked improvement—an order of magnitude greater than reported by others—for injected doses administered by other delivery methods, without reliance on an added adjuvant, and with only a single vaccination. This study provides a proven mathematical/engineering delivery device template for extension into human studies—and we speculate that successful translation of these findings into humans could uniquely assist with

  15. Opportunity for catch-up HPV vaccination in young women after first delivery.

    PubMed

    Rama, Cristina Helena; Villa, Luisa L; Pagliusi, Sonia; Andreoli, Maria A; Costa, Maria C; Thomann, Patricia; Alves, Venancio A F; Longatto-Filho, Adhemar; Eluf-Neto, Jose

    2010-07-01

    Early age at first delivery has been identified as a risk factor for high-risk HPV-type infection and cervical cancer development. A cross-sectional study was carried out in a large public maternity hospital in São Paulo, Brazil. During June 2006 to February 2007, 301 women aged 15-24 years who gave birth to their first child were recruited between 43 and 60 days after delivery. Detection of HPV DNA in cervical specimens was performed using a standardised PCR protocol with PGMY09/11 primers. The association of selected factors with HPV infection was assessed by using a Generalised Linear Model. HPV DNA was detected in 58.5% (95% CI 52.7% to 64.0%) of the enrolled young women. The most common types of HPV found were: HPV16, HPV51, HPV52, HPV58 and HPV71. The overall prevalence of HPV types targeted by the HPV prophylactic vaccines was: HPV 16-12.0%, HPV 18- 2.3% and HPV 6 and 11 4.3%. In the multivariate analysis, only age (inversely, p for trend=0.02) and smoking habits were independently associated with HPV infection. The findings show that these young primiparous women had high cervical HPV prevalence, suggesting that this is a high-risk group for cervical cancer development. Nevertheless, 17.3% were positive for any of the four HPV types included in HPV vaccines (HPV6, 11, 16 or 18), with 13.3% positive for HPV 16 or 18 and only 1.0% having both vaccine related-oncogenic HPV types. Thus, young primiparous women could benefit from catch-up HPV vaccination programmes.

  16. Conjugating influenza a (H1N1) antigen to n-trimethylaminoethylmethacrylate chitosan nanoparticles improves the immunogenicity of the antigen after nasal administration.

    PubMed

    Liu, Qingfeng; Zheng, Xiaoyao; Zhang, Chi; Shao, Xiayan; Zhang, Xi; Zhang, Qizhi; Jiang, Xinguo

    2015-11-01

    As one of the most serious infectious respiratory diseases, influenza A (H1N1) is a great threat to human health, and it has created an urgent demand for effective vaccines. Nasal immunization can induce both systemic and mucosal immune responses against viruses, and it can serve as an ideal route for vaccination. However, the low immunogenicity of antigens on nasal mucosa is a high barrier for the development of nasal vaccines. In this study, we covalently conjugated an influenza A (H1N1) antigen to the surface of N-trimethylaminoethylmethacrylate chitosan (TMC) nanoparticles (H1N1-TMC/NP) through thioester bonds to increase the immunogenicity of the antigen after nasal administration. SDS-PAGE revealed that most of the antigen was conjugated on TMC nanoparticles, and an in vitro biological activity assay confirmed the stability of the antigen after conjugation. After three nasal immunizations, the H1N1-TMC/NP induced significantly higher levels of serum IgG and mucosal sIgA compared with free antigen. A hemagglutination inhibition assay showed that H1N1-TMC/NP induced much more protective antibodies than antigen-encapsulated nanoparticles or alum-precipitated antigen (I.M.). In the mechanistic study, H1N1-TMC/NP was shown to stimulate macrophages to produce IL-1β and IL-6 and to stimulate spleen lymphocytes to produce IL-2 and IFN-γ. These results indicated that H1N1-TMC/NP may be an effective vaccine against influenza A (H1N1) viruses for use in nasal immunization. © 2015 Wiley Periodicals, Inc.

  17. Ternary particles for effective vaccine delivery to the pulmonary system

    NASA Astrophysics Data System (ADS)

    Terry, Treniece La'shay

    Progress in the fields of molecular biology and genomics has provided great insight into the pathogenesis of disease and the defense mechanisms of the immune system. This knowledge has lead to the classification of an array of abnormal genes, for which, treatment relies on cellular expression of proteins. The utility of DNA-based vaccines hold great promise for the treatment of genetically based and infectious diseases, which ranges from hemophilia, cystic fibrosis, and HIV. Synthetic delivery systems consisting of cationic polymers, such as polyethylenimine (PEI), are capable of condensing DNA into compact structures, maximizing cellular uptake of DNA and yielding high levels of protein expression. To date, short term expression is a major obstacle in the development of gene therapies and has halted their expansion in clinical applications. This study intends to develop a sustained release vaccine delivery system using PLA-PEG block copolymers encapsulating PEI:DNA polyplexes. To enhance the effectiveness of such DNA-based vaccines, resident antigen presenting cells, macrophages and dendritic cells, will be targeted within the alveoli regions of the lungs. Porous microspheres will be engineered with aerodynamic properties capable of achieving deep lung deposition. A fabrication technique using concentric nozzles will be developed to produce porous microspheres. It was observed that modifications in the dispersed to continuous phase ratios have the largest influence on particle size distributions, release rates and encapsulation efficiency which ranged form 80--95% with fourteen days of release. Amphiphilic block copolymers were also used to fabricate porous microspheres. The confirmation of PEG within the biodegradable polymer backbone was found to have a tremendous impact on the microsphere morphology and encapsulation efficiency which varied from 50--90%. Porous microspheres were capable of providing sustained gene expression when tested in vitro using the

  18. Histological and anatomical structure of the nasal cavity of Bama minipigs

    PubMed Central

    Yang, Jingjing; Dai, Lei; Yu, Qinghua; Yang, Qian

    2017-01-01

    Objective The nasal mucosa is equipped with abundant lymphatic tissues, serving as the first line of defense against invasion by microorganisms. In this study, we characterized the features of the nasal mucosa of Bama minipigs (Sus scrofa domestica) via histological analysis. Methods Five cross sections (I, II, III, IV, and V) were obtained from the distal end of the nasal cavity toward the pharynx (along the cavity axis) and examined. Specifically, CD3+ T cells, immunoglobulin A (IgA)+ cells, and M cells were detected by immunohistochemistry, while dendritic cells (DCs) were detected by immunofluorescence. The distribution of goblet cells was determined by periodic acid-Schiff (PAS) staining. Results The nasal cavity of Bama minipigs can be divided into three parts: the regio vestibularis (I, II), regio respiratoria (III, IV), and regio olfactoria (V). Lymphoid tissue was present at random locations in the nasal cavity. Abundant lymphoid tissue was located in the roof of the nasopharyngeal meatus and was continuous with the lymphoid tissue of the pharynx. The distribution of CD3+ T cells, IgA+ cells, M cells, and DCs increased distally in the nasal cavity. Conclusions The present work comprises a histological study of the nasal cavity of Bama minipigs, and will be beneficial for understanding the mechanisms of immunity in these animals after nasal vaccination. PMID:28339502

  19. The blood-brain barrier and nasal drug delivery to the central nervous system.

    PubMed

    Miyake, Marcel Menon; Bleier, Benjamin S

    2015-01-01

    The blood-brain barrier (BBB) is a highly efficient system that separates the central nervous system (CNS) from general circulation and promotes selective transport of molecules that are essential for brain function. However, it also limits the distribution of systemically administered therapeutics to the brain; therefore, there is a restricted number of drugs available for the treatment of brain disorders. Several drug-targeting strategies have been developed to attempt to bypass the BBB, but none has proved sufficiently effective in reaching the brain. The objective of this study is to generally review these strategies of drug administration to the CNS. Noninvasive methods of drug delivery, such as chemical and biologic transport systems, do not represent a feasible platform, whereas for most drugs, it is still not possible to achieve therapeutic levels within the brain tissue after intravenous or oral administration, and the use of higher potency or more concentrated doses may cause serious toxic side effects. Direct intrathecal drug delivery through a catheter into the CNS also presents several problems. Intranasal drug delivery is a potential alternative method due to the direct transport into the cerebrospinal fluid (CSF) compartment along the olfactory pathway, but the study's conclusions are controversial. An endoscopic intranasal surgical procedure using established skull base surgery reconstruction techniques based on the use of a nasal mucosa surgical flap as the only obstacle between the nose and the subarachnoid space has appeared as a potential solution to increase the absorption of intranasal drugs to the CNS. Despite extensive efforts to develop new techniques to cross the BBB, none has proved sufficiently effective in reaching the brain, whereas minimizing adverse effects and the endoscopic mucosal grafting technique offers new potential promise.

  20. Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7.

    PubMed

    van de Wall, Stephanie; Walczak, Mateusz; van Rooij, Nienke; Hoogeboom, Baukje-Nynke; Meijerhof, Tjarko; Nijman, Hans W; Daemen, Toos

    2015-03-24

    The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV) targeting human papillomavirus (HPV). Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7) via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus.

  1. Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7

    PubMed Central

    van de Wall, Stephanie; Walczak, Mateusz; van Rooij, Nienke; Hoogeboom, Baukje-Nynke; Meijerhof, Tjarko; Nijman, Hans W.; Daemen, Toos

    2015-01-01

    The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV) targeting human papillomavirus (HPV). Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7) via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus. PMID:26343186

  2. In elderly persons live attenuated influenza A virus vaccines do not offer an advantage over inactivated virus vaccine in inducing serum or secretory antibodies or local immunologic memory.

    PubMed Central

    Powers, D C; Fries, L F; Murphy, B R; Thumar, B; Clements, M L

    1991-01-01

    In a double-blind, randomized trial, 102 healthy elderly subjects were inoculated with one of four preparations: (i) intranasal bivalent live attenuated influenza vaccine containing cold-adapted A/Kawasaki/86 (H1N1) and cold-adapted A/Bethesda/85 (H3N2) viruses; (ii) parenteral trivalent inactivated subvirion vaccine containing A/Taiwan/86 (H1N1), A/Leningrad/86 (H3N2), and B/Ann Arbor/86 antigens; (iii) both vaccines; or (iv) placebo. To determine whether local or systemic immunization augmented mucosal immunologic memory, all volunteers were challenged intranasally 12 weeks later with the inactivated virus vaccine. We used a hemagglutination inhibition assay to measure antibodies in sera and a kinetic enzyme-linked immunosorbent assay to measure immunoglobulin G (IgG) and IgA antibodies in sera and nasal washes, respectively. In comparison with the live virus vaccine, the inactivated virus vaccine elicited higher and more frequent rises of serum antibodies, while nasal wash antibody responses were similar. The vaccine combination induced serum and local antibodies slightly more often than the inactivated vaccine alone did. Coadministration of live influenza A virus vaccine did not alter the serum antibody response to the influenza B virus component of the inactivated vaccine. The anamnestic nasal antibody response elicited by intranasal inactivated virus challenge did not differ in the live, inactivated, or combined vaccine groups from that observed in the placebo group not previously immunized. These results suggest that in elderly persons cold-adapted influenza A virus vaccines offer little advantage over inactivated virus vaccines in terms of inducing serum or secretory antibody or local immunological memory. Studies are needed to determine whether both vaccines in combination are more efficacious than inactivated vaccine alone in people in this age group. PMID:2037667

  3. Distinct immune responses and virus shedding in pigs following aerosol, intra-nasal and contact infection with pandemic swine influenza A virus, A(H1N1)09.

    PubMed

    Hemmink, Johanneke D; Morgan, Sophie B; Aramouni, Mario; Everett, Helen; Salguero, Francisco J; Canini, Laetitia; Porter, Emily; Chase-Topping, Margo; Beck, Katy; Loughlin, Ronan Mac; Carr, B Veronica; Brown, Ian H; Bailey, Mick; Woolhouse, Mark; Brookes, Sharon M; Charleston, Bryan; Tchilian, Elma

    2016-10-20

    Influenza virus infection in pigs is a major farming problem, causing considerable economic loss and posing a zoonotic threat. In addition the pig is an excellent model for understanding immunity to influenza viruses as this is a natural host pathogen system. Experimentally, influenza virus is delivered to pigs intra-nasally, by intra-tracheal instillation or by aerosol, but there is little data comparing the outcome of different methods. We evaluated the shedding pattern, cytokine responses in nasal swabs and immune responses following delivery of low or high dose swine influenza pdmH1N1 virus to the respiratory tract of pigs intra-nasally or by aerosol and compared them to those induced in naturally infected contact pigs. Our data shows that natural infection by contact induces remarkably high innate and adaptive immune response, although the animals were exposed to a very low virus dose. In contacts, the kinetics of virus shedding were slow and prolonged and more similar to the low dose directly infected animals. In contrast the cytokine profile in nasal swabs, antibody and cellular immune responses of contacts more closely resemble immune responses in high dose directly inoculated animals. Consideration of these differences is important for studies of disease pathogenesis and assessment of vaccine protective efficacy.

  4. Co-delivery of PSA and PSMA DNA vaccines with electroporation induces potent immune responses.

    PubMed

    Ferraro, Bernadette; Cisper, Neil J; Talbott, Kendra T; Philipson-Weiner, Lindsey; Lucke, Colleen E; Khan, Amir S; Sardesai, Niranjan Y; Weiner, David B

    2011-01-01

    Prostate cancer (PCa) remains a significant public health problem. Current treatment modalities for PCa can be useful, but may be accompanied by deleterious side effects and often do not confer long-term control. Accordingly, additional modalities, such as immunotherapy, may represent an important approach for PCa treatment. The identification of tissue-specific antigens engenders PCa an attractive target for immunotherapeutic approaches. Delivery of DNA vaccines with electroporation has shown promising results for prophylactic and therapeutic targets in a variety of species including humans. Application of this technology for PCa immunotherapy strategies has been limited to single antigen and epitope targets. We sought to test the hypothesis that a broader collection of antigens would improve the breadth and effectiveness of a PCa immune therapy approach. We therefore developed highly optimized DNA vaccines encoding prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) as a dual antigen approach to immune therapy of PCa. PSA-and PSMA-specific cellular immunogenicity was evaluated in a mouse model for co-delivery and single antigen vaccination. Mice received 2 immunizations spaced 2 weeks apart and immunogenicity was evaluated 1 week after the second vaccination. Both the PSA and PSMA vaccines induced robust antigen-specific IFNγ responses by ELISpot. Further characterization of cellular immunogenicity by flow cytometry indicated strong antigen-specific TNFα production by CD4+ T cells and IFNγ and IL-2 secretion by both CD4+ and CD8+ T cells. There was also a strong humoral response as determined by PSA-specific seroconversion. These data support further study of this novel approach to immune therapy of PCa.

  5. IgA response and protection following nasal vaccination of chickens with Newcastle disease virus DNA vaccine nanoencapsulated with Ag@SiO2 hollow nanoparticles

    PubMed Central

    Zhao, Kai; Rong, Guangyu; Hao, Yan; Yu, Lu; Kang, Hong; Wang, Xin; Wang, Xiaohua; Jin, Zheng; Ren, Zhiyu; Li, Zejun

    2016-01-01

    Newcastle disease caused by ND virus (NDV) is a highly contagious disease of birds. Vaccine for effective protection of poultry animals from NDV infection is urgently needed. Mucosal immunity plays a very important role in the antiviral immune response. In this study, a NDV F gene-containing DNA vaccine encapsulated in Ag@SiO2 hollow nanoparticles (pFDNA-Ag@SiO2-NPs) with an average diameter of 500 nm were prepared to assess the mucosal immune response. These nanoparticles exhibited low cytotoxicity and did not destroy the bioactivity of plasmid DNA, which could be expressed in vitro. The plasmid DNA was sustainably released after an initial burst release. In vivo immunization showed that the intranasal immunization of chickens with pFDNA-Ag@SiO2-NPs induced high titers of serum antibody, significantly promoted lymphocyte proliferation and induced higher expression levels of IL-2 and IFN-γ in a dose-dependent manner. These results indicated that the Ag@SiO2 hollow nanoparticles could serve as an efficient and safe delivery carrier for NDV DNA vaccine to induce mucosal immunity. This study has provided promising results for the further development of mucosal vaccines encapsulated in inorganic nanoparticles. PMID:27170532

  6. IgA response and protection following nasal vaccination of chickens with Newcastle disease virus DNA vaccine nanoencapsulated with Ag@SiO2 hollow nanoparticles

    NASA Astrophysics Data System (ADS)

    Zhao, Kai; Rong, Guangyu; Hao, Yan; Yu, Lu; Kang, Hong; Wang, Xin; Wang, Xiaohua; Jin, Zheng; Ren, Zhiyu; Li, Zejun

    2016-05-01

    Newcastle disease caused by ND virus (NDV) is a highly contagious disease of birds. Vaccine for effective protection of poultry animals from NDV infection is urgently needed. Mucosal immunity plays a very important role in the antiviral immune response. In this study, a NDV F gene-containing DNA vaccine encapsulated in Ag@SiO2 hollow nanoparticles (pFDNA-Ag@SiO2-NPs) with an average diameter of 500 nm were prepared to assess the mucosal immune response. These nanoparticles exhibited low cytotoxicity and did not destroy the bioactivity of plasmid DNA, which could be expressed in vitro. The plasmid DNA was sustainably released after an initial burst release. In vivo immunization showed that the intranasal immunization of chickens with pFDNA-Ag@SiO2-NPs induced high titers of serum antibody, significantly promoted lymphocyte proliferation and induced higher expression levels of IL-2 and IFN-γ in a dose-dependent manner. These results indicated that the Ag@SiO2 hollow nanoparticles could serve as an efficient and safe delivery carrier for NDV DNA vaccine to induce mucosal immunity. This study has provided promising results for the further development of mucosal vaccines encapsulated in inorganic nanoparticles.

  7. Single-walled carbon nanotubes as delivery vehicles enhance the immunoprotective effects of a recombinant vaccine against Aeromonas hydrophila.

    PubMed

    Gong, Yu-Xin; Zhu, Bin; Liu, Guang-Lu; Liu, Lei; Ling, Fei; Wang, Gao-Xue; Xu, Xin-Gang

    2015-01-01

    To reduce the economic losses caused by diseases in aquaculture industry, more efficient and economic prophylactic measures should be urgently investigated. In this research, the effects of a novel functionalized single-walled carbon nanotubes (SWCNTs) applied as a delivery vehicle for recombinant Aeromonas hydrophila vaccine administration via bath or injection in juvenile grass carp were studied. The results showed that SWCNT as a vector for the recombinant protein aerA, augmented the production of specific antibodies, apparently stimulated the induction of immune-related genes, and induced higher level of survival rate compared with free aerA subunit vaccine. Furthermore, we compared the routes of bath and intramuscular injection immunization by SWCNTs-aerA vaccine, and found that similar antibody levels induced by SWCNTs-aerA were observed in both immunization routes. Meanwhile, a similar relative percentage survival (approximately 80%) was found in both a 40 mg/L bath immunization group, and a 20 μg injection group. The results indicate that functionalized SWCNTs could be a promising delivery vehicle to potentiate the immune response of recombinant vaccines, and might be used to vaccinate juvenile fish by bath administration method. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Effective nonvaccine interventions to be considered alongside human papilloma virus vaccine delivery.

    PubMed

    Hindin, Michelle J; Bloem, Paul; Ferguson, Jane

    2015-01-01

    World Health Organization recommends that girls, ages 9-13 years, get the human papilloma virus (HPV) vaccine. Global Alliance for Vaccines Initiative, which provides low-cost vaccine to eligible countries, requires that an additional intervention to be offered alongside the vaccine. We systematically searched and assessed the published literature in lower- and middle-income countries to identify effective interventions. We conducted systematic searches of four databases: PubMed, EMBASE, Global Index Medicus Regional Databases, and Cochrane Reviews for effective adolescent health interventions that could be delivered with the HPV vaccine in the following areas: (1) iron and folic acid supplementation (iron alone or with folic acid); (2) voucher delivery and cash transfer programs; (3) hand washing and soap provision; (4) vision screening; (5) promotion of physical activity/exercise; (6) menstrual hygiene education; (7) sexual and reproductive health education; (8) human immunodeficiency virus prevention activities; and (9) condom promotion, condom use skill building, and demonstration. We found limited evidence of consistent positive impact. Iron supplementation reduced iron-deficiency anemia and raised serum ferritin levels. Promotion of physical activity lowered blood pressure and reduced weight gain. Sexual and reproductive health and human immunodeficiency virus interventions improved adolescent communication with adults but did not influence behavioral outcomes. Countries should consider locally relevant and proven interventions to be offered alongside the HPV vaccine. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  9. Live RB51 vaccine lyophilized hydrogel formulations with increased shelf life for practical ballistic delivery

    USDA-ARS?s Scientific Manuscript database

    Ballistic delivery capability is essential to delivering vaccines and other therapeutics effectively to both livestock and wildlife in many global scenarios. Here, lyophilized poly(ethylene glycol) (PEG)-glycolide dimethacrylate crosslinked but degradable hydrogels were assessed as payload vehicles ...

  10. New approaches for antigen discovery, production and delivery: vaccines for veterinary and human use.

    PubMed

    Potter, A A; Babiuk, L A

    2001-11-01

    Vaccination of individuals has been practiced for many years and has been one of the most effective methods of controlling infectious diseases. Unfortunately, even with this success, society continues to suffer multi-billion dollar economic losses annually due to infectious diseases. These losses occur in all animal species as well as in humans. In order to further reduce these losses, academicians and companies are employing the multidisciplinary approach to develop better and safer vaccines. These include capitalizing on advances in molecular biology, chemistry, pharmacy, immunology, genomics, proteomics, and fermentation. Thus, we are moving from a more empirical approach to vaccine production to a more focused, and, hopefully, more logical approach to identification and production of protective antigens. Furthermore, formulation and delivery of these antigens in playing a major role in revolutionizing how we deliver vaccines to induce the most appropriate immune response and ensure protection. The current review summarizes some of these advances and speculates as to how future vaccines will be produced and delivered for the benefit of society.

  11. Computed Intranasal Spray Penetration: Comparisons Before and After Nasal Surgery

    PubMed Central

    Frank, Dennis O.; Kimbell, Julia S.; Cannon, Daniel; Rhee, John S.

    2012-01-01

    Background Quantitative methods for comparing intranasal drug delivery efficiencies pre- and postoperatively have not been fully utilized. The objective of this study is to use computational fluid dynamics techniques to evaluate aqueous nasal spray penetration efficiencies before and after surgical correction of intranasal anatomic deformities. Methods Ten three-dimensional models of the nasal cavities were created from pre- and postoperative computed tomography scans in five subjects. Spray simulations were conducted using a particle size distribution ranging from 10–110μm, a spray speed of 3m/s, plume angle of 68°, and with steady state, resting inspiratory airflow present. Two different nozzle positions were compared. Statistical analysis was conducted using Student T-test for matched pairs. Results On the obstructed side, posterior particle deposition after surgery increased by 118% and was statistically significant (p-value=0.036), while anterior particle deposition decreased by 13% and was also statistically significant (p-value=0.020). The fraction of particles that by-passed the airways either pre- or post-operatively was less than 5%. Posterior particle deposition differences between obstructed and contralateral sides of the airways were 113% and 30% for pre- and post-surgery, respectively. Results showed that nozzle positions can influence spray delivery. Conclusions Simulations predicted that surgical correction of nasal anatomic deformities can improve spray penetration to areas where medications can have greater effect. Particle deposition patterns between both sides of the airways are more evenly distributed after surgery. These findings suggest that correcting anatomic deformities may improve intranasal medication delivery. For enhanced particle penetration, patients with nasal deformities may explore different nozzle positions. PMID:22927179

  12. A Review of the Safety, Efficacy and Mechanisms of Delivery of Nasal Oxytocin in Children: Therapeutic Potential for Autism and Prader-Willi Syndrome, and Recommendations for Future Research.

    PubMed

    DeMayo, Marilena M; Song, Yun Ju C; Hickie, Ian B; Guastella, Adam J

    2017-10-01

    In this article, we conduct a comprehensive review of existing evidence for the safety and therapeutic potential of intranasal oxytocin in pediatric populations. Unique considerations for dosing and delivery of oxytocin to the nasal passageway in pediatric populations and methods to promote adherence are reviewed. Intranasal oxytocin has been administered to 261 children in three open-label studies and eight randomized controlled trials. To date, the only published results in pediatric populations have focused on autism spectrum disorder (ASD) and Prader-Willi syndrome (PWS). Results regarding efficacy for improving social impairment in ASD are equivocal, partially due to mixed methodological designs, dosing regimens, and outcome measures. At present, there is no randomized controlled evidence that oxytocin provides benefit to individuals with PWS. There is no clear evidence of a link between oxytocin administration and any specific adverse event. Adverse events have been assessed using medical interviews, open reports, checklists, and physiological assessments. Adverse events reports have been largely classified as mild (n = 93), with few moderate (n = 9) or severe (n = 3) events reported. There were 35 additional adverse events reported, without severity ratings. Severe events, hyperactivity and irritability, occurred at first administration in both placebo and oxytocin groups, and subsided subsequent to discontinuation. We note that adverse event monitoring is inconsistent and often lacking, and reporting of its relationship to the study drug is poor. Only one study reported adherence data to suggest high adherence. Recommendations are then provided for the delivery of nasal sprays to the nasal passageway, monitoring, and reporting of efficacy, safety, and adherence for oxytocin nasal spray trials in pediatric populations.

  13. Novel approaches to vaginal delivery and safety of microbicides: biopharmaceuticals, nanoparticles, and vaccines.

    PubMed

    Whaley, Kevin J; Hanes, Justin; Shattock, Robin; Cone, Richard A; Friend, David R

    2010-12-01

    The HIV-1 epidemic remains unchecked despite existing technology; vaccines and microbicides in development may help reverse the epidemic. Reverse transcriptase inhibitors (RTIs) formulated in gels tenofovir (TFV) and IVRs (dapivirine) are under clinical development. While TFV or similar products may prove successful for HIV-1, alternatives to RTIs may provide additional benefits, e.g., broader STI prevention. Biopharmaceutical agents under development as microbicides include cyanovirin, RANTES analogues, commensals, and Mabs. Cost of manufacturing biopharmaceuticals has been reduced and they can be formulated into tablets, films, and IVRs for vaginal delivery. Nanotechnology offers a novel approach to formulate microbicides potentially leading to uniform epithelial delivery. Delivery through vaginal mucus may be possible by controlling nanoparticle size and surface characteristics. Combining prevention modalities may be the most effective means of preventing STI transmission, importantly, codelivery of microbicides and vaccines has demonstrated. Finally, the safety of microbicide preparations and excipients commonly used can be assessed using a mouse/HSV-2 susceptibility model. Screening of new microbicide candidates and formulation excipients may avoid past issues of enhancing HIV-1 transmission. This article forms part of a special supplement covering several presentations on novel microbicide formulations from the symposium on "Recent Trends in Microbicide Formulations" held on 25 and 26 January 2010, Arlington, VA. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. European union regulatory developments for new vaccine adjuvants and delivery systems.

    PubMed

    Sesardic, Dorothea; Dobbelaer, Roland

    2004-06-23

    Interest in vaccine adjuvants and new delivery systems has grown rapidly over the past few years. New vaccine candidates have emerged, which, because of their poor immunogenicity, rely on adjuvants to improve their presentation and targeting and to potentiate their protective immune response. Better understandings of the mechanisms of action, together with logistic and economical considerations have resulted in an explosion of technologies. However, there have been few new registered products for human use, and antigens incorporated into immunostimulating reconstituted influenza virosomes have only relatively recently been licensed in European Union (EU) countries. Influenza vaccine, adjuvanted with water in oil emulsion containing squalene (adjuvant MF59C1) is now also approved. Although current EU regulations focus on traditional adjuvants, notably aluminium and calcium salts, advances have been made in regulatory considerations. The European agency for the evaluation of medicinal products, through its working parties, is actively drafting guidance on requirements for the evaluation of new adjuvants in vaccines. This paper summarises the new developments in EU regulatory aspects relevant to adjuvant quality at development stages, during the manufacturing process, and at the final bulk stage of adjuvant with antigen, and also summarises regulatory expectation regarding safety at pre-clinical and clinical stages. The paper highlights the regulatory concerns and existing bottlenecks that have led to slow approval of new technologies.

  15. Tulane/Xavier Vaccine Peptide Program

    DTIC Science & Technology

    2013-07-01

    include a dry powder formulation, microemulsions , nonspherical liposomes, ceramic shell vesicles, and nanometer-sized silk particles. Nasal...pulmonary delivery: dry powder formulation, microemulsions , nonspherical liposomes, ceramic shell vesicles, and nanometer-sized silk particles. (3) Confirm...include a dry powder formulation, microemulsions , nonspherical liposomes, ceramic shell vesicles, and nanometer-sized silk particles. Nasal

  16. Antigen-displaying lipid-enveloped PLGA nanoparticles as delivery agents for a Plasmodium vivax malaria vaccine.

    PubMed

    Moon, James J; Suh, Heikyung; Polhemus, Mark E; Ockenhouse, Christian F; Yadava, Anjali; Irvine, Darrell J

    2012-01-01

    The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide) acid (PLGA) "enveloped" by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA), was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs). Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites.

  17. Newcastle disease virus vectored vaccines as bivalent or antigen delivery vaccines

    PubMed Central

    2017-01-01

    Recent advances in reverse genetics techniques make it possible to manipulate the genome of RNA viruses such as Newcastle disease virus (NDV). Several NDV vaccine strains have been used as vaccine vectors in poultry, mammals, and humans to express antigens of different pathogens. The safety, immunogenicity, and protective efficacy of these NDV-vectored vaccines have been evaluated in pre-clinical and clinical studies. The vaccines are safe in mammals, humans, and poultry. Bivalent NDV-vectored vaccines against pathogens of economic importance to the poultry industry have been developed. These bivalent vaccines confer solid protective immunity against NDV and other foreign antigens. In most cases, NDV-vectored vaccines induce strong local and systemic immune responses against the target foreign antigen. This review summarizes the development of NDV-vectored vaccines and their potential use as a base for designing other effective vaccines for veterinary and human use. PMID:28775971

  18. Detection of influenza A virus in aerosols of vaccinated and non-vaccinated pigs in a warm environment.

    PubMed

    Neira, Victor; Allerson, Matt; Corzo, Cesar; Culhane, Marie; Rendahl, Aaron; Torremorell, Montserrat

    2018-01-01

    The 2009 influenza pandemic, the variant H3N2v viruses in agricultural fairs and the zoonotic poultry H5N9 infections in China have highlighted the constant threat that influenza A viruses (IAV) present to people and animals. In this study we evaluated the effect of IAV vaccination on aerosol shedding in pigs housed in warm environmental conditions. Thirty-six, three-week old weaned pigs were obtained from an IAV negative herd and were randomly allocated to one of 4 groups: 1) a homologous vaccine group, 2) a heterologous multivalent vaccine group, 3) a heterologous monovalent group and, 4) a non-vaccinated group. After vaccination pigs were challenged with the triple reassortant A/Sw/IA/00239/04 H1N1 virus. Environmental temperature and relative humidity were recorded throughout the study. Nasal swabs, oral fluids and air samples were collected daily. All samples were tested by RRT-PCR and virus isolation was attempted on positive samples. Average temperature and relative humidity throughout the study were 27°C (80°F) and 53%, respectively. A significantly higher proportion of infected pigs was detected in the non-vaccinated than in the vaccinated group. Lower levels of nasal virus shedding were found in vaccinated groups compared to non-vaccinated group and IAV was not detected in air samples of any of the vaccinated groups. In contrast, positive air samples were detected in the non-vaccinated group at 1, 2 and 3 days post infection although the overall levels were considered low most likely due to the elevated environmental temperature. In conclusion, both the decrease in shedding and the increase in environmental temperature may have contributed to the inability to detect airborne IAV in vaccinated pigs.

  19. Induction of CD8(+) T cell responses and protective efficacy following microneedle-mediated delivery of a live adenovirus-vectored malaria vaccine.

    PubMed

    Pearson, Frances E; O'Mahony, Conor; Moore, Anne C; Hill, Adrian V S

    2015-06-22

    There is an urgent need for improvements in vaccine delivery technologies. This is particularly pertinent for vaccination programmes within regions of limited resources, such as those required for adequate provision for disposal of used needles. Microneedles are micron-sized structures that penetrate the stratum corneum of the skin, creating temporary conduits for the needle-free delivery of drugs or vaccines. Here, we aimed to investigate immunity induced by the recombinant simian adenovirus-vectored vaccine ChAd63.ME-TRAP; currently undergoing clinical assessment as a candidate malaria vaccine, when delivered percutaneously by silicon microneedle arrays. In mice, we demonstrate that microneedle-mediated delivery of ChAd63.ME-TRAP induced similar numbers of transgene-specific CD8(+) T cells compared to intradermal (ID) administration with needle-and-syringe, following a single immunisation and after a ChAd63/MVA heterologous prime-boost schedule. When mice immunised with ChAd63/MVA were challenged with live Plasmodium berghei sporozoites, microneedle-mediated ChAd63.ME-TRAP priming demonstrated equivalent protective efficacy as did ID immunisation. Furthermore, responses following ChAd63/MVA immunisation correlated with a specific design parameter of the array used ('total array volume'). The level of transgene expression at the immunisation site and skin-draining lymph node (dLN) was also linked to total array volume. These findings have implications for defining silicon microneedle array design for use with live, vectored vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Biodegradable nanoparticle delivery of inactivated swine influenza virus vaccine provides heterologous cell-mediated immune response in pigs.

    PubMed

    Dhakal, Santosh; Hiremath, Jagadish; Bondra, Kathryn; Lakshmanappa, Yashavanth S; Shyu, Duan-Liang; Ouyang, Kang; Kang, Kyung-Il; Binjawadagi, Basavaraj; Goodman, Jonathan; Tabynov, Kairat; Krakowka, Steven; Narasimhan, Balaji; Lee, Chang Won; Renukaradhya, Gourapura J

    2017-02-10

    Swine influenza virus (SwIV) is one of the important zoonotic pathogens. Current flu vaccines have failed to provide cross-protection against evolving viruses in the field. Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable FDA approved polymer and widely used in drug and vaccine delivery. In this study, inactivated SwIV H1N2 antigens (KAg) encapsulated in PLGA nanoparticles (PLGA-KAg) were prepared, which were spherical in shape with 200 to 300nm diameter, and induced maturation of antigen presenting cells in vitro. Pigs vaccinated twice with PLGA-KAg via intranasal route showed increased antigen specific lymphocyte proliferation and enhanced the frequency of T-helper/memory and cytotoxic T cells (CTLs) in peripheral blood mononuclear cells (PBMCs). In PLGA-KAg vaccinated and heterologous SwIV H1N1 challenged pigs, clinical flu symptoms were absent, while the control pigs had fever for four days. Grossly and microscopically, reduced lung pathology and viral antigenic mass in the lung sections with clearance of infectious challenge virus in most of the PLGA-KAg vaccinated pig lung airways were observed. Immunologically, PLGA-KAg vaccine irrespective of not significantly boosting the mucosal antibody response, it augmented the frequency of IFN-γ secreting total T cells, T-helper and CTLs against both H1N2 and H1N1 SwIV. In summary, inactivated influenza virus delivered through PLGA-NPs reduced the clinical disease and induced cross-protective cell-mediated immune response in a pig model. Our data confirmed the utility of a pig model for intranasal particulate flu vaccine delivery platform to control flu in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. In vitro evaluation of radio-labeled aerosol delivery via a variable-flow infant CPAP system.

    PubMed

    Farney, Kimberly D; Kuehne, Brandon T; Gibson, Laurie A; Nelin, Leif D; Shepherd, Edward G

    2014-03-01

    Nasal CPAP is widely used in neonatal ICUs. Aerosolized medications such as inhaled steroids and β agonists are commonly administered in-line through nasal CPAP, especially to infants with bronchopulmonary dysplasia. We hypothesized that aerosol delivery to the lungs via variable-flow nasal CPAP in an in vitro model would be unreliable, and that the delivery would depend on the position of the aerosol generator within the nasal CPAP circuit. We used a system that employed a test lung placed in a plastic jar and subjected to negative pressure. Simulated inspiration effort was measured with a heated-wire anemometer. We used technetium-99m-labeled diethylene triamine penta-acetic acid as our aerosol. The nebulizer was placed either close to the humidifier or close to the nasal prongs in the circuit, and patient effort was simulated with a minute ventilation of 0.4 L/min. Relative aerosol delivery to the infant test lung with the nebulizer close to the humidifier was extremely low (0.3 ± 0.4%), whereas placing the nebulizer close to the nasal prongs resulted in significantly (P < .001) improved delivery (21 ± 11%). Major areas of aerosol deposition with the nebulizer close to the humidifier versus close to the nasal prongs were: nebulizer (10 ± 4% vs 33 ± 13%, P < .001), exhalation limb (9 ± 17% vs 26 ± 30%, P = .23), and generator tubing (21 ± 11% vs 19 ± 20%, P = .86). Placing the nebulizer close to the humidifier resulted in 59 ± 8% of the aerosol being deposited in the inhalation tubing along the heater wire. Isotope delivery from an aerosol generator placed near the humidifier on variable-flow nasal CPAP was negligible in this in vitro setup; however, such delivery was significantly improved by locating the aerosol generator closer to the nasal CPAP interface.

  2. Clinical evaluation of a novel microneedle device for intradermal delivery of an influenza vaccine: are all delivery methods the same?

    PubMed

    Levin, Yotam; Kochba, Efrat; Kenney, Richard

    2014-07-23

    The skin provides the largest immune barrier to infection and is a readily accessible site for vaccination, although intradermal (ID) injection can be challenging. The MicronJet™ microneedle is a novel device that consistently injects antigens very close to the skin's dendritic cells. A dose-sparing ID injection study was conducted in 280 healthy adult volunteers using trivalent virosomal adjuvanted influenza vaccine. ID injection of 3 μg using the MicronJet™ was well tolerated and showed a statistically higher geometric mean fold rise than the same dose ID using a conventional needle (Mantoux technique) for the H1N1 and B strains or a 15 μg intramuscular (IM) injection for the H3N2 strain. Thus, the immune response appears to partially depend on the delivery device and route of injection. The MicronJet™ may allow dose-sparing, yet give a superior response in influenza vaccination and warrants further clinical evaluation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. A case study using the United Republic of Tanzania: costing nationwide HPV vaccine delivery using the WHO Cervical Cancer Prevention and Control Costing Tool.

    PubMed

    Hutubessy, Raymond; Levin, Ann; Wang, Susan; Morgan, Winthrop; Ally, Mariam; John, Theopista; Broutet, Nathalie

    2012-11-13

    The purpose, methods, data sources and assumptions behind the World Health Organization (WHO) Cervical Cancer Prevention and Control Costing (C4P) tool that was developed to assist low- and middle-income countries (LMICs) with planning and costing their nationwide human papillomavirus (HPV) vaccination program are presented. Tanzania is presented as a case study where the WHO C4P tool was used to cost and plan the roll-out of HPV vaccines nationwide as part of the national comprehensive cervical cancer prevention and control strategy. The WHO C4P tool focuses on estimating the incremental costs to the health system of vaccinating adolescent girls through school-, health facility- and/or outreach-based strategies. No costs to the user (school girls, parents or caregivers) are included. Both financial (or costs to the Ministry of Health) and economic costs are estimated. The cost components for service delivery include training, vaccination (health personnel time and transport, stationery for tally sheets and vaccination cards, and so on), social mobilization/IEC (information, education and communication), supervision, and monitoring and evaluation (M&E). The costs of all the resources used for HPV vaccination are totaled and shown with and without the estimated cost of the vaccine. The total cost is also divided by the number of doses administered and number of fully immunized girls (FIGs) to estimate the cost per dose and cost per FIG. Over five years (2011 to 2015), the cost of establishing an HPV vaccine program that delivers three doses of vaccine to girls at schools via phased national introduction (three regions in year 1, ten regions in year 2 and all 26 regions in years 3 to 5) in Tanzania is estimated to be US$9.2 million (excluding vaccine costs) and US$31.5 million (with vaccine) assuming a vaccine price of US$5 (GAVI 2011, formerly the Global Alliance for Vaccines and Immunizations). This is equivalent to a financial cost of US$5.77 per FIG, excluding

  4. A case study using the United Republic of Tanzania: costing nationwide HPV vaccine delivery using the WHO Cervical Cancer Prevention and Control Costing Tool

    PubMed Central

    2012-01-01

    Background The purpose, methods, data sources and assumptions behind the World Health Organization (WHO) Cervical Cancer Prevention and Control Costing (C4P) tool that was developed to assist low- and middle-income countries (LMICs) with planning and costing their nationwide human papillomavirus (HPV) vaccination program are presented. Tanzania is presented as a case study where the WHO C4P tool was used to cost and plan the roll-out of HPV vaccines nationwide as part of the national comprehensive cervical cancer prevention and control strategy. Methods The WHO C4P tool focuses on estimating the incremental costs to the health system of vaccinating adolescent girls through school-, health facility- and/or outreach-based strategies. No costs to the user (school girls, parents or caregivers) are included. Both financial (or costs to the Ministry of Health) and economic costs are estimated. The cost components for service delivery include training, vaccination (health personnel time and transport, stationery for tally sheets and vaccination cards, and so on), social mobilization/IEC (information, education and communication), supervision, and monitoring and evaluation (M&E). The costs of all the resources used for HPV vaccination are totaled and shown with and without the estimated cost of the vaccine. The total cost is also divided by the number of doses administered and number of fully immunized girls (FIGs) to estimate the cost per dose and cost per FIG. Results Over five years (2011 to 2015), the cost of establishing an HPV vaccine program that delivers three doses of vaccine to girls at schools via phased national introduction (three regions in year 1, ten regions in year 2 and all 26 regions in years 3 to 5) in Tanzania is estimated to be US$9.2 million (excluding vaccine costs) and US$31.5 million (with vaccine) assuming a vaccine price of US$5 (GAVI 2011, formerly the Global Alliance for Vaccines and Immunizations). This is equivalent to a financial cost of US

  5. The golden ratio of nasal width to nasal bone length.

    PubMed

    Goynumer, G; Yayla, M; Durukan, B; Wetherilt, L

    2011-01-01

    To calculate the ratio of fetal nasal width over nasal bone length at 14-39 weeks' gestation in Caucasian women. Fetal nasal bone length and nasal width at 14-39 weeks' gestation were measured in 532 normal fetuses. The mean and standard deviations of fetal nasal bone length, nasal width and their ratio to one another were calculated in normal fetuses according to the gestational age to establish normal values. A positive and linear correlation was detected between the nasal bone length and the gestational week, as between the nasal width and the gestational week. No linear growth pattern was found between the gestational week and the ratio of nasal width to nasal bone length, nearly equal to phi, throughout gestation. The ratio of nasal width to nasal bone length, approximately equal to phi, can be calculated at 14-38 weeks' gestation. This might be useful in evaluating fetal abnormalities.

  6. Gold nanocluster-based vaccines for dual-delivery of antigens and immunostimulatory oligonucleotides

    NASA Astrophysics Data System (ADS)

    Tao, Yu; Zhang, Yan; Ju, Enguo; Ren, Hui; Ren, Jinsong

    2015-07-01

    We here report a facile one-pot synthesis of fluorescent gold nanoclusters (AuNCs) via the peptide biomineralization method, which can elicit specific immunological responses. The as-prepared peptide-protected AuNCs (peptide-AuNCs) display strong red fluorescence, and more importantly, as compared to the peptide alone, the immune stimulatory ability of the resulting peptide-AuNCs can not only be retained, but can also be efficaciously enhanced. Moreover, through a dual-delivery of antigen peptides and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs), the as-prepared peptide-AuNC-CpG conjugates can also act as smart self-vaccines to assist in the generation of high immunostimulatory activity, and be applied as a probe for intracellular imaging. Both in vitro and in vivo studies provide strong evidence that the AuNC-based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments.We here report a facile one-pot synthesis of fluorescent gold nanoclusters (AuNCs) via the peptide biomineralization method, which can elicit specific immunological responses. The as-prepared peptide-protected AuNCs (peptide-AuNCs) display strong red fluorescence, and more importantly, as compared to the peptide alone, the immune stimulatory ability of the resulting peptide-AuNCs can not only be retained, but can also be efficaciously enhanced. Moreover, through a dual-delivery of antigen peptides and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs), the as-prepared peptide-AuNC-CpG conjugates can also act as smart self-vaccines to assist in the generation of high immunostimulatory activity, and be applied as a probe for intracellular imaging. Both in vitro and in vivo studies provide strong evidence that the AuNC-based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments. Electronic supplementary information (ESI

  7. Antigen discovery and delivery of subunit vaccines by nonliving bacterial ghost vectors.

    PubMed

    Walcher, Petra; Mayr, Ulrike B; Azimpour-Tabrizi, Chakameh; Eko, Francis O; Jechlinger, Wolfgang; Mayrhofer, Peter; Alefantis, Tim; Mujer, Cesar V; DelVecchio, Vito G; Lubitz, Werner

    2004-12-01

    The bacterial ghost (BG) platform system is a novel vaccine delivery system endowed with intrinsic adjuvant properties. BGs are nonliving Gram-negative bacterial cell envelopes which are devoid of their cytoplasmic contents, yet maintain their cellular morphology and antigenic structures, including bioadhesive properties. The main advantages of BGs as carriers of subunit vaccines include their ability to stimulate a high immune response and to target the carrier itself to primary antigen-presenting cells. The intrinsic adjuvant properties of BGs enhance the immune response to target antigens, including T-cell activation and mucosal immunity. Since native and foreign antigens can be carried in the envelope complex of BGs, combination vaccines with multiple antigens of diverse origin can be presented to the immune system simultaneously. Beside the capacity of BGs to function as carriers of protein antigens, they also have a high loading capacity for DNA. Thus, loading BGs with recombinant DNA takes advantage of the excellent bioavailability for DNA-based vaccines and the high expression rates of the DNA-encoded antigens in target cell types such as macrophages and dendritic cells. There are many spaces within BGs including the inner and outer membranes, the periplasmic space and the internal lumen which can carry antigens, DNA or mediators of the immune response. All can be used for subunit antigen to design new vaccine candidates with particle presentation technology. In addition, the fact that BGs can also carry piggyback large-size foreign antigen particles, increases the technologic usefulness of BGs as combination vaccines against viral and bacterial pathogens. Furthermore, the BG antigen carriers can be stored as freeze-dried preparations at room temperature for extended periods without loss of efficacy. The potency, safety and relatively low production cost of BGs offer a significant technical advantage over currently utilized vaccine technologies.

  8. Nasal polyps

    MedlinePlus

    ... get rid of nasal polyps. Nasal steroid sprays shrink polyps. They help clear blocked nasal passages and ... is stopped. Corticosteroid pills or liquid may also shrink polyps, and can reduce swelling and nasal congestion. ...

  9. Transport networks and inequities in vaccination: remoteness shapes measles vaccine coverage and prospects for elimination across Africa.

    PubMed

    Metcalf, C J E; Tatem, A; Bjornstad, O N; Lessler, J; O'Reilly, K; Takahashi, S; Cutts, F; Grenfell, B T

    2015-05-01

    Measles vaccination is estimated to have averted 13·8 million deaths between 2000 and 2012. Persisting heterogeneity in coverage is a major contributor to continued measles mortality, and a barrier to measles elimination and introduction of rubella-containing vaccine. Our objective is to identify determinants of inequities in coverage, and how vaccine delivery must change to achieve elimination goals, which is a focus of the WHO Decade of Vaccines. We combined estimates of travel time to the nearest urban centre (⩾50 000 people) with vaccination data from Demographic Health Surveys to assess how remoteness affects coverage in 26 African countries. Building on a statistical mapping of coverage against age and geographical isolation, we quantified how modifying the rate and age range of vaccine delivery affects national coverage. Our scenario analysis considers increasing the rate of delivery of routine vaccination, increasing the target age range of routine vaccination, and enhanced delivery to remote areas. Geographical isolation plays a key role in defining vaccine inequity, with greater inequity in countries with lower measles vaccine coverage. Eliminating geographical inequities alone will not achieve thresholds for herd immunity, indicating that changes in delivery rate or age range of routine vaccination will be required. Measles vaccine coverage remains far below targets for herd immunity in many countries on the African continent and is likely to be inadequate for achieving rubella elimination. The impact of strategies such as increasing the upper age range eligible for routine vaccination should be considered.

  10. Effects of Bifidobacterium Breve Feeding Strategy and Delivery Modes on Experimental Allergic Rhinitis Mice.

    PubMed

    Ren, Jian-jun; Yu, Zhao; Yang, Feng-Ling; Lv, Dan; Hung, Shi; Zhang, Jie; Lin, Ping; Liu, Shi-Xi; Zhang, Nan; Bachert, Claus

    2015-01-01

    Different delivery modes may affect the susceptibility to allergic diseases. It is still unknown whether early intervention with probiotics would counteract this effect. The effect of different delivery modes on immune status and nasal symptoms was investigated on established allergic rhinitis (AR) mouse model. In addition, the immunoregulatory effects and mechanisms of different feeding manners with Bifidobacterium breve(B. breve) were examined. Live lyophilized B. breve was orally administered to BALB/c mice born via vaginal delivery(VD) or cesarean delivery (CD) for 8 consecutive weeks, after which they were sensitized by ovalbumin(OVA) to establish experimental AR. Nasal symptoms, serum immunoglobulins, cytokines, splenic percentages of CD4(+)CD25(+)Foxp3(+) regulatory T(Treg) cells and nasal eosinophil infiltration were evaluated. Compared with VD mice, mice delivered via CD demonstrated more serious nasal symptoms, higher concentrations of OVA-specific immunoglobulin (Ig) E, more nasal eosinophils and lower percentages of splenic CD4(+)CD25(+)Foxp3(+)Treg cells after establishing experimental AR. These parameters were reversed by administering B. breves hortly after birth. However, the effect of B. breve did not differ between different delivery modes. CD aggravates the nasal symptoms of AR mice compared to VD. This is the first report that oral administration of B. breve shortly after birth can significantly alleviate the symptoms of AR mice born via both deliveries, probably via activation of the regulatory capacity of CD4(+)CD25(+)Foxp3(+)Treg cells.

  11. Comparison of Nasal Acceleration and Nasalance across Vowels

    ERIC Educational Resources Information Center

    Thorp, Elias B.; Virnik, Boris T.; Stepp, Cara E.

    2013-01-01

    Purpose: The purpose of this study was to determine the performance of normalized nasal acceleration (NNA) relative to nasalance as estimates of nasalized versus nonnasalized vowel and sentence productions. Method: Participants were 18 healthy speakers of American English. NNA was measured using a custom sensor, and nasalance was measured using…

  12. Evaluation of biocompatibility and administration site reactogenicity of polyanhydride-particle-based platform for vaccine delivery.

    PubMed

    Huntimer, Lucas; Ramer-Tait, Amanda E; Petersen, Latrisha K; Ross, Kathleen A; Walz, Katherine A; Wang, Chong; Hostetter, Jesse; Narasimhan, Balaji; Wannemuehler, Michael J

    2013-02-01

    Efficacy, purity, safety, and potency are important attributes of vaccines. Polyanhydride particles represent a novel class of vaccine adjuvants and delivery platforms that have demonstrated the ability to enhance the stability of protein antigens as well as elicit protective immunity against bacterial pathogens. This work aims to elucidate the biocompatibility, inflammatory reactions, and particle effects on mice injected with a 5 mg dose of polyanhydride nanoparticles via common parenteral routes (subcutaneous and intramuscular). Independent of polymer chemistry, nanoparticles more effectively disseminated away from the injection site as compared to microparticles, which exhibited a depot effect. Using fluorescent probes, the in vivo distribution of three formulations of nanoparticles, following subcutaneous administration, indicated migration away from the injection site. Less inflammation was observed at the injection sites of mice-administered nanoparticles as compared to Alum and incomplete Freund's adjuvant. Furthermore, histological evaluation revealed minimal adverse injection site reactions and minimal toxicological effects associated with the administration of nanoparticles at 30 days post-administration. Collectively, these results demonstrate that polyanhydride nanoparticles do not induce inflammation as a cumulative effect of particle persistence or degradation and are, therefore, a viable candidate for a vaccine delivery platform. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Plasmid DNA loaded chitosan nanoparticles for nasal mucosal immunization against hepatitis B.

    PubMed

    Khatri, Kapil; Goyal, Amit K; Gupta, Prem N; Mishra, Neeraj; Vyas, Suresh P

    2008-04-16

    This work investigates the preparation and in vivo efficacy of plasmid DNA loaded chitosan nanoparticles for nasal mucosal immunization against hepatitis B. Chitosan pDNA nanoparticles were prepared using a complex coacervation process. Prepared nanoparticles were characterized for size, shape, surface charge, plasmid loading and ability of nanoparticles to protect DNA against nuclease digestion and for their transfection efficacy. Nasal administration of nanoparticles resulted in serum anti-HBsAg titre that was less compared to that elicited by naked DNA and alum adsorbed HBsAg, but the mice were seroprotective within 2 weeks and the immunoglobulin level was above the clinically protective level. However, intramuscular administration of naked DNA and alum adsorbed HBsAg did not elicit sIgA titre in mucosal secretions that was induced by nasal immunization with chitosan nanoparticles. Similarly, cellular responses (cytokine levels) were poor in case of alum adsorbed HBsAg. Chitosan nanoparticles thus produced humoral (both systemic and mucosal) and cellular immune responses upon nasal administration. The study signifies the potential of chitosan nanoparticles as DNA vaccine carrier and adjuvant for effective immunization through non-invasive nasal route.

  14. Nasal deposition of ciclesonide nasal aerosol and mometasone aqueous nasal spray in allergic rhinitis patients.

    PubMed

    Emanuel, Ivor A; Blaiss, Michael S; Meltzer, Eli O; Evans, Philip; Connor, Alyson

    2014-01-01

    Sensory attributes of intranasal corticosteroids, such as rundown to the back of the throat, may influence patient treatment preferences. This study compares the nasal deposition and nasal retention of a radiolabeled solution of ciclesonide nasal aerosol (CIC-hydrofluoroalkane [HFA]) with a radiolabeled suspension of mometasone furoate monohydrate aqueous nasal spray (MFNS) in subjects with either perennial allergic rhinitis (AR) or seasonal AR. In this open-label, single-dose, randomized, crossover scintigraphy study, 14 subjects with symptomatic AR received a single dose of radiolabeled 74-μg CIC-HFA (37 μg/spray, 1 spray/each nostril) via a nasal metered-dose inhaler or a single dose of radiolabeled 200-μg MFNS (50 μg/spray, 2 sprays/each nostril), with a minimum 5-day washout period between treatments. Initial deposition (2 minutes postdose) of radiolabeled CIC-HFA and MFNS in the nasal cavity, nasopharynx, and on nasal wipes, and retention of radioactivity in the nasal cavity and nasal run-out on nasal wipes at 2, 4, 6, 8, and 10 minutes postdose were quantified with scintigraphy. At 2 and 10 minutes postdose, deposition of radiolabeled CIC-HFA was significantly higher in the nasal cavity versus radiolabeled MFNS (99.42% versus 86.50% at 2 minutes, p = 0.0046; and 81.10% versus 54.31% at 10 minutes, p < 0.0001, respectively; p values unadjusted for multiplicity). Deposition of radioactivity on nasal wipes was significantly higher with MFNS versus CIC-HFA at all five time points, and posterior losses of radiolabeled formulation were significantly higher with MFNS at 6, 8, and 10 minutes postdose. In this scintigraphic study, significantly higher nasal deposition and retention of radiolabeled aerosol CIC-HFA were observed versus radiolabeled aqueous MFNS in subjects with AR.

  15. Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus

    PubMed Central

    Morgan, Sophie B.; Hemmink, Johanneke D.; Porter, Emily; Harley, Ross; Shelton, Holly; Aramouni, Mario; Everett, Helen E.; Brookes, Sharon M.; Bailey, Michael; Townsend, Alain M.; Charleston, Bryan

    2016-01-01

    Influenza A viruses are a major health threat to livestock and humans, causing considerable mortality, morbidity, and economic loss. Current inactivated influenza vaccines are strain specific and new vaccines need to be produced at frequent intervals to combat newly arising influenza virus strains, so that a universal vaccine is highly desirable. We show that pandemic H1N1 influenza virus in which the hemagglutinin signal sequence has been suppressed (S-FLU), when administered to pigs by aerosol can induce CD4 and CD8 T cell immune responses in blood, bronchoalveolar lavage (BAL), and tracheobronchial lymph nodes. Neutralizing Ab was not produced. Detection of a BAL response correlated with a reduction in viral titer in nasal swabs and lungs, following challenge with H1N1 pandemic virus. Intratracheal immunization with a higher dose of a heterologous H5N1 S-FLU vaccine induced weaker BAL and stronger tracheobronchial lymph node responses and a lesser reduction in viral titer. We conclude that local cellular immune responses are important for protection against influenza A virus infection, that these can be most efficiently induced by aerosol immunization targeting the lower respiratory tract, and that S-FLU is a promising universal influenza vaccine candidate. PMID:27183611

  16. Nasal immunization with M cell-targeting ligand-conjugated ApxIIA toxin fragment induces protective immunity against Actinobacillus pleuropneumoniae infection in a murine model.

    PubMed

    Park, Jisang; Seo, Ki-Weon; Kim, Sae-Hae; Lee, Ha-Yan; Kim, Bumseok; Lim, Chae Woong; Kim, Jin-Hee; Yoo, Han Sang; Jang, Yong-Suk

    2015-05-15

    Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia and severe economic loss in the swine industry has been caused by the infection. Therefore, the development of an effective vaccine against the bacteria is necessary. ApxII toxin, among several virulence factors expressed by the bacteria, is considered to be a promising vaccine candidate because ApxII toxin not only accompanies cytotoxic and hemolytic activities, but is also expressed in all 15 serotypes of bacteria except serotypes 10 and 14. In this study, we identified the peptide ligand capable of targeting the ligand-conjugated ApxIIA #5 fragment antigen to nasopharynx-associated lymphoid tissue. It was found that nasal immunization with ligand-conjugated ApxIIA #5 induced efficient mucosal and systemic immune responses measured at the levels of antigen-specific antibodies, cytokine-secreting cells after antigen exposure, and antigen-specific lymphocyte proliferation. More importantly, the nasal immunization induced protective immunity against nasal challenge infection of the bacteria, which was confirmed by histopathological studies and bacterial clearance after challenge infection. Collectively, we confirmed that the ligand capable of targeting the ligand-conjugated antigen to nasopharynx-associated lymphoid tissue can be used as an effective nasal vaccine adjuvant to induce protective immunity against A. pleuropneumoniae infection. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Physician Knowledge and Attitudes About Hepatitis A and Current Practices Regarding Hepatitis A Vaccination Delivery.

    PubMed

    Nelson, Noele P; Allison, Mandy A; Lindley, Megan C; Brtnikova, Michaela; Crane, Lori A; Beaty, Brenda L; Hurley, Laura P; Kempe, Allison

    2017-07-01

    To assess physicians': 1) knowledge and attitudes about hepatitis A disease and hepatitis A (HepA) vaccine, 2) child care and school HepA vaccine mandates, 3) practices related to HepA vaccine delivery, 4) factors associated with strongly recommending HepA vaccine to all 1- to 2-year-olds, and 5) feasibility of implementing HepA catch-up vaccination at health maintenance visits. A national survey was conducted among representative networks of pediatricians and family medicine physicians (FMs) from March to June, 2014 via e-mail or mail on the basis of provider preference. Response rates were 81% (356 of 440) among pediatricians and 75% (348 of 464) among FMs. Less than 50% correctly identified that hepatitis A virus (HAV) infection is usually asymptomatic in young children and that morbidity from HAV disease increases with age. Ninety-two percent of pediatricians and 59% of FMs strongly recommend HepA vaccine for all 1- to 2-year-olds. In addition to practice specialty, belief that HepA vaccine is required for kindergarten enrollment was the most robust predictor of strong physician recommendation. Gaps in knowledge regarding HAV infection and hepatitis A recommendations and lack of a strong recommendation for routine HepA vaccination of young children among FMs likely contribute to suboptimal coverage. Closing knowledge gaps and addressing barriers that prevent all physicians from strongly recommending HepA vaccine to 1- to 2-year-olds could help increase HepA vaccine coverage and ultimately improve population protection against HAV infection. Published by Elsevier Inc.

  18. Applying Genomic and Bioinformatic Resources to Human Adenovirus Genomes for Use in Vaccine Development and for Applications in Vector Development for Gene Delivery

    PubMed Central

    Seto, Jason; Walsh, Michael P.; Mahadevan, Padmanabhan; Zhang, Qiwei; Seto, Donald

    2010-01-01

    Technological advances and increasingly cost-effect methodologies in DNA sequencing and computational analysis are providing genome and proteome data for human adenovirus research. Applying these tools, data and derived knowledge to the development of vaccines against these pathogens will provide effective prophylactics. The same data and approaches can be applied to vector development for gene delivery in gene therapy and vaccine delivery protocols. Examination of several field strain genomes and their analyses provide examples of data that are available using these approaches. An example of the development of HAdV-B3 both as a vaccine and also as a vector is presented. PMID:21994597

  19. Combinatorial evaluation of in vivo distribution of polyanhydride particle-based platforms for vaccine delivery

    PubMed Central

    Petersen, Latrisha K; Huntimer, Lucas; Walz, Katharine; Ramer-Tait, Amanda; Wannemuehler, Michael J; Narasimhan, Balaji

    2013-01-01

    Several challenges are associated with current vaccine strategies, including repeated immunizations, poor patient compliance, and limited approved routes for delivery, which may hinder induction of protective immunity. Thus, there is a need for new vaccine adjuvants capable of multi-route administration and prolonged antigen release at the site of administration by providing a depot within tissue. In this work, we designed a combinatorial platform to investigate the in vivo distribution, depot effect, and localized persistence of polyanhydride nanoparticles as a function of nanoparticle chemistry and administration route. Our observations indicated that the route of administration differentially affected tissue residence times. All nanoparticles rapidly dispersed when delivered intranasally but provided a depot when administered parenterally. When amphiphilic and hydrophobic nanoparticles were administered intranasally, they persisted within lung tissue. These results provide insights into the chemistry- and route-dependent distribution and tissue-specific association of polyanhydride nanoparticle-based vaccine adjuvants. PMID:23818778

  20. Combinatorial evaluation of in vivo distribution of polyanhydride particle-based platforms for vaccine delivery.

    PubMed

    Petersen, Latrisha K; Huntimer, Lucas; Walz, Katharine; Ramer-Tait, Amanda; Wannemuehler, Michael J; Narasimhan, Balaji

    2013-01-01

    Several challenges are associated with current vaccine strategies, including repeated immunizations, poor patient compliance, and limited approved routes for delivery, which may hinder induction of protective immunity. Thus, there is a need for new vaccine adjuvants capable of multi-route administration and prolonged antigen release at the site of administration by providing a depot within tissue. In this work, we designed a combinatorial platform to investigate the in vivo distribution, depot effect, and localized persistence of polyanhydride nanoparticles as a function of nanoparticle chemistry and administration route. Our observations indicated that the route of administration differentially affected tissue residence times. All nanoparticles rapidly dispersed when delivered intranasally but provided a depot when administered parenterally. When amphiphilic and hydrophobic nanoparticles were administered intranasally, they persisted within lung tissue. These results provide insights into the chemistry- and route-dependent distribution and tissue-specific association of polyanhydride nanoparticle-based vaccine adjuvants.

  1. Correlates of protection, antigen delivery and molecular epidemiology: basics for designing an HIV vaccine.

    PubMed

    Wagner, R; Shao, Y; Wolf, H

    1999-03-26

    Major obstacles in the development of HIV vaccines are the high variability of the virus and its complex interaction with the immune system. Recent studies demonstrated, that CTLs recognizing highly conserved epitopes in the group-specific antigen are capable of controlling HIV-replication in long-term nonprogressors. Necessary consequences for novel vaccine concepts are the presentation of a large repertoire of antigenic sites as well as the stimulation of different effectors of the immune system. Accordingly, different types of recombinant HIV-1 virus-like particles (VLPs) have been constructed stimulating the induction of neutralizing antibodies and HIV-specific CD8-positive CTL responses in preclinical studies. With respect to future vaccine trials, HIV vaccine formulations may need to be tailored to the local strains circulating within a geographical region. The expert group of the joint United Nations Programme on AIDS recently identified Yunnan, a southwestern province of China, as a region, in which the HIV epidemic is starting to gain speed, resembling to the situation in Thailand 10 years ago. A molecular clone of a representative virus strain is now available for the development of innovative antigen delivery systems aiming to be evaluated in future clinical vaccine trials throughout this area.

  2. Decrease in delivery room intubation rates after use of nasal intermittent positive pressure ventilation in the delivery room for resuscitation of very low birth weight infants.

    PubMed

    Biniwale, Manoj; Wertheimer, Fiona

    2017-07-01

    The literature supports minimizing duration of invasive ventilation to decrease lung injury in premature infants. Neonatal Resuscitation Program recommended use of non-invasive ventilation (NIV) in delivery room for infants requiring prolonged respiratory support. To evaluate the impact of implementation of non-invasive ventilation (NIV) using nasal intermittent positive pressure ventilation (NIPPV) for resuscitation in very low birth infants. Retrospective study was performed after NIPPV was introduced in the delivery room and compared with infants receiving face mask to provide positive pressure ventilation for resuscitation of very low birth weight infants prior to its use. Data collected from 119 infants resuscitated using NIPPV and 102 infants resuscitated with a face mask in a single institution. The primary outcome was the need for endotracheal intubation in the delivery room. Data was analyzed using IBM SPSS Statistics software version 24. A total of 31% of infants were intubated in the delivery room in the NIPPV group compared to 85% in the Face mask group (p=<0.001). Chest compression rates were 11% in the NIPPV group and 31% in the Face mask group (p<0.001). Epinephrine administration was also lower in NIPPV group (2% vs. 8%; P=0.03). Only 38% infants remained intubated at 24hours of age in the NIPPV group compared to 66% in the Face mask group (p<0.001). Median duration of invasive ventilation in the NIPPV group was shorter (2days) compared to the Face mask group (11days) (p=0.01). The incidence of air-leaks was not significant between the two groups. NIPPV was safely and effectively used in the delivery room settings to provide respiratory support for VLBW infants with less need for intubation, chest compressions, epinephrine administration and subsequent invasive ventilation. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Increased Protection against Pneumococcal Disease by Mucosal Administration of Conjugate Vaccine plus Interleukin-12

    PubMed Central

    Lynch, Joyce M.; Briles, David E.; Metzger, Dennis W.

    2003-01-01

    Streptococcus pneumoniae is a common cause of respiratory tract infections, its main entry route being the nasal mucosa. The recent development of pneumococcal polysaccharide conjugate vaccines has led to a dramatic improvement in protection against invasive disease in infants and children, but these vaccines have been found to be only 50 to 60% protective against bacterial carriage. In this study, we investigated the efficacy of intranasal (i.n.) conjugate vaccine delivery using interleukin-12 (IL-12) as a mucosal adjuvant. Immunized mice treated with IL-12 demonstrated increased expression of lung and splenic gamma interferon and IL-10 mRNAs; high levels of antibody, particularly serum immunoglobulin G2a (IgG2a) and respiratory IgA; and significantly increased opsonic activity. After intraperitoneal challenge with type 3 pneumococci, there was 75% survival of i.n. vaccinated mice compared to 0% survival of unvaccinated mice. In addition, after i.n. challenge with type 14 pneumococci, vaccinated mice possessed fewer bacterial colonies in the upper respiratory tract than unvaccinated mice. However, no significant difference in type 14 carriage was observed between vaccinated and unvaccinated groups following intramuscular vaccination, the typical route of vaccination in humans. Using mice with a genetic disruption in IgA expression, it was found that pneumococcus-specific IgA played a significant role in the clearance of bacteria from the upper respiratory tract. We conclude that i.n vaccination in the presence of IL-12 is able to enhance systemic and mucosal immune responses to pneumococci and efficiently protect against both invasive infection and bacterial carriage. PMID:12874361

  4. Objective Measure of Nasal Air Emission Using Nasal Accelerometry

    ERIC Educational Resources Information Center

    Cler, Meredith J.; Lien, Yu-An, S.; Braden, Maia N.; Mittleman, Talia; Downing, Kerri; Stepp, Cara, E.

    2016-01-01

    Purpose: This article describes the development and initial validation of an objective measure of nasal air emission (NAE) using nasal accelerometry. Method: Nasal acceleration and nasal airflow signals were simultaneously recorded while an expert speech language pathologist modeled NAEs at a variety of severity levels. In addition, microphone and…

  5. Poly(Lactic Acid) Nanoparticles Targeting α5β1 Integrin as Vaccine Delivery Vehicle, a Prospective Study

    PubMed Central

    Gutjahr, Alice; Terrat, Céline; Exposito, Jean-Yves; Verrier, Bernard; Lethias, Claire

    2016-01-01

    Biodegradable polymeric nanoparticles are vehicles of choice for drug delivery and have the ability to encapsulate and present at their surface different molecules of interest. Among these bio-nanocarriers, poly(lactic acid) (PLA) nanoparticles have been used as adjuvant and vehicle for enhanced vaccine efficacy. In order to develop an approach to efficient vaccine delivery, we developed nanoparticles to target α5β1 positive cells. We first overproduced, in bacteria, human fibronectin FNIII9/10 recombinant proteins possessing an integrin α5β1 binding site, the RGDS sequence, or a mutated form of this site. After having confirmed the integrin binding properties of these recombinant proteins in cell culture assays, we were able to formulate PLA nanoparticles with these FNIII9/10 proteins at their surface. We then confirmed, by fluorescence and confocal microscopy, an enhanced cellular uptake by α5β1+ cells of RGDS-FNIII9/10 coated PLA nanoparticles, in comparison to KGES-FNIII9/10 coated or non-coated controls. As a first vaccination approach, we prepared PLA nanoparticles co-coated with p24 (an HIV antigen), and RGDS- or KGES-FNIII9/10 proteins, followed by subcutaneous vaccine administration, in mice. Although we did not detect improvements in the apparent humoral response to p24 antigen in the serum of RGDS/p24 nanoparticle-treated mice, the presence of the FNIII proteins increased significantly the avidity index of anti-p24 antibodies compared to p24-nanoparticle-injected control mice. Future developments of this innovative targeted vaccine are discussed. PMID:27973577

  6. Immunotherapeutic efficacy of liposome-encapsulated refined allergen vaccines against Dermatophagoides pteronyssinus allergy.

    PubMed

    Chaisri, Urai; Tungtrongchitr, Anchalee; Indrawattana, Nitaya; Meechan, Panisara; Phurttikul, Watchara; Tasaniyananda, Natt; Saelim, Nawannaporn; Chaicumpa, Wanpen; Sookrung, Nitat

    2017-01-01

    Allergen specific immunotherapy (AIT) can modulate the allergic response causing a long-term symptom subsidence/abolishment which leads to reduced drug use and prevention of new sensitization. AIT of house dust mite allergy (HDM) using the mite crude extract (CE) as the therapeutic agent is not only less effective than the AIT for many other allergens, but also frequently causes adverse effects during the treatment course. In this study, mouse model of Dermatophagoides pteronyssinus (Dp) allergy was invented for testing therapeutic efficacies of intranasally administered liposome (L) encapsulated vaccines made of single Dp major allergens (L-Der p 1, L-Der p 2), combined allergens (L-Der p 1 and Der p 2), and crude Dp extract (L-CE). The allergen sparing intranasal route was chosen as it is known that the effective cells induced at the nasal-associated lymphoid tissue can exert their activities at the lower respiratory tissue due to the common mucosal traffic. Liposome was chosen as the vaccine delivery vehicle and adjuvant as the micelles could reduce toxicity of the entrapped cargo. The Dp-CE allergic mice received eight doses of individual vaccines/placebo on alternate days. All vaccine formulations caused reduction of the Th2 response of the Dp allergic mice. However, only the vaccines made of single refined allergens induced expressions of immunosuppressive cytokines (TGF-β, IL-35 and/or IL-10) which are the imperative signatures of successful AIT. The data emphasize the superior therapeutic efficacy of single refined major allergen vaccines than the crude allergenic extract vaccine.

  7. Evaluation of polyvinylidene fluoride nasal sensor to assess deviated nasal septum in comparision with peak nasal inspiratory flow measurements.

    PubMed

    Manjunatha, Roopa G; Rajanna, K; Mahapatra, D Roy; Prakash, Surya

    2014-01-01

    Deviated nasal septum (DNS) is one of the major causes of nasal obstruction. Polyvinylidene fluoride (PVDF) nasal sensor is the new technique developed to assess the nasal obstruction caused by DNS. This study evaluates the PVDF nasal sensor measurements in comparison with PEAK nasal inspiratory flow (PNIF) measurements and visual analog scale (VAS) of nasal obstruction. Because of piezoelectric property, two PVDF nasal sensors provide output voltage signals corresponding to the right and left nostril when they are subjected to nasal airflow. The peak-to-peak amplitude of the voltage signal corresponding to nasal airflow was analyzed to assess the nasal obstruction. PVDF nasal sensor and PNIF were performed on 30 healthy subjects and 30 DNS patients. Receiver operating characteristic was used to analyze the DNS of these two methods. Measurements of PVDF nasal sensor strongly correlated with findings of PNIF (r = 0.67; p < 0.01) in DNS patients. A significant difference (p < 0.001) was observed between PVDF nasal sensor measurements and PNIF measurements of the DNS and the control group. A cutoff between normal and pathological of 0.51 Vp-p for PVDF nasal sensor and 120 L/min for PNIF was calculated. No significant difference in terms of sensitivity of PVDF nasal sensor and PNIF (89.7% versus 82.6%) and specificity (80.5% versus 78.8%) was calculated. The result shows that PVDF measurements closely agree with PNIF findings. Developed PVDF nasal sensor is an objective method that is simple, inexpensive, fast, and portable for determining DNS in clinical practice.

  8. Oral Delivery of Probiotics Expressing Dendritic Cell-Targeting Peptide Fused with Porcine Epidemic Diarrhea Virus COE Antigen: A Promising Vaccine Strategy against PEDV.

    PubMed

    Wang, Xiaona; Wang, Li; Huang, Xuewei; Ma, Sunting; Yu, Meiling; Shi, Wen; Qiao, Xinyuan; Tang, Lijie; Xu, Yigang; Li, Yijing

    2017-10-25

    Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, is the causative agent of porcine epidemic diarrhea (PED) that damages intestinal epithelial cells and results in severe diarrhea and dehydration in neonatal suckling pigs with up to 100% mortality. The oral vaccine route is reported as a promising approach for inducing protective immunity against PEDV invasion. Furthermore, dendritic cells (DCs), professional antigen-presenting cells, link humoral and cellular immune responses for homeostasis of the intestinal immune environment. In this study, in order to explore an efficient oral vaccine against PEDV infection, a mucosal DC-targeting oral vaccine was developed using Lactobacillus casei to deliver the DC-targeting peptide (DCpep) fused with the PEDV core neutralizing epitope (COE) antigen. This probiotic vaccine could efficiently elicit secretory immunoglobulin A (SIgA)-based mucosal and immunoglobulin G (IgG)-based humoral immune responses via oral vaccination in vivo. Significant differences ( p < 0.05) in the immune response levels were observed between probiotics expressing the COE-DCpep fusion protein and COE antigen alone, suggesting better immune efficiency of the probiotics vaccine expressing the DC-targeting peptide fused with PEDV COE antigen. This mucosal DC-targeting oral vaccine delivery effectively enhances vaccine antigen delivery efficiency, providing a useful strategy to induce efficient immune responses against PEDV infection.

  9. Oral delivery of BCG Moreau Rio de Janeiro gives equivalent protection against tuberculosis but with reduced pathology compared to parenteral BCG Danish vaccination.

    PubMed

    Clark, Simon O; Kelly, Dominic L F; Badell, Edgar; Castello-Branco, Luiz Roberto; Aldwell, Frank; Winter, Nathalie; Lewis, David J M; Marsh, Philip D

    2010-10-08

    There is a need for an improved vaccine to better control human tuberculosis (TB), as the only currently available TB vaccine, bacillus Calmette-Guerin (BCG) delivered parenterally, offers variable levels of efficacy. Therefore, recombinant strains expressing additional antigens are being developed alongside alternative routes to parenteral delivery. There is strong evidence that BCG Moreau (RdJ) is a safe and effective vaccine in humans when given by the oral route. This study compared the efficacy of a single oral dose of wild type BCG Moreau Rio de Janeiro (RdJ), or a recombinant RdJ strain expressing Ag85B-ESAT6 fusion protein, formulated with and without lipid to enhance oral delivery, with subcutaneous BCG Danish 1331 and saline control groups in a guinea pig aerosol infection model of pulmonary tuberculosis. Protection was measured as survival at 30 weeks post-challenge and reduced bacterial load and histopathology in lungs and spleen. Results showed that a single oral dose of BCG Moreau (RdJ) or recombinant BCG Moreau (RdJ)-Ag85B-ESAT6, formulated with or without lipid, gave protection equivalent to subcutaneously delivered BCG Danish in the 30 weeks post-challenge survival study. The orally delivered vaccines gave reduced pathology scores in the lungs (three of the four formulations) and spleens (all four formulations) compared to subcutaneously delivered BCG Danish. The oral wild type BCG Moreau (RdJ) in lipid and the unformulated oral wild type BCG Moreau (RdJ) vaccine also gave statistically lower bacterial loads in the lungs and spleens, respectively, compared to subcutaneously delivered BCG Danish. This study provides further evidence to show that lipid formulation does not impair vaccine efficacy and may enhance the delivery and stability of oral vaccines intended for use in countries with poor health infrastructure. Oral delivery also avoids needles (and associated cross-infection risks) and immunisation without the need for specially trained

  10. Engineering T7 bacteriophage as a potential DNA vaccine targeting delivery vector.

    PubMed

    Xu, Hai; Bao, Xi; Wang, Yiwei; Xu, Yue; Deng, Bihua; Lu, Yu; Hou, Jibo

    2018-03-20

    DNA delivery with bacteriophage by surface-displayed mammalian cell penetrating peptides has been reported. Although, various phages have been used to facilitate DNA transfer by surface displaying the protein transduction domain of human immunodeficiency virus type 1 Tat protein (Tat peptide), no similar study has been conducted using T7 phage. In this study, we engineeredT7 phage as a DNA targeting delivery vector to facilitate cellular internalization. We constructed recombinant T7 phages that displayed Tat peptide on their surface and carried eukaryotic expression box (EEB) as a part of their genomes (T7-EEB-Tat). We demonstrated that T7 phage harboring foreign gene insertion had packaged into infective progeny phage particles. Moreover, when mammalian cells that were briefly exposed to T7-EEB-Tat, expressed a significant higher level of the marker gene with the control cells infected with the wide type phage without displaying Tat peptides. These data suggested that the potential of T7 phage as an effective delivery vector for DNA vaccine transfer.

  11. Potent Immune Responses in Rhesus Macaques Induced by Nonviral Delivery of a Self-amplifying RNA Vaccine Expressing HIV Type 1 Envelope With a Cationic Nanoemulsion

    PubMed Central

    Bogers, Willy M.; Oostermeijer, Herman; Mooij, Petra; Koopman, Gerrit; Verschoor, Ernst J.; Davis, David; Ulmer, Jeffrey B.; Brito, Luis A.; Cu, Yen; Banerjee, Kaustuv; Otten, Gillis R.; Burke, Brian; Dey, Antu; Heeney, Jonathan L.; Shen, Xiaoying; Tomaras, Georgia D.; Labranche, Celia; Montefiori, David C.; Liao, Hua-Xin; Haynes, Barton; Geall, Andrew J.; Barnett, Susan W.

    2015-01-01

    Self-amplifying messenger RNA (mRNA) of positive-strand RNA viruses are effective vectors for in situ expression of vaccine antigens and have potential as a new vaccine technology platform well suited for global health applications. The SAM vaccine platform is based on a synthetic, self-amplifying mRNA delivered by a nonviral delivery system. The safety and immunogenicity of an HIV SAM vaccine encoding a clade C envelope glycoprotein formulated with a cationic nanoemulsion (CNE) delivery system was evaluated in rhesus macaques. The HIV SAM vaccine induced potent cellular immune responses that were greater in magnitude than those induced by self-amplifying mRNA packaged in a viral replicon particle (VRP) or by a recombinant HIV envelope protein formulated with MF59 adjuvant, anti-envelope binding (including anti-V1V2), and neutralizing antibody responses that exceeded those induced by the VRP vaccine. These studies provide the first evidence in nonhuman primates that HIV vaccination with a relatively low dose (50 µg) of formulated self-amplifying mRNA is safe and immunogenic. PMID:25234719

  12. Development of a Transnasal Delivery System for Recombinant Human Growth Hormone (rhGH): Effects of the Concentration and Molecular Weight of Poly-L-arginine on the Nasal Absorption of rhGH in Rats.

    PubMed

    Kawashima, Ryo; Uchida, Masaki; Yamaki, Tsutomu; Ohtake, Kazuo; Hatanaka, Tomomi; Uchida, Hiroyuki; Ueda, Hideo; Kobayashi, Jun; Morimoto, Yasunori; Natsume, Hideshi

    2016-01-01

    A novel system for delivering recombinant human growth hormone (rhGH) that is noninvasive and has a simple method of administration is strongly desired to improve the compliance of children. The aim of this study was to investigate the potential for the intranasal (i.n.) co-administration of rhGH with poly-L-arginine (PLA) as a novel delivery system by evaluating the effects of the concentration and molecular weight of PLA on the nasal absorption of rhGH. The influence of the formation of insoluble aggregates and a soluble complex in the dosage formulation on nasal rhGH absorption was also evaluated by size-exclusion chromatography and ultrafiltration. PLA enhanced the nasal absorption of rhGH at each concentration and molecular weight examined. Nasal rhGH absorption increased dramatically when the PLA concentration was 1.0 % (w/v) due to the improved solubility of rhGH in the formulation. A delay in rhGH absorption was observed when the molecular weight of PLA was increased. This appeared to be because the increase in molecular weight caused the formation of a soluble complex. It seems that the PLA concentration affects the absorption-enhancing effect on rhGH, while the molecular weight of PLA affects the time when the maximum plasma rhGH concentration was reached (Tmax) of rhGH after i.n. administration, mainly because of the interactions among rhGH, PLA, and additives. Therefore, the transnasal rhGH delivery system using PLA is considered to be a promising alternative to subcutaneous (s.c.) injection if these interactions are sufficiently controlled.

  13. Transdermal drug delivery

    PubMed Central

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

  14. Vaccinating high-risk children with the intranasal live-attenuated influenza vaccine: the Quebec experience.

    PubMed

    Quach, Caroline

    2014-12-01

    Given the burden of illness associated with influenza, vaccination is recommended for individuals at high risk of complications. The live-attenuated influenza vaccine (LAIV) is administered by intranasal spray, thus directly stimulating mucosal immunity. In this review, we aimed to provide evidence for its efficacy and safety in different paediatric populations. We also share the Quebec experience of LAIV use through a publicly funded vaccination program for children with chronic, high-risk conditions. from randomized controlled trials in healthy children and in asthmatics have demonstrated superior efficacy of LAIV over the injectable vaccine (IIV). LAIV is well tolerated: its administration is associated with runny nose and nasal congestion, but not with asthma exacerbations and is well tolerated in children with cystic fibrosis, when compared to IIV. The vaccine is well accepted by children and parents and can easily be part of vaccination clinics in paediatric tertiary care centres targeting children with chronic, high-risk conditions, not leading to immunosuppression. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. A human papillomavirus type 16 vaccine by oral delivery of L1 protein.

    PubMed

    Sasagawa, Toshiyuki; Tani, Mayuko; Basha, Walid; Rose, Robert C; Tohda, Hideki; Giga-Hama, Yuko; Azar, Khadijeh K; Yasuda, Hideyo; Sakai, Akemi; Inoue, Masaki

    2005-06-01

    To establish an edible HPV16 vaccine, we constructed a recombinant HPV16 L1-expressing Schizosaccharomyces pombe yeast strain (HPV16L1 yeast). A preliminary study revealed that freeze-dried yeast cells could be delivered safely, and were digested in the mouse intestine. The freeze-dried HPV16 L1 yeast was administered orally as an edible vaccine, with or without the mucosal adjuvant heat-labile toxin LT (R192G), to 18 female BALB/c mice. After the third immunization, none of the mice that received the edible HPV16 vaccine showed specific antibody responses, whereas all of the positive controls that were administered intranasally with 5 microg of HPV16-virus-like particles (VLP) had serum IgG, and genital IgA and IgG that reacted with HPV16-VLP in enzyme-linked immunosorbent assays (ELISAs). When a suboptimal dose (1 microg) of HPV16-VLP was administered to all the mice, including the negative control mice, 50% of the mice that were pre-immunized with the edible HPV16 vaccine showed positive serum IgG responses, while none of the negative controls showed any response. Vaginal IgG and IgA antibodies were also elicited in 33 and 39%, respectively, of the mice that were given with the edible HPV16 vaccine and the intranasal boost. All of the antibodies reacted more strongly to intact HPV16-VLP than to denatured HPV16-L1 protein suggesting that the edible vaccine primes for antibody responses against conformation-dependent epitopes. The inclusion of adjuvant in the vaccine formulation marginally increased the genital IgA response (P=0.06). HPV16-L1 protein in the yeast might induce tolerance in the vaccinated animals that could be recovered by intranasal boosting with a suboptimal dose of HPV-VLP. This freeze-dried yeast system may be useful as an oral delivery of HPV 16 L1 protein.

  16. Surface-functionalized, pH-responsive poly(lactic-co-glycolic acid)-based microparticles for intranasal vaccine delivery: Effect of surface modification with chitosan and mannan.

    PubMed

    Li, Ze; Xiong, Fangfang; He, Jintian; Dai, Xiaojing; Wang, Gaizhen

    2016-12-01

    In the present study, surface-functionalized, pH-responsive poly(lactic-co-glycolic acid) (PLGA) microparticles were investigated for nasal delivery of hepatitis B surface Antigen (HBsAg). pH-responsive PLGA, chitosan modified PLGA (CS-PLGA), mannan modified PLGA (MN-PLGA), mannan and chitosan co-modified PLGA (MN-CS-PLGA) microparticles were prepared utilizing a double-emulsion method. Antigen was released rapidly from four types of microparticles at pH5.0 and pH 6.0, but slowly released at pH 7.4. Mannan and chitosan surface modification enhanced intracellular microparticle uptake by macrophages. Following intracellular macrophage antigen uptake, antigen release occurred in three different patterns: fast release from PLGA and MN-PLGA microparticles in endosomes/lysosomes, slow release from CS-PLGA microparticles in cytoplasm and a combination of fast release and slow release patterns from MN-CS-PLGA microparticles. Furthermore, chitosan coating modification increased the residence time of CS-PLGA and MN-CS-PLGA microparticles in the nasal cavity. In vivo immunogenicity studies indicated that MN-CS-PLGA microparticles induced stronger humoral and cell-mediated immune responses compared with PLGA, MN-PLGA and CS-PLGA microparticles. These results suggest that surface modification of pH-responsive PLGA microparticles with mannan and chitosan is a promising tool for nasal delivery of HBsAg. Copyright © 2016. Published by Elsevier B.V.

  17. Similarity and Enhancement: Nasality from Moroccan Arabic Pharyngeals and Nasals

    ERIC Educational Resources Information Center

    Zellou, Georgia Eve

    2012-01-01

    Experimental studies of the articulation, acoustics, and perception of nasal and pharyngeal consonants and adjacent vowels were conducted to investigate nasality in Moroccan Arabic (MA). The status of nasality in MA is described as coarticulatorily complex, where two phoneme types (pharyngeal segments and nasal segments) yield similar…

  18. Canine model of nasal congestion and allergic rhinitis.

    PubMed

    Tiniakov, Ruslan L; Tiniakova, Olga P; McLeod, Robbie L; Hey, John A; Yeates, Donovan B

    2003-05-01

    The ragweed- and histamine-induced decreases in nasal patency in cohorts of ragweed-sensitized and nonsensitized dogs were assessed. The volume of nasal airways (V(NA)) was assessed by acoustic rhinometry and resistance to airflow (R(NA)) by anterior rhinomanometry. Histamine delivered to the nasal passages of five dogs caused a rapid and prolonged increase in R(NA) (0.75 +/- 0.26 to 3.56 +/- 0.50 cmH(2)O. l(-1). min), an effect that was reversed by intranasal delivery of aerosolized phenylephrine. Ragweed challenge in five ragweed-sensitized dogs increased R(NA) from 0.16 +/- 0.02 to 0.53 +/- 0.07 cmH(2)O. l(-1). min and decreased V(NA) from 12.5 +/- 1.9 to 3.9 +/- 0.3 cm(3), whereas administration of saline aerosol neither increased R(NA) nor decreased V(NA). Prior administration of d-pseudoephedrine (30 mg po) attenuated the ragweed-induced increase in R(NA) and decrease in V(NA). Ragweed challenge changed neither R(NA) nor V(NA) in four nonsensitized dogs. Mediator-induced nasal congestion and allergen-induced allergic rhinitis in ragweed-sensitized dogs, which exhibit symptoms similar to human disease, can be used in the evaluation of safety and efficacy of antiallergic activity of potential drugs.

  19. Bolstering Components of the Immune Response Compromised by Prior Exposure to Adenovirus: Guided Formulation Development for a Nasal Ebola Vaccine

    PubMed Central

    2014-01-01

    The severity and longevity of the current Ebola outbreak highlight the need for a fast-acting yet long-lasting vaccine for at-risk populations (medical personnel and rural villagers) where repeated prime-boost regimens are not feasible. While recombinant adenovirus (rAd)-based vaccines have conferred full protection against multiple strains of Ebola after a single immunization, their efficacy is impaired by pre-existing immunity (PEI) to adenovirus. To address this important issue, a panel of formulations was evaluated by an in vitro assay for their ability to protect rAd from neutralization. An amphiphilic polymer (F16, FW ∼39,000) significantly improved transgene expression in the presence of anti-Ad neutralizing antibodies (NAB) at concentrations of 5 times the 50% neutralizing dose (ND50). In vivo performance of rAd in F16 was compared with unformulated virus, virus modified with poly(ethylene) glycol (PEG), and virus incorporated into poly(lactic-co-glycolic) acid (PLGA) polymeric beads. Histochemical analysis of lung tissue revealed that F16 promoted strong levels of transgene expression in naive mice and those that were exposed to adenovirus in the nasal cavity 28 days prior to immunization. Multiparameter flow cytometry revealed that F16 induced significantly more polyfunctional antigen-specific CD8+ T cells simultaneously producing IFN-γ, IL-2, and TNF-α than other test formulations. These effects were not compromised by PEI. Data from formulations that provided partial protection from challenge consistently identified specific immunological requirements necessary for protection. This approach may be useful for development of formulations for other vaccine platforms that also employ ubiquitous pathogens as carriers like the influenza virus. PMID:25549696

  20. A novel "in-feed" delivery platform applied for oral DNA vaccination against IPNV enables high protection in Atlantic salmon (Salmon salar).

    PubMed

    Reyes, Miguel; Ramírez, Cesar; Ñancucheo, Ivan; Villegas, Ricardo; Schaffeld, Guillermo; Kriman, Luis; Gonzalez, Javier; Oyarzun, Patricio

    2017-01-23

    DNA vaccination has emerged as a promising tool against infectious diseases of farmed fish. Oral delivery allows stress-free administration that is ideal for mass immunization and of paramount importance for infectious pancreatic necrosis (IPN) and other viral disease that affect young salmonids and cause economic losses in aquaculture worldwide. We describe the development and in vivo assessment of an "in-feed" formulation strategy for oral immunization with liposomal DNA vaccines, by delivering a vaccine construct coding for an immunogenic region of the VP2 capsid protein. A challenge against IPNV was carried out to determine the vaccine efficacy, by comparing the mortality of pre-smolt Atlantic salmons immunized and non-immunized with the oral vaccine. The antibody response (ELISA) and hematological parameters after immunization were examined, as well as the vaccine effect on the growth and internal structures of fry salmons (histological analysis). The vaccine distribution in the experimental tank after oral administration was investigated by HPLC and PCR amplification. The oral vaccine induced detectable levels of VP2-specific antibodies and conferred significant protection following IPNV challenge, with relative percent survivals (RPS) of 58.2%, for single dose (1mg pDNA /kg fish ⋅d), and 66% for double dose (2mg pDNA /kg fish ⋅d). We further provide evidence in favour of the vaccine safety to fish and demonstrated absence of pDNA in the tank water, but presence of vaccine residues in faeces and unconsumed feed sediments (solid wastes). The delivery platform for liposomal DNA vaccination via feed was successfully proved against IPNV in Atlantic salmon, showing the oral vaccine to be immunogenic and safe for fish, and providing significant protection after oral administration. The "in-feed" technology for oral DNA vaccination holds potential to be applied against IPNV and other pathogens that currently threaten the aquaculture worldwide. Copyright © 2016

  1. [From new vaccine to new target: revisiting influenza vaccination].

    PubMed

    Gérard, M

    2011-09-01

    Annual vaccination is since many years the corner stone of Influenza control strategy. Because conventional vaccine are needle-based, are less immunogenic in old people and induce only systemic IgG production, intranasal and intradermal vaccines that are recently or will be soon available in Belgium will offer distinct advantages. Intradermal vaccination is on the Belgian market since 2010. A stronger immune response that allows an antigen sparing strategy is elicited because antigens are delivered near the dermal dendritic cells. Local side effects are more pronounced than after intramuscular injection. The needle-free intranasal vaccine that has been approved for use in people less than 18 years old by the EMEA in October 2010 induces also a mucosal IgA response. Improved clinical results than with intramuscular vaccine has been documented in several studies in children. Several conditions are contraindication to nasal vaccination because of patterns of side effects and because the vaccine is an live-attenuated vaccine. Pregnant women has become a top priority for Influenza vaccination in the recommendations of the High Council of Health in Belgium since the 2009 H1N1 pandemic. Several studies has since then documented the increased risk for Influenza-related morbidity in pregnant women especially during the third trimester and independently of the presence of other comorbidities. Reduced incidence of documented Influenza and of Influenza-related hospitalizations are observed in the new born of vaccinated women until 6 months of age. Availability of new vaccines for Influenza and better knowledge of the benefit of vaccination in target populations are important tools to optimize vaccine coverage of the population.

  2. Saline nasal washes

    MedlinePlus

    ... nasal wash helps flush pollen, dust, and other debris from your nasal passages. It also helps remove excess mucus (snot) and adds moisture. Your nasal passages are open spaces behind your nose. Air passes through your nasal ...

  3. Self-amplifying mRNA vaccines.

    PubMed

    Brito, Luis A; Kommareddy, Sushma; Maione, Domenico; Uematsu, Yasushi; Giovani, Cinzia; Berlanda Scorza, Francesco; Otten, Gillis R; Yu, Dong; Mandl, Christian W; Mason, Peter W; Dormitzer, Philip R; Ulmer, Jeffrey B; Geall, Andrew J

    2015-01-01

    This chapter provides a brief introduction to nucleic acid-based vaccines and recent research in developing self-amplifying mRNA vaccines. These vaccines promise the flexibility of plasmid DNA vaccines with enhanced immunogenicity and safety. The key to realizing the full potential of these vaccines is efficient delivery of nucleic acid to the cytoplasm of a cell, where it can amplify and express the encoded antigenic protein. The hydrophilicity and strong net negative charge of RNA impedes cellular uptake. To overcome this limitation, electrostatic complexation with cationic lipids or polymers and physical delivery using electroporation or ballistic particles to improve cellular uptake has been evaluated. This chapter highlights the rapid progress made in using nonviral delivery systems for RNA-based vaccines. Initial preclinical testing of self-amplifying mRNA vaccines has shown nonviral delivery to be capable of producing potent and robust innate and adaptive immune responses in small animals and nonhuman primates. Historically, the prospect of developing mRNA vaccines was uncertain due to concerns of mRNA instability and the feasibility of large-scale manufacturing. Today, these issues are no longer perceived as barriers in the widespread implementation of the technology. Currently, nonamplifying mRNA vaccines are under investigation in human clinical trials and can be produced at a sufficient quantity and quality to meet regulatory requirements. If the encouraging preclinical data with self-amplifying mRNA vaccines are matched by equivalently positive immunogenicity, potency, and tolerability in human trials, this platform could establish nucleic acid vaccines as a versatile new tool for human immunization. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Vaccine delivery to the oral cavity using coated microneedles induces systemic and mucosal immunity

    PubMed Central

    Ma, Yunzhe; Tao, Wenqian; Krebs, Shelly J.; Sutton, William F.; Haigwood, Nancy L.; Gill, Harvinder S.

    2014-01-01

    Purpose The objective of this study is to evaluate the feasibility of using coated microneedles to deliver vaccines into the oral cavity to induce systemic and mucosal immune responses. Method Microneedles were coated with sulforhodamine, ovalbumin and two HIV antigens. Coated microneedles were inserted into the inner lower lip and dorsal surface of the tongue of rabbits. Histology was used to confirm microneedle insertion, and systemic and mucosal immune responses were characterized by measuring antigen-specific immunoglobulin G (IgG) in serum and immunoglobulin A (IgA) in saliva, respectively. Results Histological evaluation of tissues shows that coated microneedles can penetrate the lip and tongue to deliver coatings. Using ovalbumin as a model antigen it was found that the lip and the tongue are equally immunogenic sites for vaccination. Importantly, both sites also induced a significant (p < 0.05) secretory IgA in saliva compared to pre-immune saliva. Microneedle-based oral cavity vaccination was also compared to the intramuscular route using two HIV antigens, a virus-like particle and a DNA vaccine. Microneedle-based delivery to the oral cavity and the intramuscular route exhibited similar (p > 0.05) yet significant (p < 0.05) levels of antigen-specific IgG in serum. However, only the microneedle-based oral cavity vaccination group stimulated a significantly higher (p < 0.05) antigen-specific IgA response in saliva, but not intramuscular injection. Conclusion In conclusion, this study provides a novel method using microneedles to induce systemic IgG and secretory IgA in saliva, and could offer a versatile technique for oral mucosal vaccination. PMID:24623480

  5. [Influenza vaccination. Effectiveness of current vaccines and future challenges].

    PubMed

    Ortiz de Lejarazu, Raúl; Tamames, Sonia

    2015-01-01

    Seasonal influenza is an annual challenge for health-care systems, due to factors such as co-circulation of 2 influenza A subtypes jointly with 2 influenza B lineages; the antigenic drift of these virus, which eludes natural immunity, as well as immunity conferred by vaccination; together with influenza impact in terms of morbidity and mortality. Influenza vaccines have been available for more than 70 years and they have progressed in formulation, production and delivery route. Recommendations on vaccination are focused on those with a higher probability of severe disease, and have a progressively wider coverage, and classically based on inactivated vaccines, but with an increasing importance of attenuated live vaccines. More inactivated vaccines are becoming available, from adyuvanted and virosomal vaccines to intradermal delivery, cell-culture or quadrivalent. Overall vaccine effectiveness is about 65%, but varies depending on characteristics of vaccines, virus, population and the outcomes to be prevented, and ranges from less than 10% to almost 90%. Future challenges are formulations that confer more extensive and lasting protection, as well as increased vaccination coverage, especially in groups such as pregnant women and health-care professionals, as well as being extended to paediatrics. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  6. [Clinical analysis of nasal resistance and pulmonary function testing in patients with chronic nasal-sinusitis and nasal polyps].

    PubMed

    Liao, Hua; Shen, Ying; Wang, Pengjun

    2015-05-01

    To study the pulmonary function and nasal resistance characteristics of patients with chronic nose-sinusitis and nasal polyps (CRSwNP), to explore the evaluation role of nasal resistance in nasal ventilation function and the effect of endoscopic sinus surgery on pulmonary function in patients with CRSwNP. Fifty CRSwNP patients that met the study criteria were selected . The patients were performed endoscopic surgeries according to Messerklinger surgical procedures under general anesthesia. Extent of surgery was based on preoperative CT showing the range of the lesion of disease and endoscopic findings. Perioperative treatments contained intranasal corticosteroids, cephalosporin or penicillin antibiotics, nasal irrigation and other treatments. Main outcome measures included visual analog scale (VAS), endoscopic Lind-Kennedy scores, nasal resistence, pulmonary function in patientsone week before and after surgery, three months and six months after surgery. Pulmonary function includes forced expiratory volume in one second (FEV1), forced vital capacity FEV1/FVC and peak expiratory flow (PEF). The study found that there were significantly positive correlations among VAS score, Lund-Kennedy score and nasal resistance (P < 0.05) in CRSwNP patients, but there is a significantly negative correlation between VAS score, Lund-Kennedy score, nasal resistance and pulmonary function indexes of FEV1, FVC and PEF (P < 0.05). The VAS score, Lund-Kennedy score and nasal resistance values of CRSwNP patients were decreased significantly after comprehensive treatments with nasal endoscopic operation as the major one, the difference was statistically different (P < 0.05). And the pulmonary function indexs (FEV1, FVC, PEF) were significantly increased after surgery in CRSwNP patients. The nasal resistance can objectively and reliably reflect the degree of nasal congestion and the recovery of nasal function in CRSwNP patients after endoscopic sinus surgery. The detection method of nasal

  7. Seasonal influenza vaccines.

    PubMed

    Fiore, Anthony E; Bridges, Carolyn B; Cox, Nancy J

    2009-01-01

    Influenza vaccines are the mainstay of efforts to reduce the substantial health burden from seasonal influenza. Inactivated influenza vaccines have been available since the 1940s and are administered via intramuscular injection. Inactivated vaccines can be given to anyone six months of age or older. Live attenuated, cold-adapted influenza vaccines (LAIV) were developed in the 1960s but were not licensed in the United States until 2003, and are administered via nasal spray. Both vaccines are trivalent preparations grown in eggs and do not contain adjuvants. LAIV is licensed for use in the United States for healthy nonpregnant persons 2-49 years of age.Influenza vaccination induces antibodies primarily against the major surface glycoproteins hemagglutinin (HA) and neuraminidase (NA); antibodies directed against the HA are most important for protection against illness. The immune response peaks at 2-4 weeks after one dose in primed individuals. In previously unvaccinated children <9 years of age, two doses of influenza vaccine are recommended, as some children in this age group have limited or no prior infections from circulating types and subtypes of seasonal influenza. These children require both an initial priming dose and a subsequent booster dose of vaccine to mount a protective antibody response.The most common adverse events associated with inactivated vaccines are sore arm and redness at the injection site; systemic symptoms such as fever or malaise are less commonly reported. Guillian-Barré Syndrome (GBS) was identified among approximately 1 per 100,000 recipients of the 1976 swine influenza vaccine. The risk of influenza vaccine-associated GBS from seasonal influenza vaccine is thought to be at most approximately 1-2 cases per 1 million vaccinees, based on a few studies that have found an association; other studies have found no association.The most common adverse events associated with LAIV are nasal congestion, headache, myalgias or fever. Studies of the

  8. DNA vaccination for cervical cancer; a novel technology platform of RALA mediated gene delivery via polymeric microneedles.

    PubMed

    Ali, Ahlam A; McCrudden, Cian M; McCaffrey, Joanne; McBride, John W; Cole, Grace; Dunne, Nicholas J; Robson, Tracy; Kissenpfennig, Adrien; Donnelly, Ryan F; McCarthy, Helen O

    2017-04-01

    HPV subtypes (16, 18) are associated with the development of cervical cancer, with oncoproteins E6 and E7 responsible for pathogenesis. The goal of this study was to evaluate our 'smart system' technology platform for DNA vaccination against cervical cancer. The vaccination platform brings together two main components; a peptide RALA which condenses DNA into cationic nanoparticles (NPs), and a polymeric polyvinylpyrrolidone (PVP) microneedle (MN) patch for cutaneous delivery of the loaded NPs. RALA condensed E6/E7 DNA into NPs not exceeding 100nm in diameter, and afforded the DNA protection from degradation in PVP. Sera from mice vaccinated with MN/RALA-E6/E7 were richer in E6/E7-specific IgGs, displayed a greater T-cell-mediated TC-1 cytotoxicity and contained more IFN-γ than sera from mice that received NPs intramuscularly. More importantly, MN/RALA-E6/E7 delayed TC-1 tumor initiation in a prophylactic model, and slowed tumor growth in a therapeutic model of vaccination, and was more potent than intramuscular vaccination. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Using a high-flow nasal cannula provides superior results to OxyMask delivery in moderate to severe bronchiolitis: a randomized controlled study.

    PubMed

    Ergul, Ayse Betul; Calıskan, Emrah; Samsa, Hasan; Gokcek, Ikbal; Kaya, Ali; Zararsiz, Gozde Erturk; Torun, Yasemin Altuner

    2018-06-18

    The effectiveness of using a face mask with a small diffuser for oxygen delivery (OxyMask) was compared to use of a high-flow nasal cannula (HFNC) in patients with moderate or severe bronchiolitis.The study population in this open, phase 4, randomized controlled trial consisted of 60 patients aged 1-24 months diagnosed with moderate or severe bronchiolitis and admitted to an intensive care unit (ICU) for oxygen therapy. The patients were randomized into two groups according to the method of oxygen delivery: a diffuser mask group and an HFNC group.There were seven failures in the mask group and none in the HFNC group. The survival probability differed significantly between the two treatment methods (p = 0.009).Time to weaning off oxygen therapy was 56 h in the HFNC group and 96 h in the mask group (p < 0.001). HFNC use decreased the treatment failure rate and the duration of both oxygen therapy and ICU treatment compared to the diffuser mask, which implies that an HFNC should be the first choice for treating patients admitted to the ICU with severe bronchiolitis. What is known: • A high-flow nasal cannula (HFNC) does not significantly reduce the time on oxygen compared to standard therapy in children with moderate to severe bronchiolitis. Observational studies show that, since the introduction of HFNC, fewer children with bronchiolitis need intubation. For children with moderate to severe bronchiolitis there is no proof of its benefit. What Is New: • In children with moderate to severe bronchiolitis, HFNC provides faster and more effective improvement than can be achieved with a diffuser mask.

  10. Nasal drug delivery: Design of a novel mucoadhesive and in situ gelling polymer.

    PubMed

    Menzel, Claudia; Jelkmann, Max; Laffleur, Flavia; Bernkop-Schnürch, Andreas

    2017-01-30

    The aim of the present study was to establish a novel polymeric excipient for liquid nasal dosage forms exhibiting viscosity increasing properties, improved mucoadhesion and stability towards oxidation in solution. In order to achieve this goal, 2-mercaptonicotinic acid was first coupled to l-cysteine by disulfide exchange reaction and after purification directly attached to the polymeric backbone of xanthan gum by carbodiimide mediated amide bond formation. The resulting conjugate was characterized with respect to the amount of coupled ligand, the in situ gelling behavior, mucoadhesive properties and stability towards oxidation. Furthermore, the influence of preactivated polymers on ciliary beat frequency (CBF) of porcine nasal epithelial cells was investigated. Results showed, that 252.52±20.54μmol of the ligand was attached per gram polymer. No free thiol groups could be detected on the polymeric backbone indicating entire preactivation. Rheological investigations of polymer mucus mixtures revealed a 1.7-fold and 2.5-fold enhanced mucoadhesion of entirely preactivated xanthan (Xan-Cys-MNA) compared to thiolated xanthan (Xan-Cys) and unmodified xanthan (Xan). Tensile force evaluation reported a 2.87 and 5.11-fold higher total work of adhesion (TWA) as well as a 1.63 and 2.41-fold higher maximum detachement force of Xan-Cys-MNA compared to Xan-Cys and Xan. In the presence of H 2 O 2 as an oxidizing agent Xan-Cys-MNA showed unlike Xan-Cys no increase in viscosity, indicating high stability towards oxidation. Addition of CaCl 2 to Xan-Cys-MNA solutions caused a decrease in viscosity at nevertheless higher total viscosity. Results from CBF studies proved nasal safety for the novel conjugate. According to these results, entirely preactivated thiolated xanthan gum seems to be a promising excipient for nasal dosage forms in order to improve drug bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Particle-based platforms for malaria vaccines.

    PubMed

    Wu, Yimin; Narum, David L; Fleury, Sylvain; Jennings, Gary; Yadava, Anjali

    2015-12-22

    Recombinant subunit vaccines in general are poor immunogens likely due to the small size of peptides and proteins, combined with the lack or reduced presentation of repetitive motifs and missing complementary signal(s) for optimal triggering of the immune response. Therefore, recombinant subunit vaccines require enhancement by vaccine delivery vehicles in order to attain adequate protective immunity. Particle-based delivery platforms, including particulate antigens and particulate adjuvants, are promising delivery vehicles for modifying the way in which immunogens are presented to both the innate and adaptive immune systems. These particle delivery platforms can also co-deliver non-specific immunostimodulators as additional adjuvants. This paper reviews efforts and advances of the Particle-based delivery platforms in development of vaccines against malaria, a disease that claims over 600,000 lives per year, most of them are children under 5 years of age in sub-Sahara Africa. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Needle-free jet injector intradermal delivery of fractional dose inactivated poliovirus vaccine: Association between injection quality and immunogenicity.

    PubMed

    Resik, Sonia; Tejeda, Alina; Mach, Ondrej; Sein, Carolyn; Molodecky, Natalie; Jarrahian, Courtney; Saganic, Laura; Zehrung, Darin; Fonseca, Magile; Diaz, Manuel; Alemany, Nilda; Garcia, Gloria; Hung, Lai Heng; Martinez, Yenisleydis; Sutter, Roland W

    2015-10-26

    The World Health Organization recommends that as part of the polio end-game strategy a dose of inactivated poliovirus vaccine (IPV) be introduced by the end of 2015 in all countries currently using only oral poliovirus vaccine (OPV). Administration of fractional dose (1/5 of full dose) IPV (fIPV) by intradermal (ID) injection may reduce costs, but its conventional administration is with Bacillus Calmette-Guerin (BCG) needle and syringe (NS), which is time consuming and technically challenging. We compared injection quality achieved with BCG NS and three needle-free jet injectors and assessed ergonomic features of the injectors. Children between 12 and 20 months of age who had previously received OPV were enrolled in the Camaguey, Cuba study. Subjects received a single fIPV dose administered intradermally with BCG NS or one of three needle-free injector devices: Bioject Biojector 2000® (B2000), Bioject ID Pen® (ID Pen), or PharmaJet Tropis® (Tropis). We measured bleb diameter and vaccine loss as indicators of ID injection quality, with desirable injection quality defined as bleb diameter ≥5mm and vaccine loss <10%. We surveyed vaccinators to evaluate ergonomic features of the injectors. We further assessed the injection quality indicators as predictors of immune response, measured by increase in poliovirus neutralizing antibodies in blood between day 0 (pre-IPV) and 21 (post-vaccination). Delivery by BCG NS and Tropis resulted in the highest proportion of subjects with desirable injection quality; health workers ranked Biojector2000 and Tropis highest for ergonomic features. We observed that vaccine loss and desirable injection quality were associated with an immune response for poliovirus type 2 (P=0.02, P=0.01, respectively). Our study demonstrated the feasibility of fIPV delivery using needle-free injector devices with high acceptability among health workers. We did not observe the indicators of injection quality to be uniformly associated with immune

  13. Assessment of nasalance and nasality in patients with a repaired cleft palate.

    PubMed

    Sinko, Klaus; Gruber, Maike; Jagsch, Reinhold; Roesner, Imme; Baumann, Arnulf; Wutzl, Arno; Denk-Linnert, Doris-Maria

    2017-07-01

    In patients with a repaired cleft palate, nasality is typically diagnosed by speech language pathologists. In addition, there are various instruments to objectively diagnose nasalance. To explore the potential of nasalance measurements after cleft palate repair by NasalView ® , we correlated perceptual nasality and instrumentally measured nasalance of eight speech items and determined the relationship between sensitivity and specificity of the nasalance measures by receiver-operating characteristics (ROC) analyses and AUC (area under the curve) computation for each single test item and specific item groups. We recruited patients with a primarily repaired cleft palate receiving speech therapy during follow-up. During a single day visit, perceptive and instrumental assessments were obtained in 36 patients and analyzed. The individual perceptual nasality was assigned to one of four categories; the corresponding instrumental nasalance measures for the eight specific speech items were expressed on a metric scale (1-100). With reference to the perceptual diagnoses, we observed 3 nasal and one oral test item with high sensitivity. However, the specificity of the nasality indicating measures was rather low. The four best speech items with the highest sensitivity provided scores ranging from 96.43 to 100%, while the averaged sensitivity of all eight items was below 90%. We conclude that perceptive evaluation of nasality remains state of the art. For clinical follow-up, instrumental nasalance assessment can objectively document subtle changes by analysis of four speech items only. Further studies are warranted to determine the applicability of instrumental nasalance measures in the clinical routine, using discriminative items only.

  14. Smart delivery of vaccines

    NASA Astrophysics Data System (ADS)

    Melief, Cornelis J. M.

    2018-06-01

    A strategy to enhance antigen immunogenicity was developed by adsorption of polyethyleneimine on a mesoporous silica microrod vaccine for the presentation of tumour viruses and neoantigens, demonstrating their ability to drive anti-tumour immunity.

  15. Using hepatitis A and B vaccination as a paradigm for effective HIV vaccine delivery.

    PubMed

    Rhodes, Scott D; Yee, Leland J

    2007-06-01

    An understanding of vaccine acceptance and uptake is imperative for successful vaccination of populations that will be primary targets for vaccination after a vaccine against HIV is developed and ready for dissemination. Experiences with vaccination against vaccine-preventable hepatitis (VPH) among men who have sex with men (MSM) may offer key insights to inform future HIV vaccination strategies. The purpose of this analysis was to explore what is known currently about vaccination among MSM, using knowledge gained from vaccination against VPH, and to identify important considerations from these experiences that must be explored further as a vaccine against HIV is promoted among MSM. Because cultural and political differences make it difficult to extrapolate findings from studies in one country to another, we have focused our analyses on studies conducted in the USA. Through a qualitative systematic review of published reports, we identified eight studies that reported correlates of VPH among MSM in the USA. Six major domains of variables associated with vaccination against VPH were identified, including: demographics (e.g. younger age, higher educational attainment); increased vaccine knowledge; increased access to health care; provider recommendation; behaviours (e.g. same-sex behaviour, health-promoting and disease-preventing behaviours); and psychosocial factors (e.g. openness about one's sexual orientation, reduced barriers to being vaccinated, self-efficacy). Further research is needed to understand vaccination behaviour among MSM and to maximise acceptance and uptake after a vaccine exists. Experiences with VPH provide a real-world model on which to base preliminary assumptions about acceptance and uptake of a vaccine against HIV.

  16. Langerin negative dendritic cells promote potent CD8+ T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays

    PubMed Central

    Bachy, Veronique; Hervouet, Catherine; Becker, Pablo D.; Chorro, Laurent; Carlin, Leo M.; Herath, Shanthi; Papagatsias, Timos; Barbaroux, Jean-Baptiste; Oh, Sea-Jin; Benlahrech, Adel; Athanasopoulos, Takis; Dickson, George; Patterson, Steven; Kwon, Sung-Yun; Geissmann, Frederic; Klavinskis, Linda S.

    2013-01-01

    Stabilization of virus protein structure and nucleic acid integrity is challenging yet essential to preserve the transcriptional competence of live recombinant viral vaccine vectors in the absence of a cold chain. When coupled with needle-free skin delivery, such a platform would address an unmet need in global vaccine coverage against HIV and other global pathogens. Herein, we show that a simple dissolvable microneedle array (MA) delivery system preserves the immunogenicity of vaccines encoded by live recombinant human adenovirus type 5 (rAdHu5). Specifically, dried rAdHu5 MA immunization induced CD8+ T-cell expansion and multifunctional cytokine responses equipotent with conventional injectable routes of immunization. Intravital imaging demonstrated MA cargo distributed both in the epidermis and dermis, with acquisition by CD11c+ dendritic cells (DCs) in the dermis. The MA immunizing properties were attributable to CD11c+ MHCIIhi CD8αneg epithelial cell adhesion molecule (EpCAMneg) CD11b+ langerin (Lang; CD207)neg DCs, but neither Langerhans cells nor Lang+ DCs were required for CD8+ T-cell priming. This study demonstrates an important technical advance for viral vaccine vectors progressing to the clinic and provides insights into the mechanism of CD8+ T-cell priming by live rAdHu5 MAs. PMID:23386724

  17. Langerin negative dendritic cells promote potent CD8+ T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays.

    PubMed

    Bachy, Veronique; Hervouet, Catherine; Becker, Pablo D; Chorro, Laurent; Carlin, Leo M; Herath, Shanthi; Papagatsias, Timos; Barbaroux, Jean-Baptiste; Oh, Sea-Jin; Benlahrech, Adel; Athanasopoulos, Takis; Dickson, George; Patterson, Steven; Kwon, Sung-Yun; Geissmann, Frederic; Klavinskis, Linda S

    2013-02-19

    Stabilization of virus protein structure and nucleic acid integrity is challenging yet essential to preserve the transcriptional competence of live recombinant viral vaccine vectors in the absence of a cold chain. When coupled with needle-free skin delivery, such a platform would address an unmet need in global vaccine coverage against HIV and other global pathogens. Herein, we show that a simple dissolvable microneedle array (MA) delivery system preserves the immunogenicity of vaccines encoded by live recombinant human adenovirus type 5 (rAdHu5). Specifically, dried rAdHu5 MA immunization induced CD8(+) T-cell expansion and multifunctional cytokine responses equipotent with conventional injectable routes of immunization. Intravital imaging demonstrated MA cargo distributed both in the epidermis and dermis, with acquisition by CD11c(+) dendritic cells (DCs) in the dermis. The MA immunizing properties were attributable to CD11c(+) MHCII(hi) CD8α(neg) epithelial cell adhesion molecule (EpCAM(neg)) CD11b(+) langerin (Lang; CD207)(neg) DCs, but neither Langerhans cells nor Lang(+) DCs were required for CD8(+) T-cell priming. This study demonstrates an important technical advance for viral vaccine vectors progressing to the clinic and provides insights into the mechanism of CD8(+) T-cell priming by live rAdHu5 MAs.

  18. Comparative Safety and Efficacy Profile of a Novel Oil in Water Vaccine Adjuvant Comprising Vitamins A and E and a Catechin in Protective Anti-Influenza Immunity

    PubMed Central

    Patel, Sapna; Faraj, Yasser; Duso, Debra K.; Reiley, William W.; Karlsson, Erik A.; Schultz-Cherry, Stacey; Vajdy, Michael

    2017-01-01

    Non-replicating vaccines, such as those based on recombinant proteins, require adjuvants and delivery systems, which have thus far depended on mimicking pathogen danger signals and strong pro-inflammatory responses. In search of a safer and more efficacious alternative, we tested whether vaccinations with influenza recombinant hemagglutinin (HA) mixed with a novel vegetable oil in water emulsion adjuvant (Natural Immune-enhancing Delivery System, NIDS), based on the immune-enhancing synergy of vitamins A and E and a catechin, could protect against intra-nasal challenge with live influenza virus. Vaccinations of inbred Brag Albino strain c (BALB/c) mice, with HA mixed with NIDS compared to other adjuvants, i.e., a squalene oil in water emulsion (Sq. oil), and the Toll Like Receptor 3 (TLR3) agonist Poly (I:C), induced significantly lower select innate pro-inflammatory responses in serum, but induced significantly higher adaptive antibody and splenic T Helper 1 (TH1) or TH2, but not TH17, responses. Vaccinations with NIDS protected against infection, as measured by clinical scores, lung viral loads, and serum hemagglutination inhibition titers. The NIDS exhibited a strong dose sparing effect and the adjuvant action of NIDS was intact in the outbred CD1 mice. Importantly, vaccinations with the Sq. oil, but not NIDS, induced a significantly higher Serum Amyloid P component, an acute phase reactant secreted by hepatocytes, and total serum IgE. Thus, the NIDS may be used as a clinically safer and more efficacious vaccine adjuvant against influenza, and potentially other infectious diseases. PMID:28531130

  19. Comparative efficacy of intranasal and injectable vaccines in stimulating Bordetella bronchiseptica-reactive anamnestic antibody responses in household dogs

    PubMed Central

    Ellis, John A.; Gow, Sheryl P.; Lee, Lindsey B.; Lacoste, Stacey; Ball, Eileen C.

    2017-01-01

    In order to determine the comparative efficacy of injectable and intranasal vaccines to stimulate Bordetella bronchiseptica (Bb)-reactive anamnestic antibodies, a trial was conducted using 144 adult household dogs of various breeds and ages, which had been previously administered intranasal Bb vaccine approximately 12 months before enrollment. Dogs were randomized into 2 groups and blood, nasal swabs, and pharyngeal swabs were collected prior to the administration of single component Bb vaccines intranasally or parenterally. Ten to 14 days later all dogs were resampled to measure changes in systemic and local antibody to Bb. There were no differences in the changes in Bb-reactive serum IgG and nasal IgA between the groups, whereas intranasally vaccinated dogs had significantly higher Bb-reactive serum IgA. These data indicate that both of the current generation of intranasal (modified-live) and injectable (acellular) Bb vaccines can stimulate anamnestic local and systemic antibody responses in previously vaccinated, Bb-seropositive adult household dogs. PMID:28761185

  20. Potentiation of an anthrax DNA vaccine with electroporation.

    PubMed

    Luxembourg, A; Hannaman, D; Nolan, E; Ellefsen, B; Nakamura, G; Chau, L; Tellez, O; Little, S; Bernard, R

    2008-09-19

    DNA vaccines are a promising method of immunization against biothreats and emerging infections because they are relatively easy to design, manufacture, store and distribute. However, immunization with DNA vaccines using conventional delivery methods often fails to induce consistent, robust immune responses, especially in species larger than the mouse. Intramuscular (i.m.) delivery of a plasmid encoding anthrax toxin protective antigen (PA) using electroporation (EP), a potent DNA delivery method, rapidly induced anti-PA IgG and toxin neutralizing antibodies within 2 weeks following a single immunization in multiple experimental species. The delivery procedure is particularly dose efficient and thus favorable for achieving target levels of response following vaccine administration in humans. These results suggest that EP may be a valuable platform technology for the delivery of DNA vaccines against anthrax and other biothreat agents.

  1. Rationally designed nanocarriers for intranasaltherapy of allergic rhinitis: influence of carrier type on in vivo nasal deposition

    PubMed Central

    Sallam, Marwa Ahmed; Helal, Hala Mahmoud; Mortada, Sana Mohamed

    2016-01-01

    The aim of this study is to develop a locally acting nasal delivery system of triamcinolone acetonide (TA) for the maintenance therapy of allergic rhinitis. The effect of encapsulating TA in different nanocarriers on its mucosal permeation and retention as well as in vivo nasal deposition has been studied. A comparative study was established between polymeric oil core nanocapsules (NCs), lipid nanocarriers such as nanoemulsion (NE), and nanostructured lipid carriers (NLCs). The elaborated nanocarriers were compared with TA suspension and the commercially available suspension “Nasacort®”. The study revealed that NC provided the highest mucosal retention, as 46.14%±0.048% of the TA initial dose was retained after 24 hours, while showing the least permeation through the nasal mucosa. On the other hand, for TA suspension and Nasacort®, the mucosal retention did not exceed 23.5%±0.047% of the initial dose after 24 hours. For NE and NLC, values of mucosal retention were 19.4%±0.041% and 10.97%±0.13%, respectively. NC also showed lower mucosal irritation and superior stability compared with NE. The in vivo nasal deposition study demonstrated that NC maintained drug in its site of action (nasal cavity mucosa) for the longest period of time. The elaborated polymeric oil core NCs are efficient carriers for the administration of nasally acting TA as it produced the least permeation results, thus decreasing systemic absorption of TA. Although NCs have been administered via various routes, this is the first study to implement the polymeric oil core NC as an efficient carrier for localized nasal drug delivery. PMID:27307734

  2. Addressing Health Inequalities in the Delivery of the Human Papillomavirus Vaccination Programme: Examining the Role of the School Nurse

    PubMed Central

    Boyce, Tammy; Holmes, Alison

    2012-01-01

    Background HPV immunisation of adolescent girls is expected to have a significant impact in the reduction of cervical cancer. UK The HPV immunisation programme is primarily delivered by school nurses. We examine the role of school nurses in delivering the HPV immunisation programme and their impact on minimising health inequalities in vaccine uptake. Methods and Findings A rapid evidence assessment (REA) and semi-structured interviews with health professionals were conducted and analysed using thematic analysis. 80 health professionals from across the UK are interviewed, primarily school nurses and HPV immunisation programme coordinators. The REA identified 2,795 articles and after analysis and hand searches, 34 relevant articles were identified and analysed. Interviews revealed that health inequalities in HPV vaccination uptake were mainly related to income and other social factors in contrast to published research which emphasises potential inequalities related to ethnicity and/or religion. Most school nurses interviewed understood local health inequalities and made particular efforts to target girls who did not attend or missed doses. Interviews also revealed maintaining accurate and consistent records influenced both school nurses' understanding and efforts to target inequalities in HPV vaccination uptake. Conclusions Despite high uptake in the UK, some girls remain at risk of not being vaccinated with all three doses. School nurses played a key role in reducing health inequalities in the delivery of the HPV programme. Other studies identified religious beliefs and ethnicity as potentially influencing HPV vaccination uptake but interviews for this research found this appeared not to have occurred. Instead school nurses stated girls who were more likely to be missed were those not in education. Improving understanding of the delivery processes of immunisation programmes and this impact on health inequalities can help to inform solutions to increase uptake and

  3. Systemically administered gp100 encoding DNA vaccine for melanoma using water-in-oil-in-water multiple emulsion delivery systems.

    PubMed

    Kalariya, Mayurkumar; Amiji, Mansoor M

    2013-09-10

    The purpose of this study was to develop a water-in-oil-in-water (W/O/W) multiple emulsions-based vaccine delivery system for plasmid DNA encoding the gp100 peptide antigen for melanoma immunotherapy. The gp100 encoding plasmid DNA was encapsulated in the inner-most aqueous phase of squalane oil containing W/O/W multiple emulsions using a two-step emulsification method. In vitro transfection ability of the encapsulated plasmid DNA was investigated in murine dendritic cells by transgene expression analysis using fluorescence microscopy and ELISA methods. Prophylactic immunization using the W/O/W multiple emulsions encapsulated the gp100 encoding plasmid DNA vaccine significantly reduced tumor volume in C57BL/6 mice during subsequent B16-F10 tumor challenge. In addition, serum Th1 cytokine levels and immuno-histochemistry of excised tumor tissues indicated activation of cytotoxic T-lymphocytes mediated anti-tumor immunity causing tumor growth suppression. The W/O/W multiple emulsions-based vaccine delivery system efficiently delivers the gp100 plasmid DNA to induce cell-mediated anti-tumor immunity. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Exploring new packaging and delivery options for the immunization supply chain.

    PubMed

    Zehrung, Darin; Jarrahian, Courtney; Giersing, Birgitte; Kristensen, Debra

    2017-04-19

    A variety of vaccine packaging and delivery technologies may benefit the immunization supply chain. These include alternative primary packaging, such as blow-fill-seal polymer containers, and novel delivery technologies, such intradermal delivery devices, microarray patches, and sublingual formulations of vaccines, and others in development. The potential timeline to availability of these technologies varies and depends on their stage of development and the type of data necessary to achieve licensure. Some new delivery devices are anticipated to be introduced in 2017, such as intradermal devices for delivery of inactivated poliovirus vaccine to stretch vaccine supplies due to a supply limitation. Other new technologies requiring vaccine reformulation, such as microarray patches and sublingual vaccines, may become available in the long term (2021 and beyond). Development of many new technologies requires partnership between vaccine and technology manufacturers and identification of the applicable regulatory pathway. Interaction with public-sector stakeholders early on (through engagement with forums such as the World Health Organization's Immunization Practices Advisory Committee Delivery Technologies Working Group) is important to ensure suitability for immunization program use. Key considerations for programmatic suitability of a new vaccine, packaging, and delivery device include cold chain volume, costs, and health impact. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Nasal Anatomy and Function.

    PubMed

    Patel, Ruchin G

    2017-02-01

    The nose is a complex structure important in facial aesthetics and in respiratory physiology. Nasal defects can pose a challenge to reconstructive surgeons who must re-create nasal symmetry while maintaining nasal function. A basic understanding of the underlying nasal anatomy is thus necessary for successful nasal reconstruction. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  6. Prospects in nasal vaccination against clinically relevant pathogens and select agents

    USDA-ARS?s Scientific Manuscript database

    Intranasal immunization induces mucosal immune responses in both the respiratory system and at other distant mucosal surfaces, as well as systemic immune responses. However, most vaccines are still given via the parenteral route, and to date, the only intranasal vaccine that is available to the publ...

  7. The efficacy of mobile application use on recall of surgical risks in nasal bone fracture reduction surgery

    PubMed Central

    Kim, Choong Hyeon; Cheon, Ji Seon; Choi, Woo Young; Son, Kyung Min

    2018-01-01

    Background The number of surgical risks recalled by a patient after surgery can be used as a parameter for assessing how well the patient has understood the informed consent process. No study has investigated the usefulness of a self-developed mobile application in the traditional informed consent process in patients with a nasal bone fracture. This study aimed to investigate whether delivery of information, such as surgical risks, through a mobile application is more effective than delivery of information through only verbal means and a paper. Methods This prospective, randomized study included 60 patients with a nasal bone fracture. The experimental group (n=30) received preoperative explanation with the traditional informed consent process in addition to a mobile application, while the control group (n=30) received preoperative explanation with only the traditional informed consent process. Four weeks after surgery, the number of recalled surgical risks was compared for analysis. The following six surgical risks were explained: pain, bleeding, nasal deformity, numbness, nasal obstruction, and nasal cartilage necrosis. Results The mean number of recalled surgical risks among all patients was 1.58±0.56. The most frequently recalled surgical risk was nasal deformity in both groups. The mean number of recalled surgical risks was 1.72±0.52 in the experimental group and 1.49±0.57 in the control group. There was a significant association between mobile application use and the mean number of recalled surgical risks (p=0.047). Age, sex, and the level of education were not significantly associated with the mean number of recalled surgical risks. Conclusion This study found that a mobile application could contribute to the efficient delivery of information during the informed consent process. With further improvement, it could be used in other plastic surgeries and other surgeries, and such an application can potentially be used for explaining risks as well as

  8. The efficacy of mobile application use on recall of surgical risks in nasal bone fracture reduction surgery.

    PubMed

    Kim, Choong Hyeon; Cheon, Ji Seon; Choi, Woo Young; Son, Kyung Min

    2018-03-01

    The number of surgical risks recalled by a patient after surgery can be used as a parameter for assessing how well the patient has understood the informed consent process. No study has investigated the usefulness of a self-developed mobile application in the traditional informed consent process in patients with a nasal bone fracture. This study aimed to investigate whether delivery of information, such as surgical risks, through a mobile application is more effective than delivery of information through only verbal means and a paper. This prospective, randomized study included 60 patients with a nasal bone fracture. The experimental group (n=30) received preoperative explanation with the traditional informed consent process in addition to a mobile application, while the control group (n=30) received preoperative explanation with only the traditional informed consent process. Four weeks after surgery, the number of recalled surgical risks was compared for analysis. The following six surgical risks were explained: pain, bleeding, nasal deformity, numbness, nasal obstruction, and nasal cartilage necrosis. The mean number of recalled surgical risks among all patients was 1.58±0.56. The most frequently recalled surgical risk was nasal deformity in both groups. The mean number of recalled surgical risks was 1.72±0.52 in the experimental group and 1.49±0.57 in the control group. There was a significant association between mobile application use and the mean number of recalled surgical risks ( p =0.047). Age, sex, and the level of education were not significantly associated with the mean number of recalled surgical risks. This study found that a mobile application could contribute to the efficient delivery of information during the informed consent process. With further improvement, it could be used in other plastic surgeries and other surgeries, and such an application can potentially be used for explaining risks as well as delivering other types of information.

  9. Island composite nasal flap for nasal dorsum skin defects.

    PubMed

    Skitarelić, Neven; Mladina, Ranko; Mraovic, Boris; Simurina, Tatjana; Skitarelić, Nataa; Vuković, Katarina

    2009-08-01

    Skin defects on the nasal dorsum remain a challenge for the plastic surgeon. There are few local nasal flap options for the repair of proximally positioned nasal skin defects. During a 3-year period, 22 patients were treated after excision of skin cancer in the proximal two-thirds of the nose. Nine patients (41%) were female and 13 (59%) were male, with an average age of 69 years. All patients were operated on under local anesthesia. The average follow-up was 25 months. In all patients, after tumor ablation, the skin defect was closed with an island composite nasal skin flap. Pathohistologic analysis confirmed that the margins of the removed tumor were free of malignant cells. Six patients (27.3%) had squamous cell and 16 (72.7%) had basal cell carcinoma. There was no total or partial flap loss. None of the patients has suffered from recurrence of the tumor. The island composite nasal flap is a reliable technique for the closure of proximal nasal skin defects. Complications in the elevation of the island composite flap were rare, and the final result was acceptable.

  10. Nanovaccines : nanocarriers for antigen delivery.

    PubMed

    Gonzalez-Aramundiz, Jose Vicente; Cordeiro, Ana Sara; Csaba, Nœmi; de la Fuente, Maria; Alonso, María José

    2012-01-01

    Vaccination has become one of the most important health interventions of our times, revolutionizing health care, and improving the quality of life and life expectancy of millions all over the world. In spite of this, vaccine research remains a vast field for innovation and improvement. Indeed, the shift towards the use of sub-unit antigens, much safer but less immunogenic, and the recognized need to facilitate the access to vaccines in the global framework is currently stimulating the search for safe and efficient adjuvants and delivery technologies. Within this context, nanocarriers have gained particular attention over the last years and appear as one of the most promising strategies for antigen delivery. A number of biomaterials and technologies can be used to design nanovaccines that fulfill the requirements of new vaccination approaches, such as single-dose and transmucosal immunization, critical for achieving a widespread coverage while reducing the overall costs in relation to traditional forms of vaccination. Here we present an overview of the current state of nanocarriers for antigen delivery, developed with the perspective of contributing to the global vaccination goal. © Société de Biologie, 2013.

  11. Correlation of Nasal Mucosal Temperature With Subjective Nasal Patency in Healthy Individuals

    PubMed Central

    Bailey, Ryan S.; Casey, Kevin P.; Pawar, Sachin S.; Garcia, Guilherme J. M.

    2016-01-01

    Importance Historically, otolaryngologists have focused on nasal resistance to airflow and minimum airspace cross-sectional area as objective measures of nasal obstruction using methods such as rhinomanometry and acoustic rhinometry. However, subjective sensation of nasal patency may be more associated with activation of cold receptors by inspired air than with respiratory effort. Objective To investigate whether subjective nasal patency correlates with nasal mucosal temperature in healthy subjects. Design, Setting, and Participants Twenty-two healthy adults were recruited for this study. Subjects first completed the Nasal Obstruction Symptom Evaluation (NOSE) and a unilateral visual analog scale (VAS) to quantify subjective nasal patency. A miniaturized thermocouple sensor was then used to record nasal mucosal temperature bilaterally in two locations along the nasal septum: at the vestibule and across from the inferior turbinate head. Results The range of temperature oscillations during the breathing cycle, defined as the difference between end-expiratory and end-inspiratory temperatures, was greater during deep breaths (ΔTexp-insp = 6.2 ± 2.6°C) than during resting breathing (ΔTexp-insp = 4.2 ± 2.3°C) in both locations (p < 10−13). Mucosal temperature measured at the right vestibule had a statistically significant correlation with both right-side VAS score (Pearson r = −0.55, p=0.0076) and NOSE score (Pearson r = −0.47, p=0.028). No other statistically significant correlations were found between mucosal temperature and subjective nasal patency scores. Nasal mucosal temperature was lower in the first cavity to be measured, which was the right cavity in all subjects. Conclusions and Relevance The greater mucosal temperature oscillations during deep breathing is consistent with the common experience that airflow sensation is enhanced during deep breaths, thus supporting the hypothesis that mucosal cooling plays a central role in nasal airflow sensation

  12. Influence of cooling face masks on nasal air conditioning and nasal geometry.

    PubMed

    Lindemann, J; Hoffmann, T; Koehl, A; Walz, E M; Sommer, F

    2017-06-01

    Nasal geometries and temperature of the nasal mucosa are the primary factors affecting nasal air conditioning. Data on intranasal air conditioning after provoking the trigeminal nerve with a cold stimulus simulating the effects of an arctic condition is still missing. The objective was to investigate the influence of skin cooling face masks on nasal air conditioning, mucosal temperature and nasal geometry. Standardized in vivo measurements of intranasal air temperature, humidity and mucosal temperature were performed in 55 healthy subjects at defined detection sites before and after wearing a cooling face mask. Measurements of skin temperature, rhinomanometry and acoustic rhinometry were accomplished. After wearing the face mask the facial skin temperature was significantly reduced. Intranasal air temperature did not change. Absolute humidity and mucosal temperature increased significantly. The acoustic rhinometric results showed a significant increase of the volumes and the cross-sectional areas. There was no change in nasal airflow. Nasal mucosal temperature, humidity of inhaled air, and volume of the anterior nose increased after application of a cold face mask. The response is mediated by the trigeminal nerve. Increased mucosal temperatures as well as changes in nasal geometries seem to guarantee sufficient steady intranasal nasal air conditioning.

  13. Reduced nasal growth after primary nasal repair combined with cleft lip surgery.

    PubMed

    Yoshimura, Y; Okumoto, T; Iijima, Y; Inoue, Y

    2015-11-01

    Nasal growth after cleft lip surgery with or without primary nasal repair was evaluated using lateral cephalograms. In 14 patients who underwent simultaneous nasal repair with primary cleft lip repair and 12 patients without simultaneous nasal repair, lateral cephalograms were obtained at 5 and 10 years of age. Lateral cephalograms of normal Japanese children were used as a control. At 5 years of age, there were significant differences in the nasal height and columellar angle among the three groups. Children without simultaneous nasal repair had shorter noses with more upward tilt of the columella compared with the controls, while children with simultaneous nasal repair had much shorter noses and more upward tilt than those without repair. At 10 years of age, the children without simultaneous nasal repair showed no differences from the control group, while those with simultaneous repair still had shorter noses and more upward tilt of the columella. These findings suggest that performing nasal repair at the same time as primary cleft lip surgery has an adverse influence on the subsequent growth of the nose. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  14. Intradermal vaccination for infants and children

    PubMed Central

    Saitoh, Akihiko; Aizawa, Yuta

    2016-01-01

    ABSTRACT Intradermal (ID) vaccination induces a more potent immune response and requires lower vaccine doses as compared with standard vaccination routes. To deliver ID vaccines effectively and consistently, an ID delivery device has been developed and is commercially available for adults. The clinical application of ID vaccines for infants and children is much anticipated because children receive several vaccines, on multiple occasions, during infancy and childhood. However, experience with ID vaccines is limited and present evidence is sparse and inconsistent. ID delivery devices are not currently available for infants and children, but recent studies have examined skin thickness in this population and reported that it did not differ in proportion to body size in infants, children, and adults. These results are helpful in developing new ID devices and for preparing new vaccines in infants and children. PMID:27135736

  15. Childhood vaccination: achievements and challenges.

    PubMed

    Ndumbe, P

    1996-09-01

    As the goal of eradicating smallpox was being met, the World Health Organization created its Expanded Programme on Immunisation (EPI) in 1974 and reached its initial goal of achieving full vaccination of 80% of the world's children by 1990. This effort was aided by the creation of "cold chain" delivery systems and resulted in the annual saving of 3.5 million children in less-developed countries. Current EPI vaccination goals include 1) eradication of poliomyelitis by the year 2000, 2) elimination of neonatal tetanus by the year 1995, 3) control of measles and hepatitis B, and 4) immunization of 90% of the world's children 1 year or younger by the year 2000. Goals of the Children's Vaccine Initiative (formed in 1991) include 1) provision of an adequate supply of affordable, safe, and effective vaccines; 2) production of improved and new vaccines; and 3) simplification of the logistics of vaccine delivery. Future challenges are to sustain high vaccination coverage, reach the unreached, achieve proper storage of vaccines and reduce waste, integrate new vaccines into national programs, and achieve vaccine self-sufficiency. The fact that these challenges will be difficult to achieve is illustrated by the situation in Africa where the high immunization levels achieved in 1990 have dropped dramatically. Those who must act to implement immunization programs are health personnel, families, governments, and development partners. In order to achieve equity in health, every child must be reached, governments must be made accountable for programs, health workers must convince families of the importance of vaccination, delivery systems must be in place to take advantage of the new vaccines being delivered, and a multisectoral approach must be taken to assure sustainability.

  16. Specific antibodies induced by nasally administered 40-kDa outer membrane protein of Porphyromonas gingivalis inhibits coaggregation activity of P. gingivalis.

    PubMed

    Namikoshi, Jun; Otake, Shigeo; Maeba, Satomi; Hayakawa, Mitsuo; Abiko, Yoshimitsu; Yamamoto, Masafumi

    2003-12-12

    In this study, we have assessed the efficacy of the 40-kDa outer membrane protein (40k-OMP) of Porphyromonas gingivalis as a nasal vaccine for the prevention of adult periodontitis. Mice nasally immunized with 40k-OMP and cholera toxin as mucosal adjuvant displayed significant levels of 40k-OMP-specific serum IgG1, IgG2b and IgA as well as mucosal IgA antibodies (Abs) in saliva and nasal secretions. Ab-forming cell (AFC) analysis confirmed the antibody titers by detecting high numbers of 40k-OMP-specific AFCs in spleen, salivary glands and nasal passages. Because 40k-OMP-specific IgG inhibited coaggregation of P. gingivalis vesicles and S. gordonii, it may be an important tool for the prevention of adult periodontitis.

  17. [Endoscopic treatment of small osteoma of nasal sinuses manifested as nasal and facial pain].

    PubMed

    Li, Yu; Zheng, Tianqi; Li, Zhong; Deng, Hongyuan; Guo, Chaoxian

    2015-12-01

    To discuss the clinical features, diagnosis and endoscopic surgical intervention for small steoma of nasal sinuses causing nasal and facial pain. A retrospective review was performed on 21 patients with nasal and facial pain caused by small osteoma of nasal sinuses, and nasal endoscopic surgery was included in the treatment of all cases. The nasal and facial pain of all the patients was relieved. Except for one ase exhibiting periorbital bruise after operation, the other patients showed no postoperative complications. Nasal and facial pain caused by small osteoma of nasal sinuses was clinically rare, mostly due to the neuropathic pain of nose and face caused by local compression resulting from the expansion of osteoma. Early diagnosis and operative treatment can significantly relieve nasal and facial pain.

  18. Oxymetazoline Nasal Spray

    MedlinePlus

    ... is recommended by a doctor. Children 6 to 12 years of age should use oxymetazoline nasal spray carefully and under adult supervision. Oxymetazoline is in a class of medications called nasal decongestants. It works by narrowing the blood vessels in the nasal passages.

  19. Validation of polyvinylidene fluoride nasal sensor to assess nasal obstruction in comparison with subjective technique.

    PubMed

    Roopa Manjunatha, G; Mahapatra, D Roy; Prakash, Surya; Rajanna, K

    2015-01-01

    The aim of this study is to validate the applicability of the PolyVinyliDene Fluoride (PVDF) nasal sensor to assess the nasal airflow, in healthy subjects and patients with nasal obstruction and to correlate the results with the score of Visual Analogue Scale (VAS). PVDF nasal sensor and VAS measurements were carried out in 50 subjects (25-healthy subjects and 25 patients). The VAS score of nasal obstruction and peak-to-peak amplitude (Vp-p) of nasal cycle measured by PVDF nasal sensors were analyzed for right nostril (RN) and left nostril (LN) in both the groups. Spearman's rho correlation was calculated. The relationship between PVDF nasal sensor measurements and severity of nasal obstruction (VAS score) were assessed by ANOVA. In healthy group, the measurement of nasal airflow by PVDF nasal sensor for RN and LN were found to be 51.14±5.87% and 48.85±5.87%, respectively. In patient group, PVDF nasal sensor indicated lesser nasal airflow in the blocked nostrils (RN: 23.33±10.54% and LN: 32.24±11.54%). Moderate correlation was observed in healthy group (r=-0.710, p<0.001 for RN and r=-0.651, p<0.001 for LN), and moderate to strong correlation in patient group (r=-0.751, p<0.01 for RN and r=-0.885, p<0.0001 for LN). PVDF nasal sensor method is a newly developed technique for measuring the nasal airflow. Moderate to strong correlation was observed between PVDF nasal sensor data and VAS scores for nasal obstruction. In our present study, PVDF nasal sensor technique successfully differentiated between healthy subjects and patients with nasal obstruction. Additionally, it can also assess severity of nasal obstruction in comparison with VAS. Thus, we propose that the PVDF nasal sensor technique could be used as a new diagnostic method to evaluate nasal obstruction in routine clinical practice. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Does cost-effectiveness of influenza vaccine choice vary across the U.S.? An agent-based modeling study.

    PubMed

    DePasse, Jay V; Nowalk, Mary Patricia; Smith, Kenneth J; Raviotta, Jonathan M; Shim, Eunha; Zimmerman, Richard K; Brown, Shawn T

    2017-07-13

    In a prior agent-based modeling study, offering a choice of influenza vaccine type was shown to be cost-effective when the simulated population represented the large, Washington DC metropolitan area. This study calculated the public health impact and cost-effectiveness of the same four strategies: No Choice, Pediatric Choice, Adult Choice, or Choice for Both Age Groups in five United States (U.S.) counties selected to represent extremes in population age distribution. The choice offered was either inactivated influenza vaccine delivered intramuscularly with a needle (IIV-IM) or an age-appropriate needle-sparing vaccine, specifically, the nasal spray (LAIV) or intradermal (IIV-ID) delivery system. Using agent-based modeling, individuals were simulated as they interacted with others, and influenza was tracked as it spread through each population. Influenza vaccination coverage derived from Centers for Disease Control and Prevention (CDC) data, was increased by 6.5% (range 3.25%-11.25%) to reflect the effects of vaccine choice. Assuming moderate influenza infectivity, the number of averted cases was highest for the Choice for Both Age Groups in all five counties despite differing demographic profiles. In a cost-effectiveness analysis, Choice for Both Age Groups was the dominant strategy. Sensitivity analyses varying influenza infectivity, costs, and degrees of vaccine coverage increase due to choice, supported the base case findings. Offering a choice to receive a needle-sparing influenza vaccine has the potential to significantly reduce influenza disease burden and to be cost saving. Consistent findings across diverse populations confirmed these findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Cost of goods sold and total cost of delivery for oral and parenteral vaccine packaging formats.

    PubMed

    Sedita, Jeff; Perrella, Stefanie; Morio, Matt; Berbari, Michael; Hsu, Jui-Shan; Saxon, Eugene; Jarrahian, Courtney; Rein-Weston, Annie; Zehrung, Darin

    2018-03-14

    Despite limitations of glass packaging for vaccines, the industry has been slow to implement alternative formats. Polymer containers may address many of these limitations, such as breakage and delamination. However, the ability of polymer containers to achieve cost of goods sold (COGS) and total cost of delivery (TCOD) competitive with that of glass containers is unclear, especially for cost-sensitive low- and lower-middle-income countries. COGS and TCOD models for oral and parenteral vaccine packaging formats were developed based on information from subject matter experts, published literature, and Kenya's comprehensive multiyear plan for immunization. Rotavirus and inactivated poliovirus vaccines (IPV) were used as representative examples of oral and parenteral vaccines, respectively. Packaging technologies evaluated included glass vials, blow-fill-seal (BFS) containers, preformed polymer containers, and compact prefilled auto-disable (CPAD) devices in both BFS and preformed formats. For oral vaccine packaging, BFS multi-monodose (MMD) ampoules were the least expensive format, with a COGS of $0.12 per dose. In comparison, oral single-dose glass vials had a COGS of $0.40. BFS MMD ampoules had the lowest TCOD of oral vaccine containers at $1.19 per dose delivered, and ten-dose glass vials had a TCOD of $1.61 per dose delivered. For parenteral vaccines, the lowest COGS was achieved with ten-dose glass vials at $0.22 per dose. In contrast, preformed CPAD devices had the highest COGS at $0.60 per dose. Ten-dose glass vials achieved the lowest TCOD of the parenteral vaccine formats at $1.56 per dose delivered. Of the polymer containers for parenteral vaccines, BFS MMD ampoules achieved the lowest TCOD at $1.89 per dose delivered, whereas preformed CPAD devices remained the most expensive format, at $2.25 per dose delivered. Given their potential to address the limitations of glass and reduce COGS and TCOD, polymer containers deserve further consideration as alternative

  2. Novel vaccine development strategies for inducing mucosal immunity

    PubMed Central

    Fujkuyama, Yoshiko; Tokuhara, Daisuke; Kataoka, Kosuke; Gilbert, Rebekah S; McGhee, Jerry R; Yuki, Yoshikazu; Kiyono, Hiroshi; Fujihashi, Kohtaro

    2012-01-01

    To develop protective immune responses against mucosal pathogens, the delivery route and adjuvants for vaccination are important. The host, however, strives to maintain mucosal homeostasis by responding to mucosal antigens with tolerance, instead of immune activation. Thus, induction of mucosal immunity through vaccination is a rather difficult task, and potent mucosal adjuvants, vectors or other special delivery systems are often used, especially in the elderly. By taking advantage of the common mucosal immune system, the targeting of mucosal dendritic cells and microfold epithelial cells may facilitate the induction of effective mucosal immunity. Thus, novel routes of immunization and antigen delivery systems also show great potential for the development of effective and safe mucosal vaccines against various pathogens. The purpose of this review is to introduce several recent approaches to induce mucosal immunity to vaccines, with an emphasis on mucosal tissue targeting, new immunization routes and delivery systems. Defining the mechanisms of mucosal vaccines is as important as their efficacy and safety, and in this article, examples of recent approaches, which will likely accelerate progress in mucosal vaccine development, are discussed. PMID:22380827

  3. Microneedle-based vaccines

    PubMed Central

    Prausnitz, Mark R.; Mikszta, John A.; Cormier, Michel; Andrianov, Alexander K.

    2010-01-01

    The threat of pandemic influenza and other public health needs motivates development of better vaccine delivery systems. To address this need, microneedles have been developed as micron-scale needles fabricated using low-cost manufacturing methods that administer vaccine into the skin using a simple device that may be suitable for self-administration. Delivery using solid or hollow microneedles can be accomplished by (i) piercing the skin and then applying a vaccine formulation or patch onto the permeabilized skin, (ii) coating or encapsulating vaccine onto or within microneedles for rapid, or delayed, dissolution and release in the skin and (iii) injection into the skin using a modified syringe or pump. Extensive clinical experience with smallpox, TB and other vaccines has shown that vaccine delivery into the skin using conventional intradermal injection is generally safe and effective and often elicits the same immune responses at lower doses compared to intramuscular injection. Animal experiments using microneedles have shown similar benefits. Microneedles have been used to deliver whole, inactivated virus; trivalent split antigen vaccines; and DNA plasmid encoding the influenza hemagglutinin to rodents and found strong antibody responses. In addition, ChimeriVax™-JE against yellow fever was administered to non-human primates and generated protective levels of neutralizing antibodies more than seven times greater than subcutaneous delivery; DNA plasmid encoding hepatitis B surface antigen was administered to mice and generated antibody and T cell responses at least as strong as hypodermic injections; recombinant Protective Antigen of Baccilus anthracis was administered to rabbits and provided complete protection from lethal aerosol anthrax spore challenge at a lower dose than intramuscular injection; and DNA plasmid encoding four vaccinia virus genes administered to mice in combination with electroporation generated neutralizing antibodies that apparently

  4. Correlation of Nasal Mucosal Temperature With Subjective Nasal Patency in Healthy Individuals.

    PubMed

    Bailey, Ryan S; Casey, Kevin P; Pawar, Sachin S; Garcia, Guilherme J M

    2017-01-01

    Historically, otolaryngologists have focused on nasal resistance to airflow and minimum airspace cross-sectional area as objective measures of nasal obstruction using methods such as rhinomanometry and acoustic rhinometry. However, subjective sensation of nasal patency may be more associated with activation of cold receptors by inspired air than with respiratory effort. To investigate whether subjective nasal patency correlates with nasal mucosal temperature in healthy individuals. Healthy adult volunteers first completed the Nasal Obstruction Symptom Evaluation (NOSE) and a unilateral visual analog scale to quantify subjective nasal patency. A miniaturized thermocouple sensor was then used to record nasal mucosal temperature bilaterally in 2 locations along the nasal septum: at the vestibule and across from the inferior turbinate head. Nasal mucosal temperature and subjective patency scores in healthy individuals. The 22 healthy adult volunteers (12 [55%] male; mean [SD] age, 28.3 [7.0] years) had a mean (SD) NOSE score of 5.9 (8.4) (range, 0-30) and unilateral VAS score of 1.2 (1.4) (range, 0-5). The range of temperature oscillations during the breathing cycle, defined as the difference between end-expiratory and end-inspiratory temperatures, was greater during deep breaths (mean [SD] change in temperature, 6.2°C [2.6°C]) than during resting breathing (mean [SD] change in temperature, 4.2°C [2.3°C]) in both locations (P < .001). Mucosal temperature measured at the right vestibule had a statistically significant correlation with both right-side visual analog scale score (Pearson r = -0.55; 95% CI, -0.79 to -0.17; P = .008) and NOSE score (Pearson r = -0.47; 95% CI, -0.74 to -0.06; P = .03). No other statistically significant correlations were found between mucosal temperature and subjective nasal patency scores. Nasal mucosal temperature was lower (mean of 1.5°C lower) in the first cavity to be measured, which was the right cavity in all

  5. Biomimetic design in microparticulate vaccines.

    PubMed

    Keegan, Mark E; Whittum-Hudson, Judith A; Mark Saltzman, W

    2003-11-01

    Current efforts to improve the effectiveness of microparticle vaccines include incorporating biomimetic features into the particles. Many pathogens use surface molecules to target specific cell types in the gut for host invasion. This observation has inspired efforts to chemically conjugate cell-type targeting ligands to the surfaces of microparticles in order to increase the efficiency of uptake, and therefore the effectiveness, of orally administered microparticles. Bio-mimicry is not limited to the exterior surface of the microparticles. Anti-idiotypic antibodies, cytokines or other biological modifiers can be encapsulated for delivery to sites of interest as vaccines or other therapeutics. Direct mucosal delivery of microparticle vaccines or immunomodulatory agents may profoundly enhance mucosal and systemic immune responses compared to other delivery routes.

  6. Oral poliovirus vaccination and pregnancy complications.

    PubMed

    Harjulehto-Mervaala, T; Hovi, T; Aro, T; Saxén, H; Hiilesmaa, V K

    1995-04-01

    To determine whether the effect of live attenuated oral polio virus vaccine given to pregnant women increases pregnancy complications. A study of women who had been vaccinated against poliovirus during a national vaccination campaign and who had delivered by cesarean section in three obstetrical hospitals in southern Finland. One thousand seven hundred and forty-seven vaccinated women (in three study cohorts), and their 2293 nonvaccinated controls (in two reference cohorts) were analyzed. Subjects are out of 22,000 deliveries evaluated earlier. Vaccinated sectioned women did not show an excess of pregnancy complications. The mean rate of cesarean sections was 18.4% in the study cohorts and 18.9% in the reference cohorts counted from the 22,000 deliveries. Oral live attenuated polio virus vaccine does not increase pregnancy complications and is considered a safe alternative for vaccinating pregnant women.

  7. [Dexpanthenol nasal spray in comparison to dexpanthenol nasal ointment. A prospective, randomised, open, cross-over study to compare nasal mucociliary clearance].

    PubMed

    Verse, T; Klöcker, N; Riedel, F; Pirsig, W; Scheithauer, M O

    2004-07-01

    Recent technical developments in metered pump systems allow the production and use of preservative-free nasal products. The aim of the current study is to compare the tolerability of a preservative-free dexpanthenol (5%) nasal spray with that of the established dexpanthenol (5%) nasal ointment, also without preservatives. The main outcome measure was in vivo mucociliary clearance. Mucociliary clearance was assessed by saccharin migration time in 20 volunteers. Wash-out phases were 7 days and the spray or ointment was always applied 20 min before the saccharin test. The study was designed to test for non-inferiority. Saccharin migration time was slightly longer after ointment administration, however, these were not significantly different to nasal spray. The saccharin migration time showed a significant correlation with the age of the volunteers. The upper confidence limit of dexpanthenol nasal spray was markedly less than that of the ointment. Therefore, dexpanthenol nasal spray is at least equal to if not better than dexpanthenol nasal ointment. Due to its ease of administration, preservative-free dexpanthenol nasal spray offers a valuable therapeutic alternative.

  8. Development of an Acid-Resistant Salmonella Typhi Ty21a Attenuated Vector For Improved Oral Vaccine Delivery.

    PubMed

    Dharmasena, Madushini N; Feuille, Catherine M; Starke, Carly Elizabeth C; Bhagwat, Arvind A; Stibitz, Scott; Kopecko, Dennis J

    The licensed oral, live-attenuated bacterial vaccine for typhoid fever, Salmonella enterica serovar Typhi strain Ty21a, has also been utilized as a vaccine delivery platform for expression of diverse foreign antigens that stimulate protection against shigellosis, anthrax, plague, or human papilloma virus. However, Ty21a is acid-labile and, for effective oral immunization, stomach acidity has to be either neutralized with buffer or by-passed with Ty21a in an enteric-coated capsule (ECC). Several studies have shown that efficacy is reduced when Ty21a is administered in an ECC versus as a buffered liquid formulation, the former limiting exposure to GI tract lymphoid tissues. However, the ECC was selected as a more practical delivery format for both packaging/shipping and vaccine administration ease. We have sought to increase Ty21a acid-resistance to allow for removal from the ECC and immune enhancement. To improve Ty21a acid-resistance, glutamate-dependent acid resistance genes (GAD; responsible for Shigella spp. survival at very low pH) were cloned on a multi-copy plasmid (pGad) under a controllable arabinose-inducible promoter. pGad enhanced acid survival of Ty21a by 5 logs after 3 hours at pH 2.5, when cells were pre-grown in arabinose and under conditions that promote an acid-tolerance response (ATR). For genetically 100% stable expression, we inserted the gad genes into the Ty21a chromosome, using a method that allowed for subsequent removal of a selectable antibiotic resistance marker. Further, both bacterial growth curves and survival assays in cultured human monocytes/macrophages suggest that neither the genetic methods employed nor the resulting acid-resistance conferred by expression of the Gad proteins in Ty21a had any effect on the existing attenuation of this vaccine strain.

  9. Mass Vaccination with a New, Less Expensive Oral Cholera Vaccine Using Public Health Infrastructure in India: The Odisha Model

    PubMed Central

    Kar, Shantanu K.; Sah, Binod; Patnaik, Bikash; Kim, Yang Hee; Kerketta, Anna S.; Shin, Sunheang; Rath, Shyam Bandhu; Ali, Mohammad; Mogasale, Vittal; Khuntia, Hemant K.; Bhattachan, Anuj; You, Young Ae; Puri, Mahesh K.; Lopez, Anna Lena; Maskery, Brian; Nair, Gopinath B.; Clemens, John D.; Wierzba, Thomas F.

    2014-01-01

    Introduction The substantial morbidity and mortality associated with recent cholera outbreaks in Haiti and Zimbabwe, as well as with cholera endemicity in countries throughout Asia and Africa, make a compelling case for supplementary cholera control measures in addition to existing interventions. Clinical trials conducted in Kolkata, India, have led to World Health Organization (WHO)-prequalification of Shanchol, an oral cholera vaccine (OCV) with a demonstrated 65% efficacy at 5 years post-vaccination. However, before this vaccine is widely used in endemic areas or in areas at risk of outbreaks, as recommended by the WHO, policymakers will require empirical evidence on its implementation and delivery costs in public health programs. The objective of the present report is to describe the organization, vaccine coverage, and delivery costs of mass vaccination with a new, less expensive OCV (Shanchol) using existing public health infrastructure in Odisha, India, as a model. Methods All healthy, non-pregnant residents aged 1 year and above residing in selected villages of the Satyabadi block (Puri district, Odisha, India) were invited to participate in a mass vaccination campaign using two doses of OCV. Prior to the campaign, a de jure census, micro-planning for vaccination and social mobilization activities were implemented. Vaccine coverage for each dose was ascertained as a percentage of the censused population. The direct vaccine delivery costs were estimated by reviewing project expenditure records and by interviewing key personnel. Results The mass vaccination was conducted during May and June, 2011, in two phases. In each phase, two vaccine doses were given 14 days apart. Sixty-two vaccination booths, staffed by 395 health workers/volunteers, were established in the community. For the censused population, 31,552 persons (61% of the target population) received the first dose and 23,751 (46%) of these completed their second dose, with a drop-out rate of 25

  10. Mass vaccination with a new, less expensive oral cholera vaccine using public health infrastructure in India: the Odisha model.

    PubMed

    Kar, Shantanu K; Sah, Binod; Patnaik, Bikash; Kim, Yang Hee; Kerketta, Anna S; Shin, Sunheang; Rath, Shyam Bandhu; Ali, Mohammad; Mogasale, Vittal; Khuntia, Hemant K; Bhattachan, Anuj; You, Young Ae; Puri, Mahesh K; Lopez, Anna Lena; Maskery, Brian; Nair, Gopinath B; Clemens, John D; Wierzba, Thomas F

    2014-02-01

    The substantial morbidity and mortality associated with recent cholera outbreaks in Haiti and Zimbabwe, as well as with cholera endemicity in countries throughout Asia and Africa, make a compelling case for supplementary cholera control measures in addition to existing interventions. Clinical trials conducted in Kolkata, India, have led to World Health Organization (WHO)-prequalification of Shanchol, an oral cholera vaccine (OCV) with a demonstrated 65% efficacy at 5 years post-vaccination. However, before this vaccine is widely used in endemic areas or in areas at risk of outbreaks, as recommended by the WHO, policymakers will require empirical evidence on its implementation and delivery costs in public health programs. The objective of the present report is to describe the organization, vaccine coverage, and delivery costs of mass vaccination with a new, less expensive OCV (Shanchol) using existing public health infrastructure in Odisha, India, as a model. All healthy, non-pregnant residents aged 1 year and above residing in selected villages of the Satyabadi block (Puri district, Odisha, India) were invited to participate in a mass vaccination campaign using two doses of OCV. Prior to the campaign, a de jure census, micro-planning for vaccination and social mobilization activities were implemented. Vaccine coverage for each dose was ascertained as a percentage of the censused population. The direct vaccine delivery costs were estimated by reviewing project expenditure records and by interviewing key personnel. The mass vaccination was conducted during May and June, 2011, in two phases. In each phase, two vaccine doses were given 14 days apart. Sixty-two vaccination booths, staffed by 395 health workers/volunteers, were established in the community. For the censused population, 31,552 persons (61% of the target population) received the first dose and 23,751 (46%) of these completed their second dose, with a drop-out rate of 25% between the two doses. Higher

  11. Nasal Cancer

    MedlinePlus

    ... the way to your throat as you breathe. Cancer of the nasal cavity and paranasal sinuses is ... be like those of infections. Doctors diagnose nasal cancer with imaging tests, lighted tube-like instruments that ...

  12. Supplemental oxygen: ensuring its safe delivery during facial surgery.

    PubMed

    Reyes, R J; Smith, A A; Mascaro, J R; Windle, B H

    1995-04-01

    Electrosurgical coagulation in the presence of blow-by oxygen is a potential source of fire in facial surgery. A case report of a patient sustaining partial-thickness facial burns secondary to such a flash fire is presented. A fiberglass facial model is then used to study the variables involved in providing supplemental oxygen when an electrosurgical unit is employed. Oxygen flow, oxygen delivery systems, distance from the oxygen source, and coagulation current levels were varied. A nasal cannula and an adapted suction tubing provided the oxygen delivery systems on the model. Both the "displaced" nasal cannula and the adapted suction tubing ignited at a minimum coagulation level of 30 W, an oxygen flow of 2 liters/minute, and a linear distance of 5 cm from the oxygen source. The properly placed nasal cannula did not ignite at any combination of oxygen flow, coagulation current level, or distance from the oxygen source. Facial cutaneous surgery in patients provided supplemental oxygen should be practiced with caution when an electrosurgical unit is used for coagulation. The oxygen delivery systems adapted for use are hazardous and should not be used until their safety has been demonstrated.

  13. Nasal Physiology

    MedlinePlus

    ... Anatomy Virtual Anatomy Disclosure Statement Printer Friendly Nasal Physiology Jeremiah A. Alt, MD, PhD Noam Cohen, MD, ... control the inflammation. CONCLUSION An understanding of the physiology of the nose is critical to understand nasal ...

  14. Measles Vaccine.

    PubMed

    Griffin, Diane E

    2018-03-01

    Measles remains an important cause of child morbidity and mortality worldwide despite the availability of a safe and efficacious vaccine. The current measles virus (MeV) vaccine was developed empirically by attenuation of wild-type (WT) MeV by in vitro passage in human and chicken cells and licensed in 1963. Additional passages led to further attenuation and the successful vaccine strains in widespread use today. Attenuation is associated with decreased replication in lymphoid tissue, but the molecular basis for this restriction has not been identified. The immune response is age dependent, inhibited by maternal antibody (Ab) and involves induction of both Ab and T cell responses that resemble the responses to WT MeV infection, but are lower in magnitude. Protective immunity is correlated with levels of neutralizing Ab, but the actual immunologic determinants of protection are not known. Because measles is highly transmissible, control requires high levels of population immunity. Delivery of the two doses of vaccine needed to achieve >90% immunity is accomplished by routine immunization of infants at 9-15 months of age followed by a second dose delivered before school entry or by periodic mass vaccination campaigns. Because delivery by injection creates hurdles to sustained high coverage, there are efforts to deliver MeV vaccine by inhalation. In addition, the safety record for the vaccine combined with advances in reverse genetics for negative strand viruses has expanded proposed uses for recombinant versions of measles vaccine as vectors for immunization against other infections and as oncolytic agents for a variety of tumors.

  15. Assessment of nasal spray deposition pattern in a silicone human nose model using a color-based method.

    PubMed

    Kundoor, Vipra; Dalby, Richard N

    2010-01-01

    To develop a simple and inexpensive method to visualize and quantify droplet deposition patterns. Deposition pattern was determined by uniformly coating the nose model with Sar-Gel (a paste that changes from white to purple on contact with water) and subsequently discharging sprays into the nose model. The color change was captured using a digital camera and analyzed using Adobe Photoshop. Several tests were conducted to validate the method. Deposition patterns of different nasal sprays (Ayr, Afrin, and Zicam) and different nasal drug delivery devices (Afrin nasal spray and PARI Sinustar nasal nebulizer) were compared. We also used the method to evaluate the effect of inhaled flow rate on nasal spray deposition. There was a significant difference in the deposition area for Ayr, Afrin, and Zicam. The deposition areas of Afrin nasal spray and PARI Sinustar nasal nebulizer (2 min and 5 min) were significantly different. Inhaled flow rate did not have a significant effect on the deposition pattern. Lower viscosity formulations (Ayr, Afrin) provided greater coverage than the higher viscosity formulation (Zicam). The nebulizer covered a greater surface area than the spray pump we evaluated. Aerosol deposition in the nose model was not affected by air flow conditions.

  16. A microarray MEMS device for biolistic delivery of vaccine and drug powders.

    PubMed

    Pirmoradi, Fatemeh Nazly; Pattekar, Ashish V; Linn, Felicia; Recht, Michael I; Volkel, Armin R; Wang, Qian; Anderson, Greg B; Veiseh, Mandana; Kjono, Sandra; Peeters, Eric; Uhland, Scott A; Chow, Eugene M

    2015-01-01

    We report a biolistic technology platform for physical delivery of particle formulations of drugs or vaccines using parallel arrays of microchannels, which generate highly collimated jets of particles with high spatial resolution. Our approach allows for effective delivery of therapeutics sequentially or concurrently (in mixture) at a specified target location or treatment area. We show this new platform enables the delivery of a broad range of particles with various densities and sizes into both in vitro and ex vivo skin models. Penetration depths of ∼1 mm have been achieved following a single ejection of 200 µg high-density gold particles, as well as 13.6 µg low-density polystyrene-based particles into gelatin-based skin simulants at 70 psi inlet gas pressure. Ejection of multiple shots at one treatment site enabled deeper penetration of ∼3 mm in vitro, and delivery of a higher dose of 1 mg gold particles at similar inlet gas pressure. We demonstrate that particle penetration depths can be optimized in vitro by adjusting the inlet pressure of the carrier gas, and dosing is controlled by drug reservoirs that hold precise quantities of the payload, which can be ejected continuously or in pulses. Future investigations include comparison between continuous versus pulsatile payload deliveries. We have successfully delivered plasmid DNA (pDNA)-coated gold particles (1.15 µm diameter) into ex vivo murine and porcine skin at low inlet pressures of ∼30 psi. Integrity analysis of these pDNA-coated gold particles confirmed the preservation of full-length pDNA after each particle preparation and jetting procedures. This technology platform provides distinct capabilities to effectively deliver a broad range of particle formulations into skin with specially designed high-speed microarray ejector nozzles.

  17. A microarray MEMS device for biolistic delivery of vaccine and drug powders

    PubMed Central

    Pirmoradi, Fatemeh Nazly; Pattekar, Ashish V; Linn, Felicia; Recht, Michael I; Volkel, Armin R; Wang, Qian; Anderson, Greg B; Veiseh, Mandana; Kjono, Sandra; Peeters, Eric; Uhland, Scott A; Chow, Eugene M

    2015-01-01

    We report a biolistic technology platform for physical delivery of particle formulations of drugs or vaccines using parallel arrays of microchannels, which generate highly collimated jets of particles with high spatial resolution. Our approach allows for effective delivery of therapeutics sequentially or concurrently (in mixture) at a specified target location or treatment area. We show this new platform enables the delivery of a broad range of particles with various densities and sizes into both in vitro and ex vivo skin models. Penetration depths of ∼1 mm have been achieved following a single ejection of 200 µg high-density gold particles, as well as 13.6 µg low-density polystyrene-based particles into gelatin-based skin simulants at 70 psi inlet gas pressure. Ejection of multiple shots at one treatment site enabled deeper penetration of ∼3 mm in vitro, and delivery of a higher dose of 1 mg gold particles at similar inlet gas pressure. We demonstrate that particle penetration depths can be optimized in vitro by adjusting the inlet pressure of the carrier gas, and dosing is controlled by drug reservoirs that hold precise quantities of the payload, which can be ejected continuously or in pulses. Future investigations include comparison between continuous versus pulsatile payload deliveries. We have successfully delivered plasmid DNA (pDNA)-coated gold particles (1.15 µm diameter) into ex vivo murine and porcine skin at low inlet pressures of ∼30 psi. Integrity analysis of these pDNA-coated gold particles confirmed the preservation of full-length pDNA after each particle preparation and jetting procedures. This technology platform provides distinct capabilities to effectively deliver a broad range of particle formulations into skin with specially designed high-speed microarray ejector nozzles. PMID:26090875

  18. Vaccines against human diarrheal pathogens

    PubMed Central

    Böhles, Nathalie; Böhles, Nathalie; Busch, Kim; Busch, Kim; Hensel, Michael; Hensel, Michael

    2014-01-01

    Worldwide, nearly 1.7 billion people per year contract diarrheal infectious diseases (DID) and almost 760 000 of infections are fatal. DID are a major problem in developing countries where poor sanitation prevails and food and water may become contaminated by fecal shedding. Diarrhea is caused by pathogens such as bacteria, protozoans and viruses. Important diarrheal pathogens are Vibrio cholerae, Shigella spp. and rotavirus, which can be prevented with vaccines for several years. The focus of this review is on currently available vaccines against these three pathogens, and on development of new vaccines. Currently, various types of vaccines based on traditional (killed, live attenuated, toxoid or conjugate vaccines) and reverse vaccinology (DNA/mRNA, vector, recombinant subunit, plant vaccines) are in development or already available. Development of new vaccines demands high levels of knowledge, experience, budget, and time, yet promising new vaccines often fail in preclinical and clinical studies. Efficacy of vaccination also depends on the route of delivery, and mucosal immunization in particular is of special interest for preventing DID. Furthermore, adjuvants, delivery systems and other vaccine components are essential for an adequate immune response. These aspects will be discussed in relation to the improvement of existing and development of new vaccines against DID. PMID:24861668

  19. Home delivery of heat-stable vaccines in Indonesia: outreach immunization with a prefilled, single-use injection device.

    PubMed Central

    Sutanto, A.; Suarnawa, I. M.; Nelson, C. M.; Stewart, T.; Soewarso, T. I.

    1999-01-01

    Extending immunization coverage to underserved populations will require innovative immunization strategies. This study evaluated one such strategy: the use of a prefilled, single-use injection device for outreach immunization by village midwives. The device, UniJect, is designed to prevent refilling or reuse. Stored at ambient temperatures for up to 1 month in midwives' homes, vaccine-filled UniJect devices were immediately available for outreach. Between July 1995 and April 1996, 110 midwives on the Indonesia islands of Lombok and Bali visited the homes of newborn infants to deliver hepatitis B vaccine to the infants and tetanus toxoid to their mothers. Observations and interviews showed that the midwives used the device properly and safely to administer approximately 10,000 sterile injections in home settings. There were no problems with excessive heat exposure during the storage or delivery of vaccine. Injection recipients and midwives expressed a strong preference for the UniJect device over a standard syringe. Use of the prefilled device outside the cold chain simplified the logistics and facilitated the speed and efficiency of home visits, while the single-dose format minimized vaccine wastage. PMID:10083709

  20. Nasal computed tomography.

    PubMed

    Kuehn, Ned F

    2006-05-01

    Chronic nasal disease is often a challenge to diagnose. Computed tomography greatly enhances the ability to diagnose chronic nasal disease in dogs and cats. Nasal computed tomography provides detailed information regarding the extent of disease, accurate discrimination of neoplastic versus nonneoplastic diseases, and identification of areas of the nose to examine rhinoscopically and suspicious regions to target for biopsy.

  1. Comparative performance of public and private sector delivery of BCG vaccination: evidence from Sub-Saharan Africa.

    PubMed

    Wagner, Zachary; Szilagyi, Peter G; Sood, Neeraj

    2014-07-31

    The private sector is an important source of health care in the developing world. However, there is limited evidence on how private providers compare to public providers, particularly for preventive services such as immunizations. We used data from Sub-Saharan Africa (SSA) to assess public-private differences in Bacillus Calmette-Guérin (BCG) vaccine delivery. We used demographic and health surveys from 102,629 children aged 0-59 months from 29 countries across SSA to measure differences in BCG status for children born at private versus public health facilities (BCG is recommended at birth). We used a probit model to estimate public-private differences in BCG delivery, while controlling for key confounders. Next, we estimated how differences in BCG status evolved over time for children born at private versus public facilities. Finally, we estimated heterogeneity in public-private differences based on wealth and rural-urban residency. We found that children born at a private facility were 7.1 percentage points less likely to receive BCG vaccine in the same month as birth than children born at a public facility (95% CI 6.3-8.0; p<0.001). Most of this difference was driven by for-profit private providers (as opposed to NGOs) where the BCG provision rate was 10.0 percentage points less than public providers (95% CI 9.0-11.2; p<0.001) compared to only 2.4 percentage points for NGOs (95% CI 1.0-3. 8; p<0.01). Moreover, children born at private for-profit facilities remained less likely to be vaccinated up to 59 months after birth. Finally, public-private differences were more pronounced for poorer children and children in rural areas. The for-profit private sector performed substantially worse than the public sector in providing BCG vaccine to newborns, resulting in a longer duration of vulnerability to tuberculosis. This disparity was greater for poorer children and children in rural areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Re-designing the Mozambique vaccine supply chain to improve access to vaccines.

    PubMed

    Lee, Bruce Y; Haidari, Leila A; Prosser, Wendy; Connor, Diana L; Bechtel, Ruth; Dipuve, Amelia; Kassim, Hidayat; Khanlawia, Balbina; Brown, Shawn T

    2016-09-22

    Populations and routine childhood vaccine regimens have changed substantially since supply chains were designed in the 1980s, and introducing new vaccines during the "Decade of Vaccine" may exacerbate existing bottlenecks, further inhibiting the flow of all vaccines. Working with the Mozambique Ministry of Health, our team implemented a new process that integrated HERMES computational simulation modeling and on-the-ground implementers to evaluate and improve the Mozambique vaccine supply chain using a system-re-design that integrated new supply chain structures, information technology, equipment, personnel, and policies. The alternative system design raised vaccine availability (from 66% to 93% in Gaza; from 76% to 84% in Cabo Delgado) and reduced the logistics cost per dose administered (from $0.53 to $0.32 in Gaza; from $0.38 to $0.24 in Cabo Delgado) as compared to the multi-tiered system under the current EPI. The alternative system also produced higher availability at lower costs after new vaccine introductions. Since reviewing scenarios modeling deliveries every two months in the north of Gaza, the provincial directorate has decided to pilot this approach diverging from decades of policies dictating monthly deliveries. Re-design improved not only supply chain efficacy but also efficiency, important since resources to deliver vaccines are limited. The Mozambique experience and process can serve as a model for other countries during the Decade of Vaccines. For the Decade of Vaccines, getting vaccines at affordable prices to the market is not enough. Vaccines must reach the population to be successful. Copyright © 2016. Published by Elsevier Ltd.

  3. A paradigm for peptide vaccine delivery using viral epitopes encapsulated in degradable polymer hydrogel capsules.

    PubMed

    Chong, Siow-Feng; Sexton, Amy; De Rose, Robert; Kent, Stephen J; Zelikin, Alexander N; Caruso, Frank

    2009-10-01

    We report on the use of degradable polymer capsules as carriers for the delivery of oligopeptide antigens to professional antigen presenting cells (APCs). To achieve encapsulation, oligopeptide sequences were covalently linked to a negatively charged carrier polymer via biodegradable linkages and the resulting conjugate was then adsorbed onto amine-functionalized silica particles. These peptide-coated particles were then used as templates for the layer-by-layer (LbL) deposition of thiolated poly(methacrylic acid) (PMA(SH)) and poly(vinylpyrrolidone) (PVPON) multilayers. Removal of the silica core and disruption of the hydrogen bonding between PMA(SH) and PVPON by altering the solution pH yielded disulfide-stabilized PMA capsules that retain the encapsulated cargo in an oxidative environment. In the presence of a natural reducing agent, glutathione, cleavage of the disulfide bonds causes release of the peptide from the capsules. The developed strategy provides control over peptide loading into polymer capsules and yields colloidally stable micron- and submicron-sized carriers with uniform size and peptide loading. The conjugation and encapsulation procedures were proven to be non-degrading to the peptide vaccines. The peptide-loaded capsules were successfully used to deliver their cargo to APCs and activate CD8 T lymphocytes in a non-human primate model of SIV infection ex vivo. The reported approach represents a novel paradigm in the delivery of peptide vaccines and other therapeutic agents.

  4. Perception of Better Nasal Patency Correlates with Increased Mucosal Cooling after Surgery for Nasal Obstruction

    NASA Astrophysics Data System (ADS)

    Garcia, Guilherme; Sullivan, Corbin; Frank-Ito, Dennis; Kimbell, Julia; Rhee, John

    2014-11-01

    Nasal airway obstruction (NAO) is a common health problem with 340,000 patients undergoing surgery annually in the United States. Traditionally, otolaryngologists have focused on airspace cross-sectional areas and nasal resistance to airflow as objective measures of nasal patency, but neither of these variables correlated consistently with patients' symptoms. Given that the sensation of nasal airflow is also associated with mucosal cooling (i.e., heat loss) during inspiration, we investigated the correlation between the sensation of nasal obstruction and mucosal cooling in 10 patients before and after NAO surgery. Three-dimensional models of the nasal anatomy were created based on pre- and post-surgery computed tomography scans. Computational fluid dynamics (CFD) simulations were conducted to quantify nasal resistance and mucosal cooling. Patient-reported symptoms were measured by a visual analog scale and the Nasal Obstruction Symptom Evaluation (NOSE), a disease-specific quality of life questionnaire. Our results revealed that the subjective sensation of nasal obstruction correlated with both nasal resistance and heat loss, but the strongest correlation was between the NOSE score and the nasal surface area where heat flux exceeds 50 W /m2 . In conclusion, a significant post-operative increase in mucosal cooling correlates well with patients' perception of better nasal patency after NAO surgery.

  5. Enhanced immunity in intradermal vaccination by novel hollow microneedles.

    PubMed

    Ogai, N; Nonaka, I; Toda, Y; Ono, T; Minegishi, S; Inou, A; Hachiya, M; Fukamizu, H

    2018-04-29

    The intradermal (ID) route for vaccination represents an effective alternative to subcutaneous (SC)/intramuscular administration to induce protective immunity. However, a critical issue associated with ID vaccination is the precise delivery of solution in the upper dermis, which ensures enhanced immunity. We fabricated a hollow microneedle unit made of poly-glycolic acid by injection molding and bonding, and created a dedicated prototype injector. To ensure ID delivery of solution, the injected site was macroscopically and microscopically examined. Serum immunoglobulin G antibody production was measured by enzyme immunoassay and compared in groups of rats following either ID delivery with microneedles or SC administration with a 27-G stainless needle of graded vaccine doses. The unit used a tandem array of six microneedles, each with a side delivery hole, and a conduit inside for solution. Microneedles installed in the injector punctured the skin with the aid of a spring. Injection of solution formed a wheal due to ID distribution. Histologically, a wedge-shaped skin defect in the upper skin corresponded to each puncture site. Antibody titers following vaccinations on days 1 and 8 were significantly higher with ID injection than with SC delivery on day 15 and every 7 days thereafter until day 36 with mumps vaccination, and until day 36 with varicella vaccination. The microneedle unit presented here delivered solution intradermally without any difficulty and evoked antibody responses against viruses even with the reduced vaccine volume. Our findings confirm promising results of ID delivery as an immunogenic option to enhance vaccination efficacy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Bacterial polyester inclusions engineered to display vaccine candidate antigens for use as a novel class of safe and efficient vaccine delivery agents.

    PubMed

    Parlane, Natalie A; Wedlock, D Neil; Buddle, Bryce M; Rehm, Bernd H A

    2009-12-01

    Bioengineered bacterial polyester inclusions have the potential to be used as a vaccine delivery system. The biopolyester beads were engineered to display a fusion protein of the polyester synthase PhaC and the two key antigens involved in immune response to the infectious agent that causes tuberculosis, Mycobacterium tuberculosis, notably antigen 85A (Ag85A) and the 6-kDa early secreted antigenic target (ESAT-6) from Mycobacterium tuberculosis. Polyester beads displaying the respective fusion protein at a high density were successfully produced (henceforth called Ag85A-ESAT-6 beads) by recombinant Escherichia coli. The ability of the Ag85A-ESAT-6 beads to enhance mouse immunity to the displayed antigens was investigated. The beads were not toxic to the animals, as determined by weight gain and absence of lesions at the inoculation site in immunized animals. In vivo injection of the Ag85A-ESAT-6 beads in mice induced significant humoral and cell-mediated immune responses to both Ag85A and ESAT-6. Vaccination with Ag85A-ESAT-6 beads was efficient at stimulating immunity on their own, and this ability was enhanced by administration of the beads in an oil-in-water emulsion. In addition, vaccination with the Ag85A-ESAT-6 beads induced significantly stronger humoral and cell-mediated immune responses than vaccination with an equivalent dose of the fusion protein Ag85A-ESAT-6 alone. The immune response induced by the beads was of a mixed Th1/Th2 nature, as assessed from the induction of the cytokine gamma interferon (Th1 immune response) and increased levels of immunoglobulin G1 (Th2 immune response). Hence, engineered biopolyester beads displaying foreign antigens represent a new class of versatile, safe, and biocompatible vaccines.

  7. [Clinical effects of nasal glucocorticoid on amelioration of nasal obstruction in patients with persistent non-allergic rhinitis].

    PubMed

    Sail, Giyab A; Zuo, Ke-jun; Xu, Geng

    2009-09-01

    To observe the efficacy of nasal glucocorticoid continuously used for 12 weeks on nasal obstruction in patients with persistent non-allergic rhinitis (PNAR). The changes of nasal obstruction, nasal resistance, nasal mucous membrane and quality of life in 47 patients with PNAR were observed. The efficacy of nasal glucocorticoid (Mometasone Furoate Nasal Spray, MFNS 200 microg/day) on patients with PNAR was evaluated. The results of nasal glucocorticoid (MFNS) continuously used for 12 weeks demonstrated: (1) After treatment, the nasal obstruction, nasal discharge, nasal obstruction related dizziness, headache, hyposmia, daily life activity, whole body fatigue, mental status were significantly improved (P < 0.05). (2) Nasal resistance showed significant amelioration (pre-treatment = 0.28 +/- 0.10, post- treatment = 0.16 +/- 0.05; F = 91.471, P < 0.05). (3) SF-36 questionnaire revealed that role physical, bodily pain, general health, role emotional had significant amelioration (P < 0.01). (4) SNOT-20 questionnaire revealed that the defatigation, impaired concentration, pinch the nose, nasal discharging into the throat, sleep quality had significant amelioration (P < 0.01). (5) Continued treatment for 12 weeks was better than 4 weeks, continued treatment had good effect. The study shows that nasal glucocorticoid improved the nasal obstruction, nasal resistance, nasal mucous membrane and quality of life in patients with PNAR.

  8. Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Effects of Nasal Spray Suspension Particle Size and Properties.

    PubMed

    Rygg, Alex; Hindle, Michael; Longest, P Worth

    2016-04-01

    The objective of this study was to use a recently developed nasal dissolution, absorption, and clearance (DAC) model to evaluate the extent to which suspended drug particle size influences nasal epithelial drug absorption for a spray product. Computational fluid dynamics (CFD) simulations of mucociliary clearance and drug dissolution were used to calculate total and microscale epithelial absorption of drug delivered with a nasal spray pump. Ranges of suspended particle sizes, drug solubilities, and partition coefficients were evaluated. Considering mometasone furoate as an example, suspended drug particle sizes in the range of 1-5 μm did not affect the total nasal epithelial uptake. However, the microscale absorption of suspended drug particles with low solubilities was affected by particle size and this controlled the extent to which the drug penetrated into the distal nasal regions. The nasal-DAC model was demonstrated to be a useful tool in determining the nasal exposure of spray formulations with different drug particle sizes and solubilities. Furthermore, the model illustrated a new strategy for topical nasal drug delivery in which drug particle size is selected to increase the region of epithelial surface exposure using mucociliary clearance while minimizing the drug dose exiting the nasopharynx.

  9. Intradermal Inactivated Poliovirus Vaccine: A Preclinical Dose-Finding Study

    PubMed Central

    Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin

    2015-01-01

    Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial vaccine doses induced antibodies at titers comparable to those after immunization with full human dose delivered intramuscularly. The results suggest that intradermal delivery of IPV may lead to dose-sparing effect and reduction of the vaccination cost. PMID:25391313

  10. Seasonal influenza vaccination during pregnancy and the risks of preterm delivery and small for gestational age birth.

    PubMed

    Ahrens, Katherine A; Louik, Carol; Kerr, Stephen; Mitchell, Allen A; Werler, Martha M

    2014-11-01

    Influenza vaccination is routinely recommended for pregnant women, yet information on perinatal outcomes is sparse. We investigated the associations between trivalent (seasonal) influenza vaccination during pregnancy and the risks of preterm delivery (PTD, live birth <37 weeks gestation) and small for gestational age birth (SGA, <10th percentile in weight for sex-specific gestational age) during the influenza seasons 2006-07 through 2009-10. The study population included 1619 mothers of live-born, non-malformed singleton infants interviewed as part of the Slone Epidemiology Center's Birth Defects Study. Associations between influenza vaccination and PTD and SGA were assessed using Cox and logistic regression models, respectively, with propensity scores used to adjust for confounding. Women vaccinated against pandemic H1N1 were excluded from the analysis. Influenza vaccination during pregnancy showed a near null association with PTD for influenza seasons 2006-07 through 2008-09 compared with unvaccinated women [adjusted hazard ratios (aHR) ranged from 0.79 [95% confidence interval (CI) 0.28, 2.21] in 2007-08 to 1.08 [95% CI: 0.40, 2.95] in 2008-09]. For 2009-10, the risk of PTD was higher in vaccinated women (aHR, 7.81 [95% CI: 2.66, 23.0]). Influenza vaccination was not associated with appreciable risks for SGA for all seasons with sufficient numbers of exposed SGA. Though limited by study size, these findings add support to previous observations of little or no increased risk of PTD or SGA associated with seasonal influenza vaccination for three of the four influenza seasons in our study. The increased risk of PTD observed for the 2009-10 influenza season warrants further investigation. © 2014 John Wiley & Sons Ltd.

  11. Vaccines, our shared responsibility.

    PubMed

    Pagliusi, Sonia; Jain, Rishabh; Suri, Rajinder Kumar

    2015-05-05

    The Developing Countries Vaccine Manufacturers' Network (DCVMN) held its fifteenth annual meeting from October 27-29, 2014, New Delhi, India. The DCVMN, together with the co-organizing institution Panacea Biotec, welcomed over 240 delegates representing high-profile governmental and nongovernmental global health organizations from 36 countries. Over the three-day meeting, attendees exchanged information about their efforts to achieve their shared goal of preventing death and disability from known and emerging infectious diseases. Special praise was extended to all stakeholders involved in the success of polio eradication in South East Asia and highlighted challenges in vaccine supply for measles-rubella immunization over the coming decades. Innovative vaccines and vaccine delivery technologies indicated creative solutions for achieving global immunization goals. Discussions were focused on three major themes including regulatory challenges for developing countries that may be overcome with better communication; global collaborations and partnerships for leveraging investments and enable uninterrupted supply of affordable and suitable vaccines; and leading innovation in vaccines difficult to develop, such as dengue, Chikungunya, typhoid-conjugated and EV71, and needle-free technologies that may speed up vaccine delivery. Moving further into the Decade of Vaccines, participants renewed their commitment to shared responsibility toward a world free of vaccine-preventable diseases. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Recent advances in protein and Peptide drug delivery: a special emphasis on polymeric nanoparticles.

    PubMed

    Patel, Ashaben; Patel, Mitesh; Yang, Xiaoyan; Mitra, Ashim K

    2014-01-01

    Proteins and peptides are widely indicated in many diseased states. Parenteral route is the most commonly em- ployed method of administration for therapeutic proteins and peptides. However, requirement of frequent injections due to short in vivo half-life results in poor patient compliance. Non-invasive drug delivery routes such as nasal, transdermal, pulmonary, and oral offer several advantages over parenteral administration. Intrinsic physicochemical properties and low permeability across biological membrane limit protein delivery via non-invasive routes. One of the strategies to improve protein and peptide absorption is by delivering through nanostructured delivery carriers. Among nanocarriers, polymeric nanoparticles (NPs) have demonstrated significant advantages over other delivery systems. This article summarizes the application of polymeric NPs for protein and peptide drug delivery following oral, nasal, pulmonary, parenteral, transder mal, and ocular administrations.

  13. Recent Advances in Protein and Peptide Drug Delivery: A Special Emphasis on Polymeric Nanoparticles

    PubMed Central

    Patel, Ashaben; Patel, Mitesh; Yang, Xiaoyan; Mitra, Ashim K.

    2015-01-01

    Proteins and peptides are widely indicated in many diseased states. Parenteral route is the most commonly employed method of administration for therapeutic proteins and peptides. However, requirement of frequent injections due to short in vivo half-life results in poor patient compliance. Non-invasive drug delivery routes such as nasal, transdermal, pulmonary, and oral offer several advantages over parenteral administration. Intrinsic physicochemical properties and low permeability across biological membrane limit protein delivery via non-invasive routes. One of the strategies to improve protein and peptide absorption is by delivering through nanostructured delivery carriers. Among nanocarriers, polymeric nanoparticles (NPs) have demonstrated significant advantages over other delivery systems. This article summarizes the application of polymeric NPs for protein and peptide drug delivery following oral, nasal, pulmonary, parenteral, transdermal, and ocular administrations. PMID:25106908

  14. Global challenges of implementing human papillomavirus vaccines

    PubMed Central

    2011-01-01

    Human Papillomavirus vaccines are widely hailed as a sweeping pharmaceutical innovation for the universal benefit of all women. The implementation of the vaccines, however, is far from universal or equitable. Socio-economically marginalized women in emerging and developing, and many advanced economies alike, suffer a disproportionately large burden of cervical cancer. Despite the marketing of Human Papillomavirus vaccines as the solution to cervical cancer, the market authorization (licensing) of the vaccines has not translated into universal equitable access. Vaccine implementation for vulnerable girls and women faces multiple barriers that include high vaccine costs, inadequate delivery infrastructure, and lack of community engagement to generate awareness about cervical cancer and early screening tools. For Human Papillomavirus vaccines to work as a public health solution, the quality-assured delivery of cheaper vaccines must be integrated with strengthened capacity for community-based health education and screening. PMID:21718495

  15. Re-designing the Mozambique vaccine supply chain to improve access to vaccines

    PubMed Central

    Lee, Bruce Y.; Haidari, Leila A.; Prosser, Wendy; Connor, Diana L.; Bechtel, Ruth; Dipuve, Amelia; Kassim, Hidayat; Khanlawia, Balbina; Brown, Shawn T.

    2017-01-01

    Introduction Populations and routine childhood vaccine regimens have changed substantially since supply chains were designed in the 1980s, and introducing new vaccines during the “Decade of Vaccine” may exacerbate existing bottlenecks, further inhibiting the flow of all vaccines. Methods Working with the Mozambique Ministry of Health, our team implemented a new process that integrated HERMES computational simulation modeling and on-the-ground implementers to evaluate and improve the Mozambique vaccine supply chain using a system-re-design that integrated new supply chain structures, information technology, equipment, personnel, and policies. Results The alternative system design raised vaccine availability (from 66% to 93% in Gaza; from 76% to 84% in Cabo Delgado) and reduced the logistics cost per dose administered (from $0.53 to $0.32 in Gaza; from $0.38 to $0.24 in Cabo Delgado) as compared to the multi-tiered system under the current EPI. The alternative system also produced higher availability at lower costs after new vaccine introductions. Since reviewing scenarios modeling deliveries every two months in the north of Gaza, the provincial directorate has decided to pilot this approach diverging from decades of policies dictating monthly deliveries. Discussion Re-design improved not only supply chain efficacy but also efficiency, important since resources to deliver vaccines are limited. The Mozambique experience and process can serve as a model for other countries during the Decade of Vaccines. For the Decade of Vaccines, getting vaccines at affordable prices to the market is not enough. Vaccines must reach the population to be successful. PMID:27576077

  16. Effect of Vaccine Administration Modality on Immunogenicity and Efficacy

    PubMed Central

    Zhang, Lu; Wang, Wei; Wang, Shixia

    2016-01-01

    Summary The many factors impacting the efficacy of a vaccine can be broadly divided into three categories: (1) features of the vaccine itself, including immunogen design, vaccine type, formulation, adjuvant, and dosing; (2) individual variations among vaccine recipients; and (3) vaccine administration-related parameters. While much literature exists related to vaccines, and recently systems biology has started to dissect the impact of individual subject variation on vaccine efficacy, few studies have focused on the role of vaccine administration-related parameters on vaccine efficacy. Parenteral and mucosal vaccinations are traditional approaches for licensed vaccines; novel vaccine delivery approaches, including needless injection and adjuvant formulations, are being developed to further improve vaccine safety and efficacy. This review provides a brief summary of vaccine administration-related factors, including vaccination approach, delivery route, and method of administration, to gain a better understanding of their potential impact on the safety and immunogenicity of candidate vaccines. PMID:26313239

  17. Micro/nanoparticle adjuvants for antileishmanial vaccines: present and future trends.

    PubMed

    Badiee, Ali; Heravi Shargh, Vahid; Khamesipour, Ali; Jaafari, Mahmoud Reza

    2013-01-21

    Leishmania infection continues to have a major impact on public health inducing significant morbidity and mortality mostly in the poorest populations. Drug resistance, toxicity and side effects associated with expensive chemotherapeutic treatments and difficult reservoir control emphasize the need for a safe and effective vaccine which is not available yet. Although, Leishmanization (LZ) was shown to be effective against cutaneous leishmaniasis, standardization and safety are the main problems of LZ. First generation killed parasites demonstrated limited efficacy in phase 3 trials and moreover well defined molecules have not reached to phase 3 yet. Limited efficacy in vaccines against leishmaniasis is partly due to lack of an appropriate adjuvant. Hence, the use of particulate delivery systems as carriers for antigen and/or immunostimulatory adjuvants for effective delivery to the antigen-presenting cells (APCs) is a valuable strategy to enhance vaccine efficacies. Particle-based delivery systems such as emulsions, liposomes, virosomes, and polymeric microspheres have the potential for successfully delivering antigens, which can then be further improved via incorporation of additional antigenic or immustimulatory adjuvant components in or onto the particle carrier system. In this review, we have attempted to provide a list of particulate vaccine delivery systems involved in the production of candidate leishmaniasis vaccines and introduced some potentially useful vaccine delivery systems for leishmaniasis in future experiments. In conclusion, combination vaccines (adjuvant systems) composed of candidate antigens and more importantly well-developed particulate delivery systems, such as lipid-based particles containing immunostimulatory adjuvants, have a chance to succeed as antileishmanial vaccines. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Immediate effect of benzalkonium chloride in decongestant nasal spray on the human nasal mucosal temperature.

    PubMed

    Lindemann, J; Leiacker, R; Wiesmiller, K; Rettinger, G; Keck, T

    2004-08-01

    Benzalkonium chloride is a preservative commonly used in nasal decongestant sprays. It has been suggested that benzalkonium chloride may be harmful to the nasal mucosa. Decongestion with the vasoconstrictor xylometazoline containing benzalkonium chloride has been shown to cause a significant reduction of the nasal mucosal temperature. The purpose of the present study was to determine the short-term influence of xylometazoline nasal spray with and without benzalkonium chloride on the nasal mucosal temperature. Healthy volunteers (30) were included in the study. Fifteen volunteers received xylometazoline nasal spray (1.0 mg/mL) containing benzalkonium chloride (0.1 mg/mL) and 15 age-matched subjects, received xylometazoline nasal spray without benzalkonium chloride. Using a miniaturized thermocouple the septal mucosal temperature was continuously measured at defined intranasal detection sites before and after application of the nasal spray. The mucosal temperature values did not significantly differ between the group receiving xylometazoline containing benzalkonium chloride and the group receiving xylometazoline spray without benzalkonium chloride before and after decongestion (P > 0.05). In both study groups septal mucosal temperatures significantly decreased after decongestion (P < 0.05) because of a reduction of the nasal mucosal blood flow following vasoconstriction. This study indicates that benzalkonium chloride itself does not seem to influence nasal blood flow and nasal mucosal temperature in topical nasal decongestants.

  19. Design of magnetic polyplexes taken up efficiently by dendritic cell for enhanced DNA vaccine delivery.

    PubMed

    Nawwab Al-Deen, F M; Selomulya, C; Kong, Y Y; Xiang, S D; Ma, C; Coppel, R L; Plebanski, M

    2014-02-01

    Dendritic cells (DC) targeting vaccines require high efficiency for uptake, followed by DC activation and maturation. We used magnetic vectors comprising polyethylenimine (PEI)-coated superparamagnetic iron oxide nanoparticles, with hyaluronic acid (HA) of different molecular weights (<10 and 900 kDa) to reduce cytotoxicity and to facilitate endocytosis of particles into DCs via specific surface receptors. DNA encoding Plasmodium yoelii merozoite surface protein 1-19 and a plasmid encoding yellow fluorescent gene were added to the magnetic complexes with various % charge ratios of HA: PEI. The presence of magnetic fields significantly enhanced DC transfection and maturation. Vectors containing a high-molecular-weight HA with 100% charge ratio of HA: PEI yielded a better transfection efficiency than others. This phenomenon was attributed to their longer molecular chains and higher mucoadhesive properties aiding DNA condensation and stability. Insights gained should improve the design of more effective DNA vaccine delivery systems.

  20. Technical Transformation of Biodefense Vaccines

    PubMed Central

    Lu, Shan; Wang, Shixia

    2013-01-01

    Biodefense vaccines are developed against a diverse group of pathogens. Vaccines were developed for some of these pathogens a long time ago but they are facing new challenges to move beyond the old manufacturing technologies. New vaccines to be developed against other pathogens have to determine whether to follow traditional vaccination strategies or to seek new approaches. Advances in basic immunology and recombinant DNA technology have fundamentally transformed the process of formulating a vaccine concept, optimizing protective antigens, and selecting the most effective vaccine delivery approach for candidate biodefense vaccines. PMID:19837293

  1. Surgical management of nasal obstruction.

    PubMed

    Moche, Jason A; Palmer, Orville

    2012-05-01

    The proper evaluation of the patient with nasal obstruction relies on a comprehensive history and physical examination. Once the site of obstruction is accurately identified, the patient may benefit from a trial of medical management. At times however, the definitive treatment of nasal obstruction relies on surgical management. Recognizing the nasal septum, nasal valve, and turbinates as possible sites of obstruction and addressing them accordingly can dramatically improve a patient's nasal breathing. Conservative resection of septal cartilage, submucous reduction of the inferior turbinate, and structural grafting of the nasal valve when appropriate will provide the optimal improvement in nasal airflow and allow for the most stable results. Copyright © 2012. Published by Elsevier Inc.

  2. Snoring and Nasal Congestion

    MedlinePlus

    ... treat the various causes of nasal congestion include: Topical nasal steroid spray Topical nasal antihistamine spray Oral antibiotic (in case of ... include more than just the decrease in oxygen levels at night during the apnea episodes. They also ...

  3. Oral continuous positive airway pressure (CPAP) following nasal injury in a preterm infant.

    PubMed

    Carlisle, H R; Kamlin, C O F; Owen, L S; Davis, P G; Morley, C J

    2010-03-01

    Non-invasive respiratory support is increasingly popular but is associated with complications including nasal trauma. The present report describes a novel method of oral continuous positive airway pressure (CPAP) delivery in an extremely premature infant with severe nasal septum erosion. The distal end of a cut down endotracheal tube was passed through a small hole made in the teat of a dummy (infant pacifier) and sutured in place. The dummy was secured in the infant's mouth and CPAP was delivered to the pharynx. The device was well tolerated and the infant was successfully managed using this technique for 48 days, avoiding endotracheal intubation and ventilation.

  4. [Vaccine application of recombinant herpesviruses].

    PubMed

    Yokoyama, N; Xuan, X; Mikami, T

    2000-04-01

    Recently, genetic engineering using recombinant DNA techniques has been applied to design new viral vaccines in order to reduce some problems which the present viral vaccines have. Up to now, many viruses have been investigated for development of recombinant attenuated vaccines or live viral vectors for delivery of foreign genes coding immunogenic antigens. In this article, we introduced the new vaccine strategy using genetically engineered herpesviruses.

  5. Topical nasal decongestant oxymetazoline (0.05%) provides relief of nasal symptoms for 12 hours.

    PubMed

    Druce, H M; Ramsey, D L; Karnati, S; Carr, A N

    2018-05-22

    Nasal congestion, often referred to as stuffy nose or blocked nose is one of the most prevalent and bothersome symptoms of an upper respiratory tract infection. Oxymetazoline, a widely used intranasal decongestant, offers fast symptom relief, but little is known about the duration of effect. The results of 2 randomized, double-blind, vehicle-controlled, single-dose, parallel, clinical studies (Study 1, n=67; Study 2, n=61) in which the efficacy of an oxymetazoline (0.05% Oxy) nasal spray in patients with acute coryzal rhinitis was assessed over a 12-hour time-period. Data were collected on both subjective relief of nasal congestion (6-point nasal congestion scale) and objective measures of nasal patency (anterior rhinomanometry) in both studies. A pooled study analysis showed statistically significant changes from baseline in subjective nasal congestion for 0.05% oxymetazoline and vehicle at each hourly time-point from Hour 1 through Hour 12 (marginally significant at Hour 11). An objective measure of nasal flow was statistically significant at each time-point up to 12 hours. Adverse events on either treatment were infrequent. The number of subjects who achieved an improvement in subjective nasal congestion scores of at least 1.0 was significantly higher in the Oxy group vs. vehicle at all hourly time-points on a 6-point nasal congestion scale. This study shows for the first time, that oxymetazoline provides both statistically significant and clinically meaningful relief of nasal congestion and improves nasal airflow for up to 12 hours following a single dose.

  6. The Role of Particle-Mediated DNA Vaccines in Biodefense Preparedness

    DTIC Science & Technology

    2005-06-17

    vaccines in biodefense preparedness Hansi J. Deana,T, Joel Haynesa, Connie Schmaljohnb aPowderJect Vaccines , Inc. 8551 Research Way, Middleton, WI 53562...accepted 25 January 2005 Available online 12 April 2005Abstract Particle-mediated epidermal delivery (PMED) of DNA vaccines is based on the acceleration...recent years, data have accumulated on the utility of PMED for delivery of DNA vaccines against a number of viral pathogens, including filoviruses

  7. Evaluation of nasal IgA secretion in normal subjects by nasal spray and aspiration.

    PubMed

    Fujimoto, Chisa; Kido, Hiroshi; Sawabuchi, Takako; Mizuno, Dai; Hayama, Masaki; Yanagawa, Hiroaki; Takeda, Noriaki

    2009-06-01

    Nasal washing (NW) is a popular method for collecting human nasal lavage fluid. However, for NW the subject must be trained, and the method is unsuitable for field studies on untrained subjects. To overcome this problem, we have developed an easy and painless method, a nasal spray and aspiration (NSA) method. This method is different from NW in that the nasal cavity is misted over with saline, and the nasal lavage fluid is aspirated from the nostrils through a silicon tube. First, nasal lavage fluid was obtained twice by NSA with an interval of a week between lavages to evaluate intraindividual variability, and the IgA and protein levels in the nasal lavage fluid were measured by enzyme-linked immunosorbent assay and bicinchoninic acid assay, respectively. Next, the IgA value determined by NSA was compared with that by NW in another 12 normal subjects 2 days after NSA. In 10 normal subjects, mean volume of saline sprayed into the nose was 0.46+/-0.15 ml (mean+/-S.D.). Mean volume of aspirated nasal lavage fluid containing both sprayed saline and nasal secretion was 0.44+/-0.37 ml. The mean IgA level/mg protein in the nasal lavage fluid determined by NSA was 112+/-18 microg/mg protein at the first and 99+/-20 at the second times of measurement, being highly reproducible. The mean value by NSA was 114+/-19 microg/mg protein, being almost the same as that by NW of 99+/-27. These findings suggest that the IgA level/mg protein in nasal lavage fluid determined by NSA instead of NW might be useful for assessing the variability of nasal IgA secretion.

  8. Perceiving nasal patency through mucosal cooling rather than air temperature or nasal resistance.

    PubMed

    Zhao, Kai; Blacker, Kara; Luo, Yuehao; Bryant, Bruce; Jiang, Jianbo

    2011-01-01

    Adequate perception of nasal airflow (i.e., nasal patency) is an important consideration for patients with nasal sinus diseases. The perception of a lack of nasal patency becomes the primary symptom that drives these patients to seek medical treatment. However, clinical assessment of nasal patency remains a challenge because we lack objective measurements that correlate well with what patients perceive. The current study examined factors that may influence perceived patency, including air temperature, humidity, mucosal cooling, nasal resistance, and trigeminal sensitivity. Forty-four healthy subjects rated nasal patency while sampling air from three facial exposure boxes that were ventilated with untreated room air, cold air, and dry air, respectively. In all conditions, air temperature and relative humidity inside each box were recorded with sensors connected to a computer. Nasal resistance and minimum airway cross-sectional area (MCA) were measured using rhinomanometry and acoustic rhinometry, respectively. General trigeminal sensitivity was assessed through lateralization thresholds to butanol. No significant correlation was found between perceived patency and nasal resistance or MCA. In contrast, air temperature, humidity, and butanol threshold combined significantly contributed to the ratings of patency, with mucosal cooling (heat loss) being the most heavily weighted predictor. Air humidity significantly influences perceived patency, suggesting that mucosal cooling rather than air temperature alone provides the trigeminal sensation that results in perception of patency. The dynamic cooling between the airstream and the mucosal wall may be quantified experimentally or computationally and could potentially lead to a new clinical evaluation tool.

  9. Field evaluation of the protective efficacy of Mycobacterium bovis BCG vaccine against bovine tuberculosis.

    PubMed

    Lopez-Valencia, G; Renteria-Evangelista, T; Williams, J de Jesús; Licea-Navarro, A; Mora-Valle, A De la; Medina-Basulto, G

    2010-02-01

    The protective efficacy of Mycobacterium bovis BCG (1 x 10(6) single dose) was evaluated under field conditions. A total of 140 male Holstein Friesian calves, one to two week-old were selected. Two groups of 70 each were formed, one group was vaccinated and the other was injected with a placebo during their second week of age and followed until 12 months of age. The study considered a positive case of tuberculosis to be an animal that had a positive reaction to the three following tests in a row: tuberculin, IFNgamma PPD-B and IFNgamma ESAT6-CFP10 during the 12 months of exposure. The results showed a 59.4% efficacy (IC95%: 47.64-71.16). The non-vaccinated calves were 2.4 times more at risk of becoming infected (IC95%: 1.07-5.68) compared to vaccinated animals. As a complementary test a PCR test was performed using nasal exudates in some animals from both groups using a Mycobacterium complex detection kit. All the positive PCR reactions (5/44) were found in the non-vaccinated animals. These findings suggest that the use of the BCG vaccine, even though it is not capable of protecting 100%, does prevent TB vaccinated animals from excreting bacilli in their nasal secretions at their first year of age. Copyright 2009 Elsevier Ltd. All rights reserved.

  10. Functional anatomy of the nasal bones and adjacent structures. Consequences for nasal surgery.

    PubMed

    Popko, M; Verlinde-Schellekens, S A M W; Huizing, E H; Bleys, R L A W

    2018-03-01

    The periosteum of the nasal bones, the periosteal-perichondrial nasal envelope, and the cartilaginous support of the bony vault were studied in serial coronal sections of four human cadaver noses. To differentiate between the various tissue components, the sections were stained according to Mallory-Cason and Verhoeff-Van Gieson stain. The results demonstrated: 1. the presence of clearly distinguishable layers of the periosteum covering the nasal bones; 2. the presence of a continuous periosteal-perichondrial covering of the bony and cartilaginous nasal vaults; 3. the way the cartilaginous support of the bony vault is constructed. The findings described in the present study may have clinical relevance in nasal surgery.

  11. Intranasal delivery of ciprofloxacin to rats: A topical approach using a thermoreversible in situ gel.

    PubMed

    Sousa, Joana; Alves, Gilberto; Oliveira, Paula; Fortuna, Ana; Falcão, Amílcar

    2017-01-15

    Intranasal administration of antibiotics is an alternative and attractive delivery approach in the treatment of local infections such as chronic rhinosinusitis. This topical route has the advantage of delivering high drug concentrations directly to the site of infection when trying to eradicate the highly resistant bacterial biofilms. The purpose of this study was to assess and compare the pharmacokinetic parameters of ciprofloxacin following intranasal and intravenous administrations to rats in plasma, olfactory bulb and nasal mucosa of two different nasal regions. For intranasal administration a thermoreversible in situ gel was used to increase drug residence time in nasal cavity. Ciprofloxacin concentration time-profile in nasal mucosa of the studied anterior region (at naso- and maxilloturbinates level) was markedly higher after intranasal administration (0.24mg/kg) than that following intravenous administration (10mg/kg), while in nasal mucosa of the more posterior region (at ethmoidal turbinates level) ciprofloxacin concentrations were found to be higher after intranasal administration when the different dose administered by both routes is taken into account. A plateau in ciprofloxacin concentration was observed in nasal mucosa of both studied regions after intranasal administration, suggesting a slow delivery of the drug over a period of time using the nasal gel formulation. In plasma and olfactory bulb, concentration of ciprofloxacin was residual after intranasal administration, which demonstrates this is a safe administration route by preventing systemic and particularly central nervous system adverse effects. Dose-normalized pharmacokinetic parameters of ciprofloxacin exposure to nasal mucosa revealed higher values after intranasal delivery not only in the anterior region but also in the posterior nasal region. In conclusion, topical intranasal administration appears to be advantageous for delivering ciprofloxacin to the biophase, with negligible systemic

  12. Comparison between Perceptual Assessments of Nasality and Nasalance Scores

    ERIC Educational Resources Information Center

    Brunnegard, Karin; Lohmander, Anette; van Doorn, Jan

    2012-01-01

    Background: There are different reports of the usefulness of the Nasometer[TM] as a complement to listening, often as correlation calculations between listening and nasalance measurements. Differences between findings have been attributed to listener experience and types of speech stimuli. Aims: To compare nasalance scores from the Nasometer with…

  13. Novel application for electrochemotherapy: Immersion of nasal cavity in dog.

    PubMed

    Suzuki, Daniela O H; Berkenbrock, José A; de Oliveira, Krishna D; Freytag, Jennifer O; Rangel, Marcelo M M

    2017-08-01

    Electrochemotherapy is a new modality of local cancer treatment that increases the delivery of chemotherapy drugs into tumor cells by applying intense electric fields. This novel electrochemotherapy application was applied as an adjuvant to surgery and eliminated intranasal tumors in dog. The treatment challenges are the surgery limitations due to anatomy and residual tumor in the bone cavity. Most of the tumoral mass on nasal cavity was surgically removed. The internal nasal cavity was immersed in liquid and bleomycin before applying electric field. The solution was necessary to increase the superficial contact between plate electrodes and residual tumor. The numerical study demonstrated electrochemotherapy efficiency in different clinical situations. The proximity between electrodes and bone (<3 mm) and bone irregularities affect the electric field distribution on tumoral tissue. The tumoral tissue around bone protuberances tends to be eliminated. Electrochemotherapy with plate electrodes inside the cavity might not be effective. Different values of electric conductivity solution were studied; the ideal value was 0.5 S/m. The numerical and experimental results confirm the successful application of electrochemotherapy on dog nasal cavity. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  14. Global Vaccine and Immunization Research Forum: Opportunities and challenges in vaccine discovery, development, and delivery.

    PubMed

    Ford, Andrew Q; Touchette, Nancy; Hall, B Fenton; Hwang, Angela; Hombach, Joachim

    2016-03-18

    The World Health Organization, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and the Bill & Melinda Gates Foundation convened the first Global Vaccine and Immunization Research Forum (GVIRF) in March 2014. This first GVIRF aimed to track recent progress of the Global Vaccine Action Plan research and development agenda, identify opportunities and challenges, promote partnerships in vaccine research, and facilitate the inclusion of all stakeholders in vaccine research and development. Leading scientists, vaccine developers, and public health officials from around the world discussed scientific and technical challenges in vaccine development, research to improve the impact of immunization, and regulatory issues. This report summarizes the discussions and conclusions from the forum participants. Copyright © 2016. Published by Elsevier Ltd.. All rights reserved.

  15. Nasal vaccination with troponin reduces troponin specific T-cell responses and improves heart function in myocardial ischemia–reperfusion injury

    PubMed Central

    Frenkel, Dan; Pachori, Alok S.; Zhang, Lunan; Dembinsky-Vaknin, Adi; Farfara, Dorit; Petrovic-Stojkovic, Sanja; Dzau, Victor J.

    2009-01-01

    Myocardial ischemia with subsequent reperfusion (MI/R) can lead to significant myocardial damage. Ischemia initiates inflammation at the blood–microvascular endothelial cell interface and contributes significantly to both acute injury and repair of the damaged tissue. We have found that MI/R injury in mice is associated with a cellular immune response to troponin. Myocardial cells exclusively synthesize troponin and release the troponin into the bloodstream following injury. Mucosally administered proteins induce T cells that secrete anti-inflammatory cytokines such as IL-10 and transforming growth factor β at the anatomical site where the protein localizes. We found that nasal administration of the three subunits of troponin (C, I and T isoforms), given prior to or 1 h following MI/R, decreased infarct size by 40% measured 24 h later. At 1.5 months following MI/R, there was a 50% reduction in infarct size and improvement in cardiac function as measured by echocardiography. Protection was associated with a reduction of cellular immunity to troponin. Immunohistochemistry demonstrated increased IL-10 and reduced IFN-γ in the area surrounding the ischemic infarct following nasal troponin. Adoptive transfer of CD4+ T cells to mice from nasally troponin-treated mice 1 h after the MI/R decreased infarct size by 72%, whereas CD4+ T cells from IL-10−/− mice or nasally BSA-treated mice had no effect. Our results demonstrate that IL-10-secreting CD4+ T cells induced by nasal troponin reduce injury following MI/R. Modulation of cardiac inflammation by nasal troponin provides a novel treatment to decrease myocardial damage and enhance recovery after myocardial ischemia. PMID:19515797

  16. Topical Drug Delivery in Chronic Rhinosinusitis Patients before and after Sinus Surgery Using Pulsating Aerosols

    PubMed Central

    Möller, Winfried; Schuschnig, Uwe; Celik, Gülnaz; Münzing, Wolfgang; Bartenstein, Peter; Häussinger, Karl; Kreyling, Wolfgang G.; Knoch, Martin

    2013-01-01

    Objectives Chronic rhinosinusitis (CRS) is a common chronic disease of the upper airways and has considerable impact on quality of life. Topical delivery of drugs to the paranasal sinuses is challenging, therefore the rate of surgery is high. This study investigates the delivery efficiency of a pulsating aerosol in comparison to a nasal pump spray to the sinuses and the nose in healthy volunteers and in CRS patients before and after sinus surgery. Methods 99mTc-DTPA pulsating aerosols were applied in eleven CRSsNP patients without nasal polyps before and after sinus surgery. In addition, pulsating aerosols were studied in comparison to nasal pump sprays in eleven healthy volunteers. Total nasal and frontal, maxillary and sphenoidal sinus aerosol deposition and lung penetration were assessed by anterior and lateral planar gamma camera imaging. Results In healthy volunteers nasal pump sprays resulted in 100% nasal, non-significant sinus and lung deposition, while pulsating aerosols resulted 61.3+/-8.6% nasal deposition and 38.7% exit the other nostril. 9.7+/-2.0 % of the nasal dose penetrated into maxillary and sphenoidal sinuses. In CRS patients, total nasal deposition was 56.7+/-13.3% and 46.7+/-12.7% before and after sinus surgery, respectively (p<0.01). Accordingly, maxillary and sphenoidal sinus deposition was 4.8+/-2.2% and 8.2+/-3.8% of the nasal dose (p<0.01). Neither in healthy volunteers nor in CRS patients there was significant dose in the frontal sinuses. Conclusion In contrast to nasal pump sprays, pulsating aerosols can deliver significant doses into posterior nasal spaces and paranasal sinuses, providing alternative therapy options before and after sinus surgery. Patients with chronic lung diseases based on clearance dysfunction may also benefit from pulsating aerosols, since these diseases also manifest in the upper airways. PMID:24040372

  17. Perceiving Nasal Patency through Mucosal Cooling Rather than Air Temperature or Nasal Resistance

    PubMed Central

    Zhao, Kai; Blacker, Kara; Luo, Yuehao; Bryant, Bruce; Jiang, Jianbo

    2011-01-01

    Adequate perception of nasal airflow (i.e., nasal patency) is an important consideration for patients with nasal sinus diseases. The perception of a lack of nasal patency becomes the primary symptom that drives these patients to seek medical treatment. However, clinical assessment of nasal patency remains a challenge because we lack objective measurements that correlate well with what patients perceive.The current study examined factors that may influence perceived patency, including air temperature, humidity, mucosal cooling, nasal resistance, and trigeminal sensitivity. Forty-four healthy subjects rated nasal patency while sampling air from three facial exposure boxes that were ventilated with untreated room air, cold air, and dry air, respectively. In all conditions, air temperature and relative humidity inside each box were recorded with sensors connected to a computer. Nasal resistance and minimum airway cross-sectional area (MCA) were measured using rhinomanometry and acoustic rhinometry, respectively. General trigeminal sensitivity was assessed through lateralization thresholds to butanol. No significant correlation was found between perceived patency and nasal resistance or MCA. In contrast, air temperature, humidity, and butanol threshold combined significantly contributed to the ratings of patency, with mucosal cooling (heat loss) being the most heavily weighted predictor. Air humidity significantly influences perceived patency, suggesting that mucosal cooling rather than air temperature alone provides the trigeminal sensation that results in perception of patency. The dynamic cooling between the airstream and the mucosal wall may be quantified experimentally or computationally and could potentially lead to a new clinical evaluation tool. PMID:22022361

  18. Oral Vaccination with a DNA Vaccine Encoding Capsid Protein of Duck Tembusu Virus Induces Protection Immunity

    PubMed Central

    Shen, Haoyue; Jia, Renyong; Wang, Mingshu; Chen, Shun; Zhu, Dekang; Liu, Mafeng; Zhao, Xinxin; Yang, Qiao; Wu, Ying; Liu, Yunya; Zhang, Ling; Yin, Zhongqiong; Jing, Bo

    2018-01-01

    The emergence of duck tembusu virus (DTMUV), a new member of the Flavivirus genus, has caused great economical loss in the poultry industry in China. Since the outbreak and spread of DTMUV is hard to control in a clinical setting, an efficient and low-cost oral delivery DNA vaccine SL7207 (pVAX1-C) based on the capsid protein of DTMUV was developed and evaluated in this study. The antigen capsid protein was expressed from the DNA vaccine SL7207 (pVAX1-C), both in vitro and in vivo. The humoral and cellular immune responses in vivo were observed after oral immunization with the SL7207 (pVAX1-C) DNA vaccine. High titers of the specific antibody against the capsid protein and the neutralizing antibody against the DTMUV virus were both detected after inoculation. The ducks were efficiently protected from lethal DTMUV exposure by the SL7207 (pVAX1-C) vaccine in this experiment. Taken together, we demonstrated that the capsid protein of DTMUV possesses a strong immunogenicity against the DTMUV infection. Moreover, an oral delivery of the DNA vaccine SL7207 (pVAX1-C) utilizing Salmonella SL7207 was an efficient way to protect the ducks against DTMUV infection and provides an economic and fast vaccine delivery strategy for a large scale clinical use. PMID:29642401

  19. Efficacy of thiolated eudragit microspheres as an oral vaccine delivery system to induce mucosal immunity against enterotoxigenic Escherichia coli in mice.

    PubMed

    Lee, Won-Jung; Cha, Seungbin; Shin, Minkyoung; Jung, Myunghwan; Islam, Mohammad Ariful; Cho, Chong-su; Yoo, Han Sang

    2012-05-01

    A vaccine delivery system based on thiolated eudragit microsphere (TEMS) was studied in vivo for its ability to elicit mucosal immunity against enterotoxigenic Escherichia coli (ETEC). Groups of mice were orally immunized with F4 or F18 fimbriae of ETEC and F4 or F18 loaded in TEMS. Mice that were orally administered with F4 or F18 loaded TEMS showed higher antigen-specific IgG antibody responses in serum and antigen-specific IgA in saliva and feces than mice that were immunized with antigens only. In addition, oral vaccination of F4 or F18 loaded TEMS resulted in higher numbers of IgG and IgA antigen-specific antibody secreting cells in the spleen, lamina propria, and Peyer's patches of immunized mice than other groups. Moreover, TEMS administration loaded with F4 or F18 induced mixed Th1 and Th2 type responses based on similarly increased levels of IgG1 and IgG2a. These results suggest that F4 or F18 loaded TEMS may be a promising candidate for an oral vaccine delivery system to elicit systemic and mucosal immunity against ETEC. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Comparison of Early-period Results of Nasal Splint and Merocel Nasal Packs in Septoplasty

    PubMed Central

    Bingöl, Fatih; Budak, Ali; Şimşek, Eda; Kılıç, Korhan; Bingöl, Buket Özel

    2017-01-01

    Objective Several types of nasal packs are used postoperatively in septoplasty. In this study, we compared two commonly used nasal packing materials, the intranasal septal splint with airway and Merocel tampon, in terms of pain, bleeding, nasal obstruction, eating difficulties, discomfort in sleep, and pain and bleeding during removal of packing in the early period. Methods The study group included 60 patients undergoing septoplasty. Patients were divided into two groups (n=30 in each group). An intranasal splint with airway was used for the patients in the first group after septoplasty, while Merocel nasal packing was used for the second group. Patients were investigated in terms of seven different factors - pain, bleeding while the tampon was in place, nasal obstruction, eating difficulties, night sleep, pain during removal of the nasal packing, and bleeding after removal of packing. Results There was no statistically significant difference between the groups in terms of pain 24 hours after operation (p=0.05), while visual analog scale (VAS) scores for nasal obstruction, night sleep, eating difficulties, and pain during packing removal were lower in the nasal splint group with a statistically significant difference (p<0.05). There was no statistically significant difference between the groups in terms of postoperative bleeding (p=0.23). Significantly less bleeding occurred during removal of the packing in the nasal splint group (p<0.05). Conclusion Our study indicates that the nasal splint was more comfortable and effective in terms of causing lesser bleeding and pain during removal of packing. PMID:29392071

  1. Severe post-vaccination reaction to 17D yellow fever vaccine in Nigeria.

    PubMed

    Oyelami, S A; Olaleye, O D; Oyejide, C O; Omilabu, S A; Fatunla, B A

    1994-01-01

    An unusual outbreak of post-vaccination reactions to 17D yellow fever vaccine occurred at Shaki, Nigeria, in May 1987. Twenty-five of the affected people were treated at the Baptist Hospital Shaki. The patients presented with rapidly progressing swelling of the left arm with associated fever and other constitutional symptoms few hours after inoculation with the vaccine. Some of the patients developed gangrene of the affected limb, five of them went into coma and died. Poor hygiene and improper handling of vaccine as well as contamination of vaccine from the source are possible causes. A review of vaccine delivery strategies especially at local community levels; sound training, supervision of vaccinators and health education are strongly recommended to prevent reoccurrence of similar reactions.

  2. Ebola Vaccination Using a DNA Vaccine Coated on PLGA-PLL/γPGA Nanoparticles Administered Using a Microneedle Patch.

    PubMed

    Yang, Hung-Wei; Ye, Ling; Guo, Xin Dong; Yang, Chinglai; Compans, Richard W; Prausnitz, Mark R

    2017-01-01

    Ebola DNA vaccine is incorporated into PLGA-PLL/γPGA nanoparticles and administered to skin using a microneedle (MN) patch. The nanoparticle delivery system increases vaccine thermostability and immunogenicity compared to free vaccine. Vaccination by MN patch produces stronger immune responses than intramuscular administration. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Nasalance measures in Cantonese-speaking women.

    PubMed

    Whitehill, T L

    2001-03-01

    To establish and evaluate stimulus materials for nasalance measurement in Cantonese speakers, to provide normative data for Cantonese-speaking women, and to evaluate session-to-session reliability of nasalance measures. One hundred forty-one Cantonese-speaking women with normal resonance who were students in the Department of Speech and Hearing Sciences, University of Hong Kong. Participants read aloud four speech stimuli: oral sentences, nasal sentences, an oral paragraph (similar to the Zoo Passage), and an oral-nasal paragraph (similar to the Rainbow Passage). Data were collected and analyzed using the Kay Nasometer 6200. Data collection was repeated for a subgroup of speakers (n = 28) on a separate day. Nasalance materials were evaluated by using statistical tests of difference and correlation. Group mean (standard deviation) nasalance scores for oral sentences, nasal sentences, oral paragraph, and oral-nasal paragraph were 16.79 (5.99), 55.67 (7.38), 13.68 (7.16), and 35.46 (6.22), respectively. There was a significant difference in mean nasalance scores for oral versus nasal materials. Correlations between stimuli were as expected, ranging from 0.43 to 0.91. Session-to-session reliability was within 5 points for over 95% of speakers for the oral stimuli but for less than 76% of speakers for the nasal and oral-nasal stimuli. Standard nasalance materials have been developed for Cantonese, and normative data have been established for Cantonese women. Evaluation of materials indicated acceptable differentiation between oral and nasal materials. Two stimuli (nasal sentences and oral paragraph) are recommended for future use. Comparison with findings from other languages showed similarities in scores; possible language-specific differences are discussed. Session-to-session reliability was poorer for nasal than oral stimuli.

  4. Nasal septal hematoma

    MedlinePlus

    ... medlineplus.gov/ency/article/001292.htm Nasal septal hematoma To use the sharing features on this page, please enable JavaScript. A nasal septal hematoma is a collection of blood within the septum ...

  5. Immune response in domestic ducks following intradermal delivery of inactivated vaccine against H5N1 highly pathogenic avian influenza virus adjuvanted with oligodeoxynucleotides containing CpG motifs.

    PubMed

    Yuk, Seong-Su; Lee, Dong-Hun; Park, Jae-Keun; To, Eredene-Ochir; Kwon, Jung-Hoon; Noh, Jin-Yong; Gomis, Susantha; Song, Chang-Seon

    2015-08-01

    Ducks are a natural reservoir for H5N1 highly pathogenic avian influenza (HPAI) viruses, which produces a range of clinical outcomes from asymptomatic infections to severe disease with mortality. Vaccination against HPAI is one of the few methods available for controlling avian influenza virus (AIV) infection in domestic ducks; therefore, it is necessary to improve vaccine efficacy against HPAI in domestic ducks. However, few studies have focused on enhancing the immune response by testing alternative administration routes and adjuvants. While attempting to maximize the efficacy of a vaccine, it is important to select an appropriate vaccine delivery route and adjuvant to elicit an enhanced immune response. Although several studies have indicated that the vaccination of ducks against HPAI viruses has offered protection against lethal virus challenge, the immunogenicity of the vaccine still requires improvement. In this study, we characterized the immune response following a novel vaccination strategy against H5N1 HPAI virus in domestic ducks. Our novel intradermal delivery system and the application of the cytosine-phosphodiester-guanine (CpG) oligodeoxynucleotide (ODN) adjuvant allowed us to obtain information regarding the sustained vaccine immunity. Compared with the intramuscular route of vaccination, the intradermal route resulted in higher antibody titer as well as lower antibody deviation following secondary vaccination. In addition, the use of a CpG-ODN adjuvant had a dose-sparing effect on antibody titer. Furthermore, when a high dose of antigen was used, the CpG-ODN-adjuvanted vaccine maintained a high mean antibody titer. This data demonstrates that intradermal immunization combined with administration of CpG-ODN as an adjuvant may be a promising strategy for improving vaccine efficacy in domestic ducks. © 2015 Poultry Science Association Inc.

  6. Same Noses, Different Nasalance Scores: Data from Normal Subjects and Cleft Palate Speakers for Three Systems for Nasalance Analysis

    ERIC Educational Resources Information Center

    Bressmann, Tim; Klaiman, Paula; Fischbach, Simone

    2006-01-01

    Nasalance scores from the Nasometer, the NasalView and the OroNasal System were compared. The data was collected from 50 normal participants and 19 hypernasal patients with cleft palate. The Nasometer had the lowest nasalance scores for the non-nasal Zoo Passage and that the OroNasal System had the lowest nasalance scores for the Nasal Sentences.…

  7. Nasal hydropulsion.

    PubMed

    Elizabeth, Ashbaugh

    2013-08-01

    Intranasal tumors of dogs and cats pose a diagnostic and therapeutic challenge for the small animal practitioner. A simplified flushing technique to biopsy and debulk nasal tumors, that often results in immediate clinical relief for the patient is described. This technique can also be utilized to remove nasal foreign bodies. © 2013 Elsevier Inc. All rights reserved.

  8. Economics of animal vaccination.

    PubMed

    McLeod, A; Rushton, J

    2007-08-01

    This paper describes the steps that might be used in assessing the economic justification for using vaccination to control animal disease, and the way that vaccination is financed and administered. It describes decisions that have been taken with respect to preserving international trade, and issues related to protection of livelihoods. Regardless of the motivation for vaccination, its costs can usually be shared between the public and private sectors. Cost-effective vaccination requires methods of delivery to be adapted to livestock production systems. The paper concludes by suggesting questions around the use of vaccination that would merit further economic analysis.

  9. Ipratropium Nasal Spray

    MedlinePlus

    ... follow these steps: Remove the clear plastic dust cap and the safety clip from the nasal spray ... the other nostril. Replace the clear plastic dust cap and safety clip. If the nasal tip becomes ...

  10. Nasal fracture - aftercare

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000554.htm Nasal fracture - aftercare To use the sharing features on this ... that gives your nose its shape. A nasal fracture occurs when the bony part of your nose ...

  11. Nasal Wash Treatment

    MedlinePlus

    ... Guidelines Wash your hands. Make the nasal wash solution. Do not use tap water for the nasal ... Whichever water you use to make the saline solution, replace container or water at least weekly. To ...

  12. Beclomethasone Nasal Spray

    MedlinePlus

    ... the lining of the nose) after nasal polyp removal surgery. Beclomethasone nasal spray should not be used ... room temperature and away from excess heat and moisture (not in the bathroom).Unneeded medications should be ...

  13. Nasal Harmony in Aguaruna.

    ERIC Educational Resources Information Center

    Moon, Gui-Sun

    A discussion of the nasal harmony of Aguaruna, a language of the Jivaroan family in South America, approaches the subject from the viewpoint of generative phonology. This theory of phonology proposes an underlying nasal consonant, later deleted, that accounts for vowel nasalization. Complex rules that suppose a complex system of vowel and…

  14. Intranasal delivery of antiviral siRNA.

    PubMed

    Barik, Sailen

    2011-01-01

    Intranasal administration of synthetic siRNA is an effective modality of RNAi delivery for the prevention and therapy of respiratory diseases, including pulmonary infections. Vehicles used for nasal siRNA delivery include established as well as novel reagents, many of which have been recently optimized. In general, they all promote significant uptake of siRNA into the lower respiratory tract, including the lung. When properly designed and optimized, these siRNAs offer significant protection against respiratory viruses such as influenza virus, parainfluenza virus and respiratory syncytial virus (RSV). Nasally administered siRNA remains within the lung and does not access systemic blood flow, as judged by its absence in other major organs such as liver, heart, kidney, and skeletal muscle. Adverse immune reaction is generally not encountered, especially when immunogenic and/or off-target siRNA sequences and toxic vehicles are avoided. In fact, siRNA against RSV has entered Phase II clinical trials in human with promising results. Here, we provide a standardized procedure for using the nose as a specific route for siRNA delivery into the lung of laboratory animals. It should be clear that this simple and efficient system has enormous potential for therapeutics.

  15. Modified thermoresponsive Poloxamer 407 and chitosan sol-gels as potential sustained-release vaccine delivery systems.

    PubMed

    Kojarunchitt, Thunjiradasiree; Baldursdottir, Stefania; Dong, Yao-Da; Boyd, Ben J; Rades, Thomas; Hook, Sarah

    2015-01-01

    Thermoresponsive, particle-loaded, Poloxamer 407 (P407)-Pluronic-R® (25R4) or chitosan-methyl cellulose (MC) formulations were developed as single-dose, sustained release vaccines. The sol-gels, loaded either with a particulate vaccine (cubosomes) or soluble antigen (ovalbumin) and adjuvants (Quil A and monophosphoryl lipid A), were free-flowing liquids at room temperature and formed stable gels at physiological temperatures. Rheological results showed that both systems meet the criteria of being thermoresponsive gels. The P407-25R4 sol-gels did not significantly sustain the release of antigen in vivo while the chitosan-MC sol-gels sustained the release of antigen up to at least 14 days after administration. The chitosan-MC sol-gels stimulated both cellular and humoral responses. The inclusion of cubosomes in the sol-gels did not provide a definitive beneficial effect. Further analysis of the formulations with small-angle X-ray scattering (SAXS) revealed that while cubosomes were stable in chitosan-MC gels they were not stable in P407-25R4 formulations. The reason for the mixed response to cubosome-loaded vehicles requires more investigation, however it appears that the cubosomes did not facilitate synchronous vaccine release and may in fact retard release, reducing efficacy in some cases. From these results, chitosan-MC sol-gels show potential as sustained release vaccine delivery systems, as compared to the P407-25R4 system that had a limited ability to sustain antigen release. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. External Nasal Neuralgia: A Neuropathic Pain Within the Territory of the External Nasal Nerve.

    PubMed

    García-Moreno, Héctor; Aledo-Serrano, Ángel; Gimeno-Hernández, Jesús; Cuadrado, María-Luz

    2015-10-01

    Nasal pain is a challenging diagnosis and very little has been reported in the neurological literature. The nose is a sophisticated structure regarding its innervation, which is supplied by the first and second divisions of the trigeminal nerve. Painful cranial neuropathies are an important group in the differential diagnosis, although they have been described only scarcely. Here, we report a case that can conform a non-traumatic external nasal nerve neuralgia. A 76-year-old woman was referred to our office due to pain in her left nose. She was suffering from daily excruciating attacks, which were strictly limited to the territory supplied by her left external nasal nerve (left ala nasi and apex nasi). She denied previous traumatisms and the ancillary tests did not yield any underlying pathology. An anesthetic blockade of her left external nasal nerve achieved a marked reduction of the number of episodes as well as their intensity. External nasal neuralgia seems a specific neuralgia causing nasal pain. Anesthetic blockades of the external nasal nerve may be a valid treatment for this condition. © 2015 American Headache Society.

  17. Modified Vaccinia Ankara Virus Vaccination Provides Long-Term Protection against Nasal Rabbitpox Virus Challenge.

    PubMed

    Jones, Dorothy I; McGee, Charles E; Sample, Christopher J; Sempowski, Gregory D; Pickup, David J; Staats, Herman F

    2016-07-01

    Modified vaccinia Ankara virus (MVA) is a smallpox vaccine candidate. This study was performed to determine if MVA vaccination provides long-term protection against rabbitpox virus (RPXV) challenge, an animal model of smallpox. Two doses of MVA provided 100% protection against a lethal intranasal RPXV challenge administered 9 months after vaccination. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  18. Does rhinoplasty improve nasal breathing?

    PubMed

    Xavier, Rui

    2010-08-01

    Rhinoplasty is a surgical procedure that aims to improve nasal aesthetics and nasal breathing. The aesthetic improvement of the nose is usually judged subjectively by the patient and the surgeon, but the degree of improvement of nasal obstruction is difficult to assess by clinical examination only. The measurement of peak nasal inspiratory flow (PNIF) is a reliable tool that has been shown to correlate with other objective methods of assessing nasal breathing and with patients' symptoms of nasal obstruction. Twenty-three consecutive patients undergoing rhinoplasty have been evaluated by measurement of PNIF before and after surgery. All but three patients had an increase in PNIF after surgery. The mean preoperative PNIF was 86.5 L/min and the mean postoperative PNIF was 123.0 L/min ( P < 0.001). Not surprisingly, the greatest improvement in PNIF was achieved when bilateral spreader grafts were used. This study suggests that rhinoplasty does improve nasal breathing. (c) Thieme Medical Publishers

  19. Development of in vitro models to demonstrate the ability of PecSys®, an in situ nasal gelling technology, to reduce nasal run-off and drip

    PubMed Central

    2013-01-01

    Many of the increasing number of intranasal products available for either local or systemic action can be considered sub-optimal, most notably where nasal drip or run-off give rise to discomfort/tolerability issues or reduced/variable efficacy. PecSys, an in situ gelling technology, contains low methoxy (LM) pectin which gels due to interaction with calcium ions present in nasal fluid. PecSys is designed to spray readily, only forming a gel on contact with the mucosal surface. The present study employed two in vitro models to confirm that gelling translates into a reduced potential for drip/run-off: (i) Using an inclined TLC plate treated with a simulated nasal electrolyte solution (SNES), mean drip length [±SD, n = 10] was consistently much shorter for PecSys (1.5 ± 0.4 cm) than non-gelling control (5.8 ± 1.6 cm); (ii) When PecSys was sprayed into a human nasal cavity cast model coated with a substrate containing a physiologically relevant concentration of calcium, PecSys solution was retained at the site of initial deposition with minimal redistribution, and no evidence of run-off/drip anteriorly or down the throat. In contrast, non-gelling control was significantly more mobile and consistently redistributed with run-off towards the throat. Conclusion In both models PecSys significantly reduced the potential for run-off/drip ensuring that more solution remained at the deposition site. In vivo, this enhancement of retention will provide optimum patient acceptability, modulate drug absorption and maximize the ability of drugs to be absorbed across the nasal mucosa and thus reduce variability in drug delivery. PMID:22803832

  20. Strategies to implement maternal vaccination: A comparison between standing orders for midwife delivery, a hospital based maternal immunisation service and primary care.

    PubMed

    Krishnaswamy, Sushena; Wallace, Euan M; Buttery, Jim; Giles, Michelle L

    2018-03-20

    Maternal vaccination is a safe and effective strategy to reduce maternal and neonatal morbidity and mortality from pertussis and influenza. However, despite recommendations for maternal vaccination since 2010, uptake remains suboptimal. Barriers to uptake have been studied widely and include lack of integration of vaccination into routine pregnancy care and access to vaccination services. Standing orders for administration of vaccines without the need for a physician review or prescription have been demonstrated to improve uptake as part of multi-model interventions to increase antenatal influenza and post-partum pertussis vaccination. Monash Health is a university-affiliated, public healthcare network in Melbourne, Australia providing maternity services across three hospitals. In this study we compared three different immunisation models - an immunisation nurse-led immunisation service, standing orders for midwife-administered pertussis vaccination within pregnancy care clinics, and delivery by general practitioners in primary care. Uptake of maternal pertussis vaccine was measured as recorded in the state-wide perinatal data collection tool. Uptake improved significantly at all three hospitals over the study period with the most significant change (39% to 91%, p < .001) noted at the hospital where standing orders were introduced. Our study highlights the diversity of immunisation service models available in maternity care settings. We demonstrated significant improvement in uptake of maternal pertussis vaccination with introduction of midwife-administered vaccination but each maternity service should consider the model best suited to their needs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Intranasal delivery: physicochemical and therapeutic aspects.

    PubMed

    Costantino, Henry R; Illum, Lisbeth; Brandt, Gordon; Johnson, Paul H; Quay, Steven C

    2007-06-07

    Interest in intranasal (IN) administration as a non-invasive route for drug delivery continues to grow rapidly. The nasal mucosa offers numerous benefits as a target issue for drug delivery, such as a large surface area for delivery, rapid drug onset, potential for central nervous system delivery, and no first-pass metabolism. A wide variety of therapeutic compounds can be delivered IN, including relatively large molecules such as peptides and proteins, particularly in the presence of permeation enhancers. The current review provides an in-depth discussion of therapeutic aspects of IN delivery including consideration of the intended indication, regimen, and patient population, as well as physicochemical properties of the drug itself. Case examples are provided to illustrate the utility of IN dosing. It is anticipated that the present review will prove useful for formulation scientists considering IN delivery as a delivery route.

  2. Cholesteryl Pullulan Encapsulated TNF-α Nanoparticles Are an Effective Mucosal Vaccine Adjuvant against Influenza Virus

    PubMed Central

    Nagatomo, Daiki; Taniai, Madoka; Ariyasu, Harumi; Taniguchi, Mutsuko; Aga, Miho; Ariyasu, Toshio; Ohta, Tsunetaka; Fukuda, Shigeharu

    2015-01-01

    We encapsulated tumor necrosis factor-α (TNF-α), a major proinflammatory cytokine, into cholesteryl pullulan (CHP) to prepare TNF/CHP nanoparticles. In this report, we describe the immune-enhancing capability of the nanoparticles to act as a vaccine adjuvant. TNF/CHP nanoparticles showed excellent storage stability and enhanced host immune responses to external immunogens. The nanoparticles were effective via the nasal route of administration for inducing systemic IgG1 as well as mucosal IgA. We applied the nanoparticles in a model experimental influenza virus infection to investigate their adjuvant ability. TNF/CHP nanoparticles combined with a conventional split vaccine protected mice via nasal administration against a lethal challenge of A/PR/8/34 (H1N1) influenza virus. Mechanistic studies showed that the nanoparticles enhanced antigen uptake by dendritic cells (DCs) and moderately induced the expression of inflammation-related genes in nasopharynx lymphoid tissue (NALT), leading to the activation of both B and T cells. Preliminary safety study revealed no severe toxicity to TNF/CHP nanoparticles. Slight-to-moderate influences in nasal mucosa were observed only in the repeated administration and they seemed to be reversible. Our data show that TNF/CHP nanoparticles effectively enhance both humoral and cellular immunity and could be a potential adjuvant for vaccines against infectious diseases, especially in the mucosa. PMID:26421290

  3. Management of nasal septal perforation using silicone nasal septal button

    PubMed Central

    Mullace, M; Gorini, E; Sbrocca, M; Artesi, L; Mevio, N

    2006-01-01

    Summary Nasal septal perforation may present with various symptoms: epistaxis, crusting, secondary infection, whistling and nasal obstruction. Perforation may be treated by conservative pharmacological treatment or closed by surgical approach. A useful alternative is mechanical obturation, achieved inserting a prosthesis. The present report refers to a study on 15 patients (10 male, 5 female, mean age 38.5 years) treated by insertion of a one-piece or two-piece silicone septal button (Xomed). In the follow-up period, insertion of the nasal button reduced epistaxis, eliminated whistling during inspiration, and reduced nasal obstruction and crusting around the margin of the perforation. Contraindications are presence of acute infection with osteitis, chronic septal disease (Wegener), neoplasia and extremely large perforations. The latest buttons appear to be superior to the conventional type on account of plasticity and adaptability which offer greater conformity to the septum. This study also reveals that the new septal button is well tolerated by patients. PMID:18236638

  4. Complications of Nasal Bone Fractures.

    PubMed

    Hwang, Kun; Yeom, Seung Han; Hwang, Suk Hyun

    2017-05-01

    The aim of this study was to perform a systematic review of the treatment of nasal bone fractures. The search terms ("nasal bone fracture" AND complication) and ("nasal bone fracture" AND [anosmia OR olfaction OR olfactory nerve OR smell]) and (anosmia AND ["nasal preparation" OR "nasal antiseptics"]) were used to search PubMed and SCOPUS. Of the 500 titles, 40 full papers were reviewed. One paper was excluded, and 3 mined papers were added. Ultimately, 12 papers were analyzed. The overall deformity rate was 10.4% ± 4.8%. No significant differences were found between patients who underwent closed reduction (14.7% ± 7.3%) and those who underwent open reduction (9.4% ± 4.4%), between those who underwent local anesthesia (5.8% ± 4.5%), and those who underwent general anesthesia (8.8% ± 3.8%), or between those who received timely treatment (5.7%) and those whose treatment was delayed (9.0%). Septal deviation occurred in 10.0% of patients as a sequela of nasal bone fracture. The nasal obstruction rate was 10.5% ± 5.3%. Fewer patients of nasal obstruction occurred in the open reduction patients (6.9% ± 4.4%) than in the closed reduction patients (15.2%). One patient of epiphora and 1 patient of diplopia were reportedAmong the 77 patients with nasal bone fractures, 29 (37.7% ± 11.3%) complained of olfactory disturbances. No significant associations were found between the type of fracture and the presence of olfactory disturbances. It is recommended for providers to explain to patients that approximately one-tenth of nasal bone fractures exhibit deformity, septal deviation, or nasal obstruction after surgery. Surgeons should take considerable care to avoid the olfactory mucosa during reduction surgery.

  5. Changes in nasal airflow and heat transfer correlate with symptom improvement after surgery for nasal obstruction.

    PubMed

    Kimbell, J S; Frank, D O; Laud, Purushottam; Garcia, G J M; Rhee, J S

    2013-10-18

    Surgeries to correct nasal airway obstruction (NAO) often have less than desirable outcomes, partly due to the absence of an objective tool to select the most appropriate surgical approach for each patient. Computational fluid dynamics (CFD) models can be used to investigate nasal airflow, but variables need to be identified that can detect surgical changes and correlate with patient symptoms. CFD models were constructed from pre- and post-surgery computed tomography scans for 10 NAO patients showing no evidence of nasal cycling. Steady-state inspiratory airflow, nasal resistance, wall shear stress, and heat flux were computed for the main nasal cavity from nostrils to posterior nasal septum both bilaterally and unilaterally. Paired t-tests indicated that all CFD variables were significantly changed by surgery when calculated on the most obstructed side, and that airflow, nasal resistance, and heat flux were significantly changed bilaterally as well. Moderate linear correlations with patient-reported symptoms were found for airflow, heat flux, unilateral allocation of airflow, and unilateral nasal resistance as a fraction of bilateral nasal resistance when calculated on the most obstructed nasal side, suggesting that these variables may be useful for evaluating the efficacy of nasal surgery objectively. Similarity in the strengths of these correlations suggests that patient-reported symptoms may represent a constellation of effects and that these variables should be tracked concurrently during future virtual surgery planning. © 2013 Elsevier Ltd. All rights reserved.

  6. Lactococci and lactobacilli as mucosal delivery vectors for therapeutic proteins and DNA vaccines

    PubMed Central

    2011-01-01

    Food-grade Lactic Acid Bacteria (LAB) have been safely consumed for centuries by humans in fermented foods. Thus, they are good candidates to develop novel oral vectors, constituting attractive alternatives to attenuated pathogens, for mucosal delivery strategies. Herein, this review summarizes our research, up until now, on the use of LAB as mucosal delivery vectors for therapeutic proteins and DNA vaccines. Most of our work has been based on the model LAB Lactococcus lactis, for which we have developed efficient genetic tools, including expression signals and host strains, for the heterologous expression of therapeutic proteins such as antigens, cytokines and enzymes. Resulting recombinant lactococci strains have been tested successfully for their prophylactic and therapeutic effects in different animal models: i) against human papillomavirus type 16 (HPV-16)-induced tumors in mice, ii) to partially prevent a bovine β-lactoglobulin (BLG)-allergic reaction in mice and iii) to regulate body weight and food consumption in obese mice. Strikingly, all of these tools have been successfully transposed to the Lactobacillus genus, in recent years, within our laboratory. Notably, anti-oxidative Lactobacillus casei strains were constructed and tested in two chemically-induced colitis models. In parallel, we also developed a strategy based on the use of L. lactis to deliver DNA at the mucosal level, and were able to show that L. lactis is able to modulate the host response through DNA delivery. Today, we consider that all of our consistent data, together with those obtained by other groups, demonstrate and reinforce the interest of using LAB, particularly lactococci and lactobacilli strains, to develop novel therapeutic protein mucosal delivery vectors which should be tested now in human clinical trials. PMID:21995317

  7. Flying vaccinator; a transgenic mosquito delivers a Leishmania vaccine via blood feeding.

    PubMed

    Yamamoto, D S; Nagumo, H; Yoshida, S

    2010-06-01

    'Flying vaccinator' is the concept of using genetically engineered hematophagous insects to deliver vaccines. Here we show the generation of a transgenic anopheline mosquito that expresses the Leishmania vaccine candidate, SP15, fused to monomeric red fluorescent protein (mDsRed) in its salivary glands. Importantly, mice bitten repeatedly by the transgenic mosquitoes raised anti-SP15 antibodies, indicating delivery of SP15 via blood feeding with its immunogenicity intact. Thus, this technology makes possible the generation of transgenic mosquitoes that match the original concept of a 'flying vaccinator'. However, medical safety issues and concerns about informed consent mitigate the use of the 'flying vaccinator' as a method to deliver vaccines. We propose that this expression system could be applied to elucidate saliva-malaria sporozoite interactions.

  8. Effect of Deviated Nasal Septum Type on Nasal Mucociliary Clearance, Olfactory Function, Quality of Life, and Efficiency of Nasal Surgery.

    PubMed

    Berkiten, Güler; Kumral, Tolgar Lütfi; Saltürk, Ziya; Atar, Yavuz; Yildirim, Güven; Uyar, Yavuz; Aydoğdu, Imran; Arslanoğlu, Ahmet

    2016-07-01

    The aim of this study was to analyze the influence of deviated nasal septum (DNS) type on nasal mucociliary clearance, quality of life (QoL), olfactory function, and efficiency of nasal surgery (septoplasty with or without inferior turbinate reduction and partial middle turbinectomy). Fifty patients (20 females and 30 males) with septal deviation were included in the study and were divided into 6 groups according to deviation type after examination by nasal endoscopy and paranasal computed tomography. The saccharin clearance test to evaluate the nasal mucociliary clearance time, Connecticut Chemosensory Clinical Research Center smell test for olfactory function, and sinonasal outcome test-22 (SNOT-22) for patient satisfaction were applied preoperatively and postoperatively at the sixth week after surgery. Nasal mucociliary clearance, smell, and SNOT-22 scores were measured before surgery and at the sixth week following surgery. No significant difference was found in olfactory and SNOT-22 scores for any of the DNS types (both convex and concave sides) (P > 0.05). In addition, there was no difference in the saccharin clearance time (SCT) of the concave and convex sides (P > 0.05). According to the DNS type, the mean SCT of the convex sides showed no difference, but that of the concave sides showed a difference in types 3, 4, 5, and 6. These types had a prolonged SCT (P < 0.05). Olfactory scores revealed no difference postoperatively in types 5 and 6 but were decreased significantly in types 1 to 4 (P < 0.05). There was no significant difference in the healing of both the mucociliary clearance (MCC) and olfactory functions. SNOT-22 results showed a significant decrease in type 3. All DNS types disturb the QoL regarding nasal MCC and olfaction functions. MCC values, olfactory function, and QoL scores are similar among the DNS types. Both sides of the DNS types affect the MCC scores symmetrically. Septal surgery improves olfaction function and QoL at the

  9. Enhanced Analgesic Responses After Preferential Delivery of Morphine and Fentanyl to the Olfactory Epithelium in Rats

    PubMed Central

    Hoekman, John D.; Ho, Rodney J.Y.

    2011-01-01

    Background Centrally acting opioid analgesics such as morphine and fentanyl are effective, but their efficacy is often limited by a delayed response or side effects resulting from systemic first-pass before reaching the brain and the central nervous system (CNS). It is generally accepted that drugs applied to the nasal cavity can directly access the brain and the CNS, which could provide therapeutic advantages such as rapid onset and lower systemic exposure. The olfactory region of the nasal cavity has been implicated in facilitating this direct nose-to-CNS transfer. If the fraction of opioid administered to the olfactory region could be improved, there could be a larger fraction of drug directly delivered to the CNS, mediating greater therapeutic benefit. Methods We have developed a pressurized olfactory delivery (POD) device to consistently and non-invasively deposit a majority of drug on the olfactory region of the nasal cavity in Sprague-Dawley rats. Using the tail-flick latency test and analysis of plasma and CNS tissue drug exposure, we compared distribution and efficacy of the opioids morphine and fentanyl administered to the nasal olfactory region with the POD device or the nasal respiratory region with nose drops or systemically via intraperitoneal (IP) injection. Results Compared to nose drop, POD administration of morphine resulted in significantly higher overall therapeutic effect (AUCeffect) without a significant increase in plasma drug exposure (AUCplasma). POD delivery of morphine resulted in a nose-to-CNS direct transport percentage of 38–55%. POD delivery of fentanyl led to a faster (5 min vs. 10 min) and more intense analgesic effect compared to nasal respiratory administration. Unlike IP injection or nose drop administration, both morphine and fentanyl given by the POD device to olfactory nasal epithelium exhibited clockwise [plasma] versus effect hysteresis after nasal POD administration, consistent with direct nose-to-CNS drug transport

  10. Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity.

    PubMed

    Zhang, Rui; Kramer, Jake S; Smith, Josiah D; Allen, Brittany N; Leeper, Caitlin N; Li, Xiaolei; Morton, Logan D; Gallazzi, Fabio; Ulery, Bret D

    2018-06-01

    Current vaccine research has shifted from traditional vaccines (i.e., whole-killed or live-attenuated) to subunit vaccines (i.e., protein, peptide, or DNA) as the latter is much safer due to delivering only the bioactive components necessary to produce a desirable immune response. Unfortunately, subunit vaccines are very weak immunogens requiring delivery vehicles and the addition of immunostimulatory molecules termed adjuvants to convey protective immunity. An interesting type of delivery vehicle is peptide amphiphile micelles (PAMs), unique biomaterials where the vaccine is part of the nanomaterial itself. Due to the modularity of PAMs, they can be readily modified to deliver both vaccine antigens and adjuvants within a singular construct. Through the co-delivery of a model antigenic epitope (Ovalbumin 319-340 -OVA BT ) and a known molecular adjuvant (e.g., 2,3-dipalmitoyl-S-glyceryl cysteine-Pam 2 C), greater insight into the mechanisms by which PAMs can exert immunostimulatory effects was gained. It was found that specific combinations of antigen and adjuvant can significantly alter vaccine immunogenicity both in vitro and in vivo. These results inform fundamental design rules that can be leveraged to fabricate optimal PAM-based vaccine formulations for future disease-specific applications. Graphical Abstract.

  11. BCG vaccination in England since 2005: a survey of policy and practice.

    PubMed

    Pilger, Daniel; Nguipdop-Djomo, Patrick; Abubakar, Ibrahim; Elliman, David; Rodrigues, Laura C; Watson, John M; Eastman, Vera; Mangtani, Punam

    2012-01-01

    Assess the current BCG vaccination policies and delivery pathways for immunisation in Primary Care Trusts (PCTs) in England since the 2005 change in recommendations. A survey of key informants across PCTs using a standardised, structured questionnaire. 152 PCTs in England. Complete questionnaires were returned from 127 (84%) PCTs. Sixteen (27%) PCTs reported universal infant vaccination and 111 (73%) had selective infant vaccination. Selective vaccination outside infancy was also reported from 94 (74%) PCTs. PCTs with selective infant policy most frequently vaccinated on postnatal wards (51/102, 50%), whereas PCTs with universal infant vaccination most frequently vaccinated in community clinics (9/13, 69%; p=0.011). To identify and flag up eligible infants in PCTs with targeted infant immunisation, those who mostly vaccinate on postnatal wards depend on midwives and maternity records, whereas those who vaccinate primarily in the community rely more often on various healthcare professionals. Targeted infant vaccination has been implemented in most PCTs across the UK. PCTs with selective infant vaccination provide BCG vaccine via a greater variety of healthcare professionals than those with universal infant vaccination policies. Data on vaccine coverage would help evaluate the effectiveness of delivery. Interruptions of delivery noted here emphasise the importance of not just an agreed, standardised, local pathway, but also a named person in charge.

  12. Vaccine process technology.

    PubMed

    Josefsberg, Jessica O; Buckland, Barry

    2012-06-01

    The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory

  13. Intranasal hydrocodone-acetaminophen abuse induced necrosis of the nasal cavity and pharynx.

    PubMed

    Alexander, David; Alexander, Keith; Valentino, Joseph

    2012-11-01

    Two million new users will abuse prescription narcotics this year, most commonly hydrocodone. The most commonly prescribed form is hydrocodone-acetaminophen (HA). Many individuals crush the tablets and snort the product to take advantage of the rapid transmucosal delivery of narcotics. The resultant pathology of intranasal hydrocodone acetaminophen abuse (INHAA) has been described only in a few case studies. Retrospective chart review. Two private and one academic otolaryngology practices in Kentucky searched their patient charts for patients with morbidity from intranasal abuse of hydrocodone acetaminophen tablets. We identified thirty-five patients who presented for treatment between 2004 and 2011. The majority of patients will initially deny the behavior, frequently delaying diagnosis. Physical exam findings of white powder covering an underlying nasal mucosal necrosis are characteristic of this condition during active INHAA. Follow up was limited as only 26% returned for follow-up care. Patients commonly presented with orofacial-nasal pain (43%) and sino-nasal congestion and discharge (43%). Active necrosis or prior tissue loss was noted in 77% of patients. Fifty-one percent of patients presented with septal perforations, and 26% with palatal perforations. Two cases of invasive fungal sinusitis were clearly documented, with one resulting in death. The vast majority of cases presented with characteristic physical findings that included acute necrosis of soft tissue, which can progress to destroy oronasal structures. In the absence of invasive fungal disease, the condition is self-limited after cessation of INHAA and performance of local nasal debridement and nasal hygiene. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  14. Noninvasive delivery systems for peptides and proteins in osteoporosis therapy: a retroperspective.

    PubMed

    Hoyer, Herbert; Perera, Glen; Bernkop-Schnürch, Andreas

    2010-01-01

    The aim of this review is to provide the reader general and inspiring prospects in various attempts to make noninvasive delivery systems of calcitonin and teriparatide feasible and as convenient as possible. Calcitonin and teriparatide play an important role in both calcium homeostasis and bone remodelling. Currently calcitonin is available as a subcutaneous injection and as a nasal spray whereas teriparatide is administered subcutaneously. In the past few years, an increasing number of articles about drug delivery systems for calcitonin and teriparatide have been published. These delivery systems have been developed to overcome the inherent barriers for the uptake across the diverse membranes on the various routes for protein and peptide delivery. Co-administration of permeation enhancers, mucoadhesive agents, viscosity modifying agents, multifunctional polymers, protease inhibitors as well as encapsulation and chemical modification are utilized in order to improve calcitonin and teriparatide absorption after oral, nasal, pulmonal, or buccal administration. The majority of research groups have been working on the development of formulations based on the encapsulation of molecules in biodegradable and biocompatible polymeric nanoparticles. However these observations are based on data obtained under different experimental conditions. Hence, it is difficult to compare the obtained results in order to draw general conclusions about the most promising characteristics required for oral and nasal formulations for these peptides.

  15. Applications and challenges of multivalent recombinant vaccines

    PubMed Central

    Naim, Hussein Y.

    2013-01-01

    The exceptional discoveries of antigen/gene delivery systems have allowed the development of novel prophylactic and therapeutic vaccine candidates. The vaccine candidates employ various antigen-delivery systems, particularly recombinant viral vectors. Recombinant viral vectors are experimental vaccines similar to DNA vaccines, but they use attenuated viruses or bacterium as a carrier “vector” to introduce microbial DNA to cells of the body. They closely mimic a natural infection and therefore can efficiently stimulate the immune system. Although such recombinant vectors may face extensive preclinical testing and will possibly have to meet stringent regulatory requirements, some of these vectors (e.g. measles virus vectors) may benefit from the profound industrial and clinical experience of the parent vaccine. Most notably, novel vaccines based on live attenuated viruses combine the induction of broad, strong and persistent immune responses with acceptable safety profiles. We assess certain technologies in light of their use against human immunodeficiency virus (HIV). PMID:23249651

  16. Vaccination against bubonic and pneumonic plague.

    PubMed

    Titball, R W; Williamson, E D

    2001-07-20

    Yersinia pestis is the etiological agent of bubonic and pneumonic plague, diseases which have caused over 200 milllion human deaths in the past. Plague still occurs throughout the world today, though for reasons that are not fully understood pandemics of disease do not develop from these outbreaks. Antibiotic treatment of bubonic plague is usually effective, but pneumonic plague is difficult to treat and even with antibiotic therapy death often results. A killed whole cell plague vaccine has been used in the past, but recent studies in animals have shown that this vaccine offers poor protection against pneumonic disease. A live attenuated vaccine is also available. Whilst this vaccine is effective, it retains some virulence and in most countries it is not considered to be suitable for use in humans. We review here work to develop improved sub-unit and live attenuated vaccines against plague. A sub-unit vaccine based on the F1- and V-antigens is highly effective against both bubonic and pneumonic plague, when tested in animal models of disease. This vaccine has been used to explore the utility of different intranasal and oral delivery systems, based on the microencapsulation or Salmonella delivery of sub-units.

  17. Beyond empiricism: Informing vaccine development through innate immunity research

    PubMed Central

    Levitz, Stuart M.; Golenbock, Douglas T.

    2012-01-01

    Summary While a great public heath success, vaccines provide suboptimal protection in some patient populations and are not available to protect against many infectious diseases. Insights from innate immunity research have led to a better understanding of how existing vaccines work and informed vaccine development. New adjuvants and delivery systems are being designed based upon their capacity to stimulate innate immune sensors and target antigens to dendritic cells, the cells responsible for initiating adaptive immune responses. Incorporating these adjuvants and delivery systems in vaccines can beneficially alter the quantitative and qualitative nature of the adaptive immune response resulting in enhanced protection. PMID:22424235

  18. Cosmetic and Functional Nasal Deformities

    MedlinePlus

    ... nasal complaints. Nasal deformity can be categorized as “cosmetic” or “functional.” Cosmetic deformity of the nose results in a less ... taste , nose bleeds and/or recurrent sinusitis . A cosmetic or functional nasal deformity may occur secondary to ...

  19. Cosmetic rostral nasal reconstruction after nasal planum and premaxilla resection: technique and results in two dogs.

    PubMed

    Gallegos, Javier; Schmiedt, Chad W; McAnulty, Jonathan F

    2007-10-01

    To describe a novel reconstructive technique after nasal planum and premaxilla resection. Case report. Dogs (n=2) with squamous cell carcinoma (SCC) of the nasal planum. A 9-year-old neutered female Labrador retriever (dog 1) and an 11-year-old neutered male Golden retriever (dog 2) had resection of the nasal planum and premaxilla for treatment of locally invasive SCC. Reconstruction of a nasal planum facsimile was based on use of the nonhaired pigmented margins of bilateral labial mucocutaneous rotation-advancement flaps. Reconstruction of the premaxilla by construction of a nasal planum facsimile resulted in uncomplicated wound healing and improved cosmesis. There was no tumor recurrence at 1290 (dog 1) and 210 (dog 2) days after surgery. Reconstruction of a nasal planum facsimile was successfully performed without complications in 2 dogs with high owner satisfaction with cosmetic appearance. This technique represents a significant advancement in surgical cosmetic outcome, may potentially reduce postoperative complications, and should be considered for dogs requiring nasal reconstruction after nasal planum resection with premaxillectomy.

  20. A cost comparison of introducing and delivering pneumococcal, rotavirus and human papillomavirus vaccines in Rwanda.

    PubMed

    Ngabo, Fidèle; Levin, Ann; Wang, Susan A; Gatera, Maurice; Rugambwa, Celse; Kayonga, Celestin; Donnen, Philippe; Lepage, Philippe; Hutubessy, Raymond

    2015-12-16

    Detailed cost evaluations of delivery of new vaccines such as pneumococcal conjugate, human papillomavirus (HPV), and rotavirus vaccines in low and middle-income countries are scarce. This paper differs from others by comparing the costs of introducing multiple vaccines in a single country and then assessing the financial and economic impact at the time and implications for the future. The objective of the analysis was to understand the introduction and delivery cost per dose or per child of the three new vaccines in Rwanda to inform domestic and external financial resource mobilization. Start-up, recurrent, and capital costs from a government perspective were collected in 2012. Since pneumococcal conjugate and HPV vaccines had already been introduced, cost data for those vaccines were collected retrospectively while prospective (projected) costing was done for rotavirus vaccine. The financial unit cost per fully immunized child (or girl for HPV vaccine) of delivering 3 doses of each vaccine (without costs related to vaccine procurement) was $0.37 for rotavirus (RotaTeq(®)) vaccine, $0.54 for pneumococcal (Prevnar(®)) vaccine in pre-filled syringes, and $10.23 for HPV (Gardasil (®)) vaccine. The financial delivery costs of Prevnar(®) and RotaTeq(®) were similar since both were delivered using existing health system infrastructure to deliver infant vaccines at health centers. The total financial cost of delivering Gardasil(®) was higher than those of the two infant vaccines due to greater resource requirements associated with creating a new vaccine delivery system in for a new target population of 12-year-old girls who have not previously been served by the existing routine infant immunization program. The analysis indicates that service delivery strategies have an important influence on costs of introducing new vaccines and costs per girl reached with HPV vaccine are higher than the other two vaccines because of its delivery strategy. Documented information

  1. CPAP and High-Flow Nasal Cannula Oxygen in Bronchiolitis.

    PubMed

    Sinha, Ian P; McBride, Antonia K S; Smith, Rachel; Fernandes, Ricardo M

    2015-09-01

    Severe respiratory failure develops in some infants with bronchiolitis because of a complex pathophysiologic process involving increased airways resistance, alveolar atelectasis, muscle fatigue, and hypoxemia due to mismatch between ventilation and perfusion. Nasal CPAP and high-flow nasal cannula (HFNC) oxygen may improve the work of breathing and oxygenation. Although the mechanisms behind these noninvasive modalities of respiratory support are not well understood, they may help infants by way of distending pressure and delivery of high concentrations of warmed and humidified oxygen. Observational studies of varying quality have suggested that CPAP and HFNC may confer direct physiologic benefits to infants with bronchiolitis and that their use has reduced the need for intubation. No trials to our knowledge, however, have compared CPAP with HFNC in bronchiolitis. Two randomized trials compared CPAP with oxygen delivered by low-flow nasal cannula or face mask and found some improvements in blood gas results and some physiologic parameters, but these trials were unable to demonstrate a reduction in the need for intubation. Two trials evaluated HFNC in bronchiolitis (one comparing it with headbox oxygen, the other with nebulized hypertonic saline), with the results not seeming to suggest important clinical or physiologic benefits. In this article, we review the pathophysiology of respiratory failure in bronchiolitis, discuss these trials in detail, and consider how future research studies may be designed to best evaluate CPAP and HFNC in bronchiolitis.

  2. Risk factors for nasal malignancies in German men: the South-German Nasal cancer study.

    PubMed

    Greiser, Eberhard M; Greiser, Karin Halina; Ahrens, Wolfgang; Hagen, Rudolf; Lazszig, Roland; Maier, Heinz; Schick, Bernhard; Zenner, Hans Peter

    2012-11-06

    There are few studies of the effects of nasal snuff and environmental factors on the risk of nasal cancer. This study aimed to investigate the impact of using nasal snuff and of other risk factors on the risk of nasal cancer in German men. A population-based case-control study was conducted in the German Federal States of Bavaria and Baden-Württemberg. Tumor registries and ear, nose and throat departments provided access to patients born in 1926 or later. Telephone interviews were conducted with 427 cases (mean age 62.1 years) and 2.401 population-based controls (mean age 60.8 years). Ever-use of nasal snuff was associated with an odds ratio (OR) for nasal cancer of 1.45 (95% confidence interval [CI] 0.88-2.38) in the total study population, whereas OR in smokers was 2.01 (95% CI 1.00-4.02) and in never smokers was 1.10 (95% CI 0.43-2.80). The OR in ever-smokers vs. never-smokers was 1.60 (95% CI 1.24-2.07), with an OR of 1.06 (95% CI 1.05-1.07) per pack-year smoked, and the risk was significantly decreased after quitting smoking. Exposure to hardwood dust for at least 1 year resulted in an OR of 2.33 (95% CI 1.40-3.91) in the total population, which was further increased in never-smokers (OR 4.89, 95% CI 1.92-12.49) in analyses stratified by smoking status. The OR for nasal cancer after exposure to organic solvents for at least 1 year was 1.53 (1.17-2.01). Ever-use of nasal sprays/nasal lavage for at least 1 month rendered an OR of 1.59 (1.04-2.44). The OR after use of insecticides in homes was 1.48 (95% CI 1.04-2.11). Smoking and exposure to hardwood dust were confirmed as risk factors for nasal carcinoma. There is evidence that exposure to organic solvents, and in-house use of insecticides could represent novel risk factors. Exposure to asbestos and use of nasal snuff were risk factors in smokers only.

  3. Nasal obstruction and human communication.

    PubMed

    Malinoff, R; Moreno, C

    1989-04-01

    Nasal obstruction may cause a variety of communication disorders, particularly in children. The effects of nasal obstruction on hearing, speech, language, and voice are examined. Methods for assessing the effects of nasal obstruction are delineated, and recommendations for therapeutic interventions are described.

  4. Footrot vaccines and vaccination.

    PubMed

    Dhungyel, Om; Hunter, James; Whittington, Richard

    2014-05-30

    Research on footrot in small ruminants, which is caused by Dichelobacter nodosus, has led to development of vaccines and their application for control, treatment and eradication of the disease in sheep. Footrot vaccines have evolved over decades to contain monovalent whole cell, multivalent recombinant fimbrial, and finally mono or bivalent recombinant fimbrial antigens. Initially whole cell vaccines made against the few known serogroups of D. nodosus were found to be inefficient in control of the disease in the field, which was attributed to the presence of other unidentified serogroups and also the use of inefficient adjuvants. Fimbriae or pili, which are the basis for antigenic variation, were found to be the major protective and also curative antigens but they are not cross protective between the different serogroups. Multivalent vaccines incorporating all the known serogroups have been proven to be of limited efficacy due to the phenomenon of antigenic competition. Recent studies in Nepal, Bhutan and Australia have shown that outbreak-specific vaccination which involves targeting identified serogroups with mono- or bivalent recombinant fimbrial vaccines, can be very effective in sheep and goats. Where multiple serogroups are present in a flock, antigenic competition can be overcome by sequentially targeting the serogroups with different bivalent vaccines every 3 months. A common antigen which would confer immunity to all serogroups would be the ideal immunogen but the initial studies were not successful in this area. Until universal antigen/s are available, flock specific mono or bivalent fimbrial vaccines are likely to be the most effective tool for control and eradication of footrot in sheep and goats. Future research in footrot vaccines should be focused on improving the duration of prophylaxis by incorporating new and emerging immunomodulators or adjuvants with modified delivery vehicles, discovering a common antigen and understanding the mechanisms of

  5. Nasal masks or binasal prongs for delivering continuous positive airway pressure in preterm neonates-a randomised trial.

    PubMed

    Chandrasekaran, Aparna; Thukral, Anu; Jeeva Sankar, M; Agarwal, Ramesh; Paul, Vinod K; Deorari, Ashok K

    2017-03-01

    The objective of this study was to compare the efficacy and safety of continuous positive airway pressure (CPAP) delivered using nasal masks with binasal prongs. We randomly allocated 72 neonates between 26 and 32 weeks gestation to receive bubble CPAP by either nasal mask (n = 37) or short binasal prongs (n = 35). Primary outcome was mean FiO 2 requirement at 6, 12 and 24 h of CPAP initiation and the area under curve (AUC) of FiO 2 against time during the first 24 h (FiO 2 AUC 0-24 ). Secondary outcomes were the incidence of CPAP failure and nasal trauma. FiO 2 requirement at 6, 12 and 24 h (mean (SD); 25 (5.8) vs. 27.9 (8); 23.8 (4.5) vs. 25.4 (6.8) and 22.6 (6.8) vs. 22.7 (3.3)) as well as FiO 2 AUC 0-24 (584.0 (117.8) vs. 610.6 (123.6)) were similar between the groups. There was no difference in the incidence of CPAP failure (14 vs. 20%; relative risk 0.67; 95% confidence interval 0.24-1.93). Incidence of severe nasal trauma was lower with the use of nasal masks (0 vs. 31%; p < .001). Nasal masks appear to be as efficacious as binasal prongs in providing CPAP. Masks are associated with lower risk of severe nasal trauma. CTRI2012/08/002868 What is Known? • Binasal prongs are better than single nasal and nasopharyngeal prongs for delivering continuous positive airway pressure (CPAP) in preventing need for re-intubation. • It is unclear if they are superior to newer generation nasal masks in preterm neonates requiring CPAP. What is New? • Oxygen requirement during the first 24 h of CPAP delivery is comparable with use of nasal masks and binasal prongs. • Use of nasal masks is, however, associated with significantly lower risk of severe grades of nasal injury.

  6. Intradermal inactivated poliovirus vaccine: a preclinical dose-finding study.

    PubMed

    Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin

    2015-05-01

    Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial vaccine doses induced antibodies at titers comparable to those after immunization with full human dose delivered intramuscularly. The results suggest that intradermal delivery of IPV may lead to dose-sparing effect and reduction of the vaccination cost. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  7. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... nasal airflow. The device decreases airway resistance and increases nasal airflow. The external nasal...

  8. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... nasal airflow. The device decreases airway resistance and increases nasal airflow. The external nasal...

  9. Efficient Nose-to-Lung (N2L) Aerosol Delivery with a Dry Powder Inhaler

    PubMed Central

    Golshahi, Laleh; Behara, Srinivas R.B.; Tian, Geng; Farkas, Dale R.; Hindle, Michael

    2015-01-01

    Abstract Purpose: Delivering aerosols to the lungs through the nasal route has a number of advantages, but its use has been limited by high depositional loss in the extrathoracic airways. The objective of this study was to evaluate the nose-to-lung (N2L) delivery of excipient enhanced growth (EEG) formulation aerosols generated with a new inline dry powder inhaler (DPI). The device was also adapted to enable aerosol delivery to a patient simultaneously receiving respiratory support from high flow nasal cannula (HFNC) therapy. Methods: The inhaler delivered the antibiotic ciprofloxacin, which was formulated as submicrometer combination particles containing a hygroscopic excipient prepared by spray-drying. Nose-to-lung delivery was assessed using in vitro and computational fluid dynamics (CFD) methods in an airway model that continued through the upper tracheobronchial region. Results: The best performing device contained a 2.3 mm flow control orifice and a 3D rod array with a 3-4-3 rod pattern. Based on in vitro experiments, the emitted dose from the streamlined nasal cannula had a fine particle fraction <5 μm of 95.9% and mass median aerodynamic diameter of 1.4 μm, which was considered ideal for nose-to-lung EEG delivery. With the 2.3-343 device, condensational growth in the airways increased the aerosol size to 2.5–2.7 μm and extrathoracic deposition was <10%. CFD results closely matched the in vitro experiments and predicted that nasal deposition was <2%. Conclusions: The developed DPI produced high efficiency aerosolization with significant size increase of the aerosol within the airways that can be used to enable nose-to-lung delivery and aerosol administration during HFNC therapy. PMID:25192072

  10. A dendritic cell targeted vaccine induces long-term HIV-specific immunity within the gastrointestinal tract.

    PubMed

    Ruane, D; Do, Y; Brane, L; Garg, A; Bozzacco, L; Kraus, T; Caskey, M; Salazar, A; Trumpheller, C; Mehandru, S

    2016-09-01

    Despite significant therapeutic advances for HIV-1 infected individuals, a preventative HIV-1 vaccine remains elusive. Studies focusing on early transmission events, including the observation that there is a profound loss of gastrointestinal (GI) CD4(+) T cells during acute HIV-1 infection, highlight the importance of inducing HIV-specific immunity within the gut. Here we report on the generation of cellular and humoral immune responses in the intestines by a mucosally administered, dendritic cell (DC) targeted vaccine. Our results show that nasally delivered α-CD205-p24 vaccine in combination with polyICLC, induced polyfunctional immune responses within naso-pulmonary lymphoid sites that disseminated widely to systemic and mucosal (GI tract and the vaginal epithelium) sites. Qualitatively, while α-CD205-p24 prime-boost immunization generated CD4(+) T-cell responses, heterologous prime-boost immunization with α-CD205-p24 and NYVAC gag-p24 generated high levels of HIV-specific CD4(+) and CD8(+) T cells within the GI tract. Finally, DC-targeting enhanced the amplitude and longevity of vaccine-induced immune responses in the GI tract. This is the first report of a nasally delivered, DC-targeted vaccine to generate HIV-specific immune responses in the GI tract and will potentially inform the design of preventative approaches against HIV-1 and other mucosal infections.

  11. Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs

    PubMed Central

    Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A.; Thörn, Karolina; Cairns, Tina M.; Wegmann, Frank; Sattentau, Quentin J.; Eisenberg, Roselyn J.; Cohen, Gary H.; Harandi, Ali M.

    2016-01-01

    Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes. PMID:28082979

  12. Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs.

    PubMed

    Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A; Thörn, Karolina; Cairns, Tina M; Wegmann, Frank; Sattentau, Quentin J; Eisenberg, Roselyn J; Cohen, Gary H; Harandi, Ali M

    2016-01-01

    Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes.

  13. Chitosan

    PubMed Central

    Smith, Alan; Perelman, Michael; Hinchcliffe, Michael

    2014-01-01

    The nasal route is attractive for the delivery of vaccines in that it not only offers an easy to use, non-invasive, needle-free alternative to more conventional parenteral injection, but it also creates an opportunity to elicit both systemic and (crucially) mucosal immune responses which may increase the capability of controlling pathogens at the site of entry. Immune responses to “naked” antigens are often modest and it is widely accepted that incorporation of an adjuvant is a prerequisite for the achievement of clinically effective nasal vaccines. Many existing adjuvants are sub-optimal or unsuitable because of local toxicity or poor enhancement of immunogenicity. Chitosan, particularly chitosan salts, have now been used in several preclinical and clinical studies with good tolerability, excellent immune stimulation and positive clinical results across a number of infections. Particularly significant evidence supporting chitosan as an adjuvant for nasal vaccination comes from clinical investigations on a norovirus vaccine; this demonstrated the ability of chitosan (ChiSys®), when combined with monophosphoryl lipid, to evoke robust immunological responses and confer protective immunity following (enteral) norovirus challenge. This article summarizes the totality of the meaningful information (including key unpublished data) supporting the development of chitosan-adjuvanted vaccines. PMID:24346613

  14. [Nasal septal abscess].

    PubMed

    Barril, María F; Ferolla, Fausto M; José, Pablo; Echave, Cecilia; Tomezzoli, Silvana; Fiorini, Sandra; López, Eduardo Luis

    2008-12-01

    A nasal septal abscess (NA) is defined as a collection of pus between the cartilage or bony septum and its normally applied mucoperichondrium or mucoperiostium. It is an uncommon disease which should be suspected in a patient with acute onset of nasal obstruction and recent history of nasal trauma, periodontal infection or an inflammatory process of the rhinosinusal region. We report a case of an 8-year-old boy with bilateral NA caused by community-acquired methicillin-resistant Staphylococcus aureus(MR-CO) in order to emphasize the importance of prompt diagnosis and adequate treatment to prevent the potentially dangerous spread of infection and the development of severe functional and cosmetic sequelae.

  15. BCG vaccination in England since 2005: a survey of policy and practice

    PubMed Central

    Pilger, Daniel; Nguipdop-Djomo, Patrick; Abubakar, Ibrahim; Elliman, David; Rodrigues, Laura C; Watson, John M; Eastman, Vera; Mangtani, Punam

    2012-01-01

    Objective Assess the current BCG vaccination policies and delivery pathways for immunisation in Primary Care Trusts (PCTs) in England since the 2005 change in recommendations. Design A survey of key informants across PCTs using a standardised, structured questionnaire. Setting 152 PCTs in England. Results Complete questionnaires were returned from 127 (84%) PCTs. Sixteen (27%) PCTs reported universal infant vaccination and 111 (73%) had selective infant vaccination. Selective vaccination outside infancy was also reported from 94 (74%) PCTs. PCTs with selective infant policy most frequently vaccinated on postnatal wards (51/102, 50%), whereas PCTs with universal infant vaccination most frequently vaccinated in community clinics (9/13, 69%; p=0.011). To identify and flag up eligible infants in PCTs with targeted infant immunisation, those who mostly vaccinate on postnatal wards depend on midwives and maternity records, whereas those who vaccinate primarily in the community rely more often on various healthcare professionals. Conclusions Targeted infant vaccination has been implemented in most PCTs across the UK. PCTs with selective infant vaccination provide BCG vaccine via a greater variety of healthcare professionals than those with universal infant vaccination policies. Data on vaccine coverage would help evaluate the effectiveness of delivery. Interruptions of delivery noted here emphasise the importance of not just an agreed, standardised, local pathway, but also a named person in charge. PMID:22964115

  16. Preparation and characterization of protein-loaded poly(epsilon-caprolactone) microparticles for oral vaccine delivery.

    PubMed

    Benoit, M A; Baras, B; Gillard, J

    1999-07-05

    This paper describes the conditions of preparation of poly(epsilon-caprolactone) (PCL) microparticles with a mean size between 5 and 10 microm, obtained by a double emulsion-solvent evaporation technique, suitable for oral vaccine delivery. Bovine serum albumin (BSA) was used as water-soluble model antigen for encapsulation. Different parameters influencing the microparticle size, the BSA loading and entrapment efficiency were investigated. Spherical, smooth and homogeneously distributed microparticles were produced with a BSA loading and entrapment efficiency reaching, respectively, 5% (w/w) and 30%. Polyacrylamide gel electrophoresis (PAGE) and isoelectric focusing (IEF) analyses of BSA released from these particles confirmed that the entrapped protein seemed to remain unaltered by the protein encapsulation process. Copyright.

  17. Analytical challenges and regulatory requirements for nasal drug products in europe and the u.s.

    PubMed

    Trows, Sabrina; Wuchner, Klaus; Spycher, Rene; Steckel, Hartwig

    2014-04-11

    Nasal drug delivery can be assessed by a variety of means and regulatory agencies, e.g., the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published a set of guidelines and regulations proposing in vitro test methods for the characterization of nasal drug products. This article gives a summary of the FDA and EMA requirements regarding the determination of droplet size distribution (DSD), plume geometry, spray pattern and shot weights of solution nasal sprays and discusses the analytical challenges that can occur when performing these measurements. In order to support findings from the literature, studies were performed using a standard nasal spray pump and aqueous model formulations. The aim was to identify possible method-, device- and formulation-dependent influencing factors. The literature review, as well as the results from the studies show that DSD, plume geometry and spray pattern are influenced by, e.g., the viscosity of the solution, the design of the device and the actuation parameters, particularly the stroke length, actuation velocity and actuation force. The dominant factor influencing shot weights, however, is the adjustment of the actuation parameters, especially stroke length and actuation velocity. Consequently, for routine measurements assuring, e.g., the quality of a solution nasal spray or, for in vitro bioequivalence studies, the critical parameters, have to be identified and considered in method development in order to obtain reproducible and reliable results.

  18. Membrane-bound IL-12 and IL-23 serve as potent mucosal adjuvants when co-presented on whole inactivated influenza vaccines.

    PubMed

    Khan, Tila; Heffron, Connie L; High, Kevin P; Roberts, Paul C

    2014-05-03

    Potent and safe adjuvants are needed to improve the efficacy of parenteral and mucosal vaccines. Cytokines, chemokines and growth factors have all proven to be effective immunomodulatory adjuvants when administered with a variety of antigens. We have previously evaluated the efficacy of membrane-anchored interleukins (IL) such as IL-2 and IL-4 co-presented as Cytokine-bearing Influenza Vaccines (CYT-IVACs) using a mouse model of influenza challenge. Here, we describe studies evaluating the parenteral and mucosal adjuvanticity of membrane-bound IL-12 and IL-23 CYT-IVACs in young adult mice. Mucosal immunization using IL-12 and IL-23 bearing whole influenza virus vaccine (WIV) was more effective at eliciting virus-specific nasal IgA and reducing viral lung burden following challenge compared to control WIV vaccinated animals. Both IL-12 and IL-23 bearing WIV elicited the highest anti-viral IgA levels in serum and nasal washes. This study highlights for the first time the mucosal adjuvant potential of IL-12 and IL-23 CYT-IVAC formulations in eliciting mucosal immune responses and reducing viral lung burden. The co-presentation of immunomodulators in direct context with viral antigen in whole inactivated viral vaccines may provide a means to significantly lower the dose of vaccine required for protection.

  19. Beyond empiricism: informing vaccine development through innate immunity research.

    PubMed

    Levitz, Stuart M; Golenbock, Douglas T

    2012-03-16

    Although a great public heath success, vaccines provide suboptimal protection in some patient populations and are not available to protect against many infectious diseases. Insights from innate immunity research have led to a better understanding of how existing vaccines work and have informed vaccine development. New adjuvants and delivery systems are being designed based upon their capacity to stimulate innate immune sensors and target antigens to dendritic cells, the cells responsible for initiating adaptive immune responses. Incorporating these adjuvants and delivery systems in vaccines can beneficially alter the quantitative and qualitative nature of the adaptive immune response, resulting in enhanced protection. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Nasal Glial Heterotopia with Cleft Palate.

    PubMed

    Chandna, Sudhir; Mehta, Milind A; Kulkarni, Abhishek Kishore

    2018-01-01

    Congenital midline nasal masses are rare anomalies of which nasal glial heterotopia represents an even rarer subset. We report a case of a 25-day-old male child with nasal glial heterotopia along with cleft palate suggesting embryonic fusion anomaly which was treated with excision and primary closure for nasal mass followed by palatal repair at later date.

  1. An Overview on the Field of Micro- and Nanotechnologies for Synthetic Peptide-Based Vaccines

    PubMed Central

    Salvador, Aiala; Igartua, Manoli; Hernández, Rosa Maria; Pedraz, José Luis

    2011-01-01

    The development of synthetic peptide-based vaccines has many advantages in comparison with vaccines based on live attenuated organisms, inactivated or killed organism, or toxins. Peptide-based vaccines cannot revert to a virulent form, allow a better conservation, and are produced more easily and safely. However, they generate a weaker immune response than other vaccines, and the inclusion of adjuvants and/or the use of vaccine delivery systems is almost always needed. Among vaccine delivery systems, micro- and nanoparticulated ones are attractive, because their particulate nature can increase cross-presentation of the peptide. In addition, they can be passively or actively targeted to antigen presenting cells. Furthermore, particulate adjuvants are able to directly activate innate immune system in vivo. Here, we summarize micro- and nanoparticulated vaccine delivery systems used in the field of synthetic peptide-based vaccines as well as strategies to increase their immunogenicity. PMID:21773041

  2. Plant-made oral vaccines against human infectious diseases—Are we there yet?

    PubMed Central

    Chan, Hui-Ting; Daniell, Henry

    2016-01-01

    Summary Although the plant-made vaccine field started three decades ago with the promise of developing low-cost vaccines to prevent infectious disease outbreaks and epidemics around the globe, this goal has not yet been achieved. Plants offer several major advantages in vaccine generation, including low-cost production by eliminating expensive fermentation and purification systems, sterile delivery and cold storage/transportation. Most importantly, oral vaccination using plant-made antigens confers both mucosal (IgA) and systemic (IgG) immunity. Studies in the past 5 years have made significant progress in expressing vaccine antigens in edible leaves (especially lettuce), processing leaves or seeds through lyophilization and achieving antigen stability and efficacy after prolonged storage at ambient temperatures. Bioencapsulation of antigens in plant cells protects them from the digestive system; the fusion of antigens to transmucosal carriers enhances efficiency of their delivery to the immune system and facilitates successful development of plant vaccines as oral boosters. However, the lack of oral priming approaches diminishes these advantages because purified antigens, cold storage/transportation and limited shelf life are still major challenges for priming with adjuvants and for antigen delivery by injection. Yet another challenge is the risk of inducing tolerance without priming the host immune system. Therefore, mechanistic aspects of these two opposing processes (antibody production or suppression) are discussed in this review. In addition, we summarize recent progress made in oral delivery of vaccine antigens expressed in plant cells via the chloroplast or nuclear genomes and potential challenges in achieving immunity against infectious diseases using cold-chain-free vaccine delivery approaches. PMID:26387509

  3. Cutaneous immunization: an evolving paradigm in influenza vaccines

    PubMed Central

    Gill, Harvinder S; Kang, Sang-Moo; Quan, Fu-Shi; Compans, Richard W

    2014-01-01

    Introduction Most vaccines are administered by intramuscular injection using a hypodermic needle and syringe. Some limitations of this procedure include reluctance to be immunized because of fear of needlesticks, and concerns associated with the safe disposal of needles after their use. Skin delivery is an alternate route of vaccination that has potential to be painless and could even lead to dose reduction of vaccines. Recently, microneedles have emerged as a novel painless approach for delivery of influenza vaccines via the skin. Areas covered In this review, we briefly summarize the approaches and devices used for skin vaccination, and then focus on studies of skin immunization with influenza vaccines using microneedles. We discuss both the functional immune response and the nature of this immune response following vaccination with microneedles. Expert opinion The cutaneous administration of influenza vaccines using microneedles offers several advantages: it is painless, elicits stronger immune responses in preclinical studies and could improve responses in high-risk populations. These dry formulations of vaccines provide enhanced stability, a property of high importance in enabling their rapid global distribution in response to possible outbreaks of pandemic influenza and newly emerging infectious diseases. PMID:24521050

  4. [Hemangiopericytoma in nasal cavity: a case report].

    PubMed

    Hu, Honghai; Shi, Qifeng; Chen, Jidong

    2015-05-01

    We report a case of a 46 year old female patient with nasal hemangiopericytoma. She complained of left nasal congestion, pus snot for 10 years, sometimes with left nasal bleeding. Physical examination: in the left nasal tract saw red soft neoplasm, roughness surface, easy bleeding when touched. Sinus CT shows: bilateral maxillary sinus, ethmoid sinus, sphenoid sinus and the left posterior nasal cavity lesions, considering inflammation with the formation of polyps, tumor not excluded. The left nasal cavity neoplasm biopsy shows: hemangioma of left nasal cavity. After admission in general anesthesia, we do transnasal endoscopic sinus openning operation and the left nasal cavity neoplasm resection. Postoperative pathological examination shows: the left nasal cavity hemangiopericytoma. Immunohistochemical showed: Vimentin(+), Smooth muscle actin(+), Desmin(-), endothelial cells CD31(-) and CD34(-). No postoperative radiotherapy or chemotherapy, no tumor recurrence. After one year of follow-up, the contact was lost.

  5. Mask versus Nasal Tube for Stabilization of Preterm Infants at Birth: Respiratory Function Measurements.

    PubMed

    van Vonderen, Jeroen J; Kamlin, C Omar; Dawson, Jennifer A; Walther, Frans J; Davis, Peter G; te Pas, Arjan B

    2015-07-01

    To compare the nasal tube with face mask as interfaces for stabilization of very preterm infants at birth by using physiological measurements of leak, obstruction, and expired tidal volumes during positive pressure ventilation (PPV). In the delivery room, 43 infants <30 weeks gestation were allocated to receive respiratory support by nasal tube or face mask. Respiratory function, heart rate, and oxygen saturation were measured. Occurrence of obstruction, amount of leak, and tidal volumes were compared using a Mann-Whitney U test or a Fisher exact test. The first 5 minutes after initiation of PPV were analyzed (1566 inflations in the nasal tube group and 1896 inflations in the face mask group). Spontaneous breathing coincided with PPV in 32% of nasal tube and 34% of face mask inflations. During inflations, higher leak was observed using nasal tube compared with face mask (98% [33%-100%] vs 14 [0%-39%]; P < .0001). Obstruction occurred more often (8.2% vs 1.1%; P < .0001). Expired tidal volumes were significantly lower during inflations when using nasal tube compared with face mask (0.0 [0.0-3.1] vs 9.9 [5.5-12.8] mL/kg; P < .0001) and when spontaneous breathing coincided with PPV (4.4 [2.1-8.4] vs 9.6 [5.4-15.2] mL/kg; P < .0001) but were similar during breathing on continuous positive airway pressure (4.7 [2.8-6.9] vs 4.8 [2.7-7.9] mL/kg; P > 0.05). Heart rate was not significantly different between groups, but oxygen saturation was significantly lower in the nasal tube group the first 2 minutes after start of respiratory support. The use of a nasal tube led to large leak, more obstruction, and inadequate tidal volumes compared with face mask. Trial registration Registered with the Dutch Trial Registry (NTR 2061) and the Australia and New Zealand Clinical Trials Register (ACTRN 12610000230055). Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Objective measurements for grading the nasal esthetics on Basal view in individuals with secondary cleft nasal deformity.

    PubMed

    He, Xing; Li, Hua; Shao, Yan; Shi, Bing

    2015-01-01

    The purpose of this study is to ascertain objective nasal measurements from the basal view that are predictive of nasal esthetics in individuals with secondary cleft nasal deformity. Thirty-three patients who had undergone unilateral cleft lip repair were retrospectively reviewed in this study. The degree of nasal deformity was subjectively ranked by seven surgeons using standardized basal-view measurements. Nine physical objective parameters including angles and ratios were measured. Correlations and regressions between these objective and subjective measurements were then analyzed. There was high concordance in subjective measurements by different surgeons (Kendall's harmonious coefficient = W = .825, P = .006). The strongest predictive factors for nasal aesthetics were the ratio of length of nasal alar (r = .370, P = .034) and the degree of deviation of the columnar axis (r = .451, P = .008). The columellar angle had a more powerful effect in rating nasal esthetics. There was reliable concordance in subjective ranking of nasal esthetics by surgeons. Measurement of the columnar angle may serve as an independent, objective predictor of esthetics of the nose.

  7. The role of vaccines in the control of STDs: HPV vaccines.

    PubMed Central

    Frazer, I H

    1996-01-01

    Prophylactic vaccines for genital human papillomavirus (HPV) infection have been shown to be feasible in animal models, and suitable vaccine material based on virus-like particles can be produced in bulk at reasonable cost. Initiation of phase III clinical trials will follow definition of trial outcome measures through further epidemiological studies, and development of assays of host protective immunity. Vaccines could in principle eliminate HPV-related disease, as the human race is the only natural host for the relevant papillomaviruses (PVs). Therapeutic vaccines for genital HPV infection are also possible, but have not yet been demonstrated as feasible in practice because the choice of vaccine antigens is difficult, the method of their optimal delivery is uncertain, and the nature of the relevant antiviral immunity is unknown. PV species specificity will require trials to be conducted in man, which will slow definition of an ideal vaccine. PMID:9038634

  8. Novel vaccines against influenza viruses

    PubMed Central

    Kang, Sang-Moo; Song, Jae-Min; Compans, Richard W.

    2011-01-01

    Killed and live attenuated influenza virus vaccines are effective in preventing and curbing the spread of influenza epidemics when the strains present in the vaccines are closely matched with the predicted epidemic strains. These vaccines are primarily targeted to induce immunity to the variable major target antigen, hemagglutinin (HA) of influenza virus. However, current vaccines are not effective in preventing the emergence of new pandemic or highly virulent viruses. New approaches are being investigated to develop universal influenza virus vaccines as well as to apply more effective vaccine delivery methods. Conserved vaccine targets including the influenza M2 ion channel protein and HA stalk domains are being developed using recombinant technologies to improve the level of cross protection. In addition, recent studies provide evidence that vaccine supplements can provide avenues to further improve current vaccination. PMID:21968298

  9. Comparison between a Single-Channel Nasal Airflow Device and Oximetry for the Diagnosis of Obstructive Sleep Apnea

    PubMed Central

    Rofail, Lydia Makarie; Wong, Keith K.H.; Unger, Gunnar; Marks, Guy B.; Grunstein, Ronald R.

    2010-01-01

    Rationale: The most common single channel devices used for obstructive sleep apnea (OSA) screening are nasal airflow and oximetry. No studies have directly compared their role in diagnosing OSA at home. Study Objectives: To prospectively compare the diagnostic utility of home-based nasal airflow and oximetry to attended polysomnography (PSG) and to assess the diagnostic value of adding oximetry to nasal airflow for OSA. Design: Cross-sectional study Setting: Laboratory and home Participants: Sleep clinic patients with suspected OSA. Interventions: All patients had laboratory PSG and 2 sets of 3 consecutive nights on each device; nasal airflow (Flow Wizard, DiagnoseIT, Australia) and oximetry (Radical Set, Masimo, USA) at home in random order. Results: Ninety-eight of the 105 patients enrolled completed home monitoring. The accuracy of nasal airflow respiratory disturbance index (NF RDI) was not different from oximetry (ODI 3%) for diagnosing OSA (area under the ROC curve (AUC) difference, 0.04; 95% CI of difference −0.05 to 0.12; P = 0.43) over 3 nights of at-home recording. The accuracy of NF RDI was higher after 3 nights compared to one night (AUC difference, 0.05; 95% CI of difference, 0.01 to 0.08; P = 0.04). Addition of oximetry to nasal airflow did not increase the accuracy for predicting OSA compared to nasal airflow alone (P > 0.1). Conclusions: Nasal flow and oximetry have equivalent accuracy for diagnosing OSA in the home setting. Choice of device for home screening of sleep apnea may depend on logistical and service delivery issues. Citation: Makarie Rofail L; Wong KKH; Unger G; Marks GB; Grunstein RR. Comparison between a single-channel nasal airflow device and oximetry for the diagnosis of obstructive sleep apnea. SLEEP 2010;33(8):1106-1114. PMID:20815194

  10. Micro-scale Devices for Transdermal Drug Delivery

    PubMed Central

    Arora, Anubhav; Prausnitz, Mark; Mitragotri, Samir

    2009-01-01

    Skin makes an excellent site for drug and vaccine delivery due to easy accessibility, immuno-surveillance functions, avoidance of macromolecular degradation in the gastrointestinal tract and possibility of self-administration. However, macromolecular drug delivery across the skin is primarily accomplished using hypodermic needles, which have several disadvantages including accidental needle-sticks, pain and needle phobia. These limitations have led to extensive research and development of alternative methods for drug and vaccine delivery across the skin. This review focuses on the recent trends and developments in this field of micro-scale devices for transdermal macromolecular delivery. These include liquid jet injectors, powder injectors, microneedles and thermal microablation. The historical perspective, mechanisms of action, important design parameters, applications and challenges are discussed for each method. PMID:18805472

  11. Liposomal adjuvant development for leishmaniasis vaccines.

    PubMed

    Askarizadeh, Anis; Jaafari, Mahmoud Reza; Khamesipour, Ali; Badiee, Ali

    2017-08-01

    Leishmaniasis is a parasitic disease that ranges in severity from skin lesions to fatality. Since long-lasting protection is induced upon recovery from cutaneous leishmaniasis, development of an effective vaccine is promising. However, there is no vaccine for use in humans yet. It seems limited efficacy in leishmaniasis vaccines is due to lack of an appropriate adjuvant or delivery system. Hence, the use of particulate adjuvants such as liposomes for effective delivery to the antigen presenting cells (APCs) is a valuable strategy to enhance leishmaniasis vaccine efficacy. The extraordinary versatility of liposomes because of their unique amphiphilic and biphasic nature allows for using antigens or immunostimulators within the core, on the surface or within the bilayer, and modulates both the magnitude and the T-helper bias of the immune response. In this review article, we attempt to summarize the role of liposomal adjuvants in the development of Leishmania vaccines and describe the main physicochemical properties of liposomes like phospholipid composition, surface charge, and particle size during formulation design. We also suggest potentially useful formulation strategies in order for future experiments to have a chance to succeed as liposomal vaccines against leishmaniasis.

  12. Liposomal adjuvant development for leishmaniasis vaccines

    PubMed Central

    Askarizadeh, Anis; Jaafari, Mahmoud Reza; Khamesipour, Ali; Badiee, Ali

    2017-01-01

    Leishmaniasis is a parasitic disease that ranges in severity from skin lesions to fatality. Since long-lasting protection is induced upon recovery from cutaneous leishmaniasis, development of an effective vaccine is promising. However, there is no vaccine for use in humans yet. It seems limited efficacy in leishmaniasis vaccines is due to lack of an appropriate adjuvant or delivery system. Hence, the use of particulate adjuvants such as liposomes for effective delivery to the antigen presenting cells (APCs) is a valuable strategy to enhance leishmaniasis vaccine efficacy. The extraordinary versatility of liposomes because of their unique amphiphilic and biphasic nature allows for using antigens or immunostimulators within the core, on the surface or within the bilayer, and modulates both the magnitude and the T-helper bias of the immune response. In this review article, we attempt to summarize the role of liposomal adjuvants in the development of Leishmania vaccines and describe the main physicochemical properties of liposomes like phospholipid composition, surface charge, and particle size during formulation design. We also suggest potentially useful formulation strategies in order for future experiments to have a chance to succeed as liposomal vaccines against leishmaniasis. PMID:29201374

  13. Intranasal Hydrocodone-Acetaminophen Abuse Induced Necrosis of the Nasal Cavity and Pharynx

    PubMed Central

    Alexander, David; Alexander, Keith; Valentino, Joseph

    2012-01-01

    Objectives Two million new users will abuse prescription narcotics this year, most commonly hydrocodone. The most commonly prescribed form is hydrocodone-acetaminophen (HA). Many individuals crush the tablets and snort the product to take advantage of the rapid trans mucosal delivery of narcotics. The resultant pathology of intranasal hydrocodone acetaminophen abuse (INHAA) has been described only in a few case studies. Study Design Retrospective chart review. Methods Two private and one academic otolaryngology practices in Kentucky searched their patient charts for patients with morbidity from intranasal abuse of hydrocodone acetaminophen tablets. We identified thirty-five patients who presented for treatment between 2004 and 2011. Results The majority of patients will initially deny the behavior frequently delaying diagnosis. Physical exam findings of white powder covering an underlying nasal mucosal necrosis are characteristic of this condition during active INHAA. Follow up was limited as only 26% returned for follow up care. Patients commonly presented with orofacial-nasal pain (43%) and sino-nasal congestion and discharge (43%). Active necrosis or prior tissue loss was noted in 77% of patients. Fifty-one percent of patients presented with septal perforations, and 26% with palatal perforations. Two cases of invasive fungal sinusitis were clearly documented with one resulting in death. Conclusions The vast majority of cases presented with characteristic physical findings that included acute necrosis of soft tissue that can progress to destroy oronasal structures. In the absence of invasive fungal disease, the condition is self-limited after cessation of INHAA and performance of local nasal debridement and nasal hygiene. Study Design Chart review, level of evidence: 4 PMID:22965281

  14. Nasal mucosal gene expression in patients with allergic rhinitis with and without nasal polyps.

    PubMed

    Fritz, Stephen B; Terrell, Jeffrey E; Conner, Edward R; Kukowska-Latallo, Jolanta F; Baker, James R

    2003-12-01

    Nasal polyps are a common problem that is difficult to diagnose and treat, in part because the cause of nasal polyposis is unknown. Although information on the pathogenesis of polyposis is lacking, there are reports suggesting that a genetic predisposition underlies this disorder. We sought to better understand the basis of nasal polyposis associated with allergic rhinitis. We hypothesize that the expression of unique genes is associated with the nasal polyposis phenotype. We examined 12000 human genes transcribed in the nasal mucosa of patients with allergic rhinitis with and without nasal polyps. Biopsy specimens of the mucosa of patients with and without polyps were obtained after the patients refrained from the use of topical or systemic steroid therapy for 2 weeks. Thirty-four genes were differentially expressed between the patient groups, including those for inflammatory molecules and putative growth factors. The greatest differential expression identified by the array analysis was for a group of genes associated with neoplasia, including mammaglobin, a gene transcribed 12-fold higher in patients with polyps compared with control patients with rhinitis alone. Quantitative RT-PCR confirmed this differential expression and documented that the number of mammaglobin mRNA copies is actually 64-fold greater in tissues of patients with polyps versus control patients. The specificity of mammaglobin protein expression was evaluated by means of immunohistochemistry, which showed specific staining in nasal polyp mucosal goblet cells only in patients with polyps. These data suggest that nasal polyposis involves deregulated cell growth, using gene activation in some ways similar to a neoplasm. In addition, mammaglobin, a gene of unknown function associated with breast neoplasia, might be related to polyp growth.

  15. Current state and challenges in developing oral vaccines.

    PubMed

    Vela Ramirez, Julia E; Sharpe, Lindsey A; Peppas, Nicholas A

    2017-05-15

    While vaccination remains the most cost effective strategy for disease prevention, communicable diseases persist as the second leading cause of death worldwide. There is a need to design safe, novel vaccine delivery methods to protect against unaddressed and emerging diseases. Development of vaccines administered orally is preferable to traditional injection-based formulations for numerous reasons including improved safety and compliance, and easier manufacturing and administration. Additionally, the oral route enables stimulation of humoral and cellular immune responses at both systemic and mucosal sites to establish broader and long-lasting protection. However, oral delivery is challenging, requiring formulations to overcome the harsh gastrointestinal (GI) environment and avoid tolerance induction to achieve effective protection. Here we address the rationale for oral vaccines, including key biological and physicochemical considerations for next-generation oral vaccine design. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Adenovirus 2, Bordetella bronchiseptica, and Parainfluenza Molecular Diagnostic Assay Results in Puppies After vaccination with Modified Live Vaccines.

    PubMed

    Ruch-Gallie, R; Moroff, S; Lappin, M R

    2016-01-01

    Canine adenovirus 2, parainfluenza, and Bordetella bronchiseptica cause respiratory disease in dogs, and each has a modified live intranasal vaccine available. Molecular diagnostic assays to amplify specific nucleic acids are available for each of these agents. If positive molecular diagnostic assay results are common after vaccination, the positive predictive value of the diagnostic assays for disease would be decreased. To determine the impact of administration of commercially available modified live topical adenovirus 2, B. bronchiseptica, and parainfluenza vaccine has on the results of a commercially available PCR panel. Eight puppies from a research breeding facility negative for these pathogens. Blinded prospective pilot study. Puppies were vaccinated with a single dose of modified live topical adenovirus 2, B. bronchiseptica, and parainfluenza and parenteral dose of adenovirus 2, canine distemper virus, and parvovirus. Nasal and pharyngeal swabs were collected on multiple days and submitted for PCR assay. Nucleic acids of all 3 organisms contained in the topical vaccine were detected from both samples multiple times through 28 days after vaccination with higher numbers of positive samples detected between days 3 and 10 after vaccination. Vaccine status should be considered when interpreting respiratory agent PCR results if modified live vaccines have been used. Development of quantitative PCR and wild-type sequencing are necessary to improve positive predictive value of these assays by distinguishing vaccinate from natural infection. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  17. Development of plant-based mucosal vaccines against widespread infectious diseases.

    PubMed

    Salyaev, Rurick K; Rigano, Maria Manuela; Rekoslavskaya, Natalya I

    2010-08-01

    Mucosal vaccination is a perspective for the control of infectious diseases, since it is capable of inducing humoral and cell-mediated responses. In addition, the delivery of vaccines to mucosal surfaces makes immunization practice safe and acceptable, and eliminates needle-associated risks. Transgenic plants can be used as bioreactors for the production of mucosally delivered protective antigens. This technology shows great promise to simplify and decrease the cost of vaccine delivery. Herein, we review the development of mucosally administered vaccines expressed in transgenic plants. In particular, we evaluate the advantages and disadvantages of using plants for the production of mucosal vaccines against widespread infectious diseases such as HIV, hepatitis B and TB.

  18. Visualization and Quantification of Nasal and Olfactory Deposition in a Sectional Adult Nasal Airway Cast.

    PubMed

    Xi, Jinxiang; Yuan, Jiayao Eddie; Zhang, Yu; Nevorski, Dannielle; Wang, Zhaoxuan; Zhou, Yue

    2016-06-01

    To compare drug deposition in the nose and olfactory region with different nasal devices and administration techniques. A Sar-Gel based colorimetry method will be developed to quantify local deposition rates. A sectional nasal airway cast was developed based on an MRI-based nasal airway model to visualize deposition patterns and measure regional dosages. Four nasal spray pumps and four nebulizers were tested with both standard and point-release administration techniques. Delivered dosages were measured using a high-precision scale. The colorimetry correlation for deposited mass was developed via image processing in Matlab and its performance was evaluated through comparison to experimental measurements. Results show that the majority of nasal spray droplets deposited in the anterior nose while only a small fraction (less than 4.6%) reached the olfactory region. For all nebulizers considered, more droplets went beyond the nasal valve, leading to distinct deposition patterns as a function of both the nebulizer type (droplet size and initial speed) and inhalation flow rate. With the point-release administration, up to 9.0% (±1.9%) of administered drugs were delivered to the olfactory region and 15.7 (±2.4%) to the upper nose using Pari Sinus. Standard nasal devices are inadequate to deliver clinically significant olfactory dosages without excess drug losses in other nasal epitheliums. The Sar-Gel based colorimetry method appears to provide a simple and practical approach to visualize and quantify regional deposition.

  19. Health risks associated with inhaled nasal toxicants.

    PubMed

    Feron, V J; Arts, J H; Kuper, C F; Slootweg, P J; Woutersen, R A

    2001-05-01

    Health risks of inhaled nasal toxicants were reviewed with emphasis on chemically induced nasal lesions in humans, sensory irritation, olfactory and trigeminal nerve toxicity, nasal immunopathology and carcinogenesis, nasal responses to chemical mixtures, in vitro models, and nasal dosimetry- and metabolism-based extrapolation of nasal data in animals to humans. Conspicuous findings in humans are the effects of outdoor air pollution on the nasal mucosa, and tobacco smoking as a risk factor for sinonasal squamous cell carcinoma. Objective methods in humans to discriminate between sensory irritation and olfactory stimulation and between adaptation and habituation have been introduced successfully, providing more relevant information than sensory irritation studies in animals. Against the background of chemoperception as a dominant window of the brain on the outside world, nasal neurotoxicology is rapidly developing, focusing on olfactory and trigeminal nerve toxicity. Better insight in the processes underlying neurogenic inflammation may increase our knowledge of the causes of the various chemical sensitivity syndromes. Nasal immunotoxicology is extremely complex, which is mainly due to the pivotal role of nasal lymphoid tissue in the defense of the middle ear, eye, and oral cavity against antigenic substances, and the important function of the nasal passages in brain drainage in rats. The crucial role of tissue damage and reactive epithelial hyperproliferation in nasal carcinogenesis has become overwhelmingly clear as demonstrated by the recently developed biologically based model for predicting formaldehyde nasal cancer risk in humans. The evidence of carcinogenicity of inhaled complex mixtures in experimental animals is very limited, while there is ample evidence that occupational exposure to mixtures such as wood, leather, or textile dust or chromium- and nickel-containing materials is associated with increased risk of nasal cancer. It is remarkable that these

  20. Engineering intranasal mRNA vaccines to enhance lymph node trafficking and immune responses.

    PubMed

    Li, Man; Li, You; Peng, Ke; Wang, Ying; Gong, Tao; Zhang, Zhirong; He, Qin; Sun, Xun

    2017-12-01

    Intranasal mRNA vaccination provides immediate immune protection against pandemic diseases. Recent studies have shown that diverse forms of polyethyleneimine (PEI) have potent mucosal adjuvant activity, which could significantly facilitate the delivery of intranasal mRNA vaccines. Nevertheless, optimizing the chemical structure of PEI to maximize its adjuvanticity and decrease its toxicity remains a challenge. Here we show that the chemical structure of PEI strongly influences how well nanocomplexes of PEI and mRNA migrate to the lymph nodes and elicit immune responses. Conjugating cyclodextrin (CD) with PEI600 or PEI2k yielded CP (CD-PEI) polymers with different CD/PEI ratios. We analyzed the delivery efficacy of CP600, CP2k, and PEI25k as intranasal mRNA vaccine carriers by evaluating the lymph nodes migration and immune responses. Among these polymers, CP2k/mRNA showed significantly higher in vitro transfection efficiency, stronger abilities to migrate to lymph nodes and stimulate dendritic cells maturation in vivo, which further led to potent humoral and cellular immune responses, and showed lower local and systemic toxicity than PEI25k/mRNA. These results demonstrate the potential of CD-PEI2k/mRNA nanocomplex as a self-adjuvanting vaccine delivery vehicle that traffics to lymph nodes with high efficiency. As we face outbreaks of pandemic diseases such as Zika virus, intranasal mRNA vaccination provides instant massive protection against highly variant viruses. Various polymer-based delivery systems have been successfully applied in intranasal vaccine delivery. However, the influence of molecular structure of the polymeric carriers on the lymph node trafficking and dendritic cell maturation is seldom studied for intranasal vaccination. Therefore, engineering polymer-based vaccine delivery system and elucidating the relationship between molecular structure and the intranasal delivery efficiency are essential for maximizing the immune responses. We hereby

  1. Nasal packing and stenting

    PubMed Central

    Weber, Rainer K.

    2011-01-01

    Nasal packs are indispensable in ENT practice. This study reviews current indications, effectiveness and risks of nasal packs and stents. In endoscopic surgery, nasal packs should always have smooth surfaces to minimize mucosal damage, improve wound healing and increase patient comfort. Functional endoscopic endonasal sinus surgery allows the use of modern nasal packs, since pressure is no longer required. So called hemostatic/resorbable materials are a first step in this direction. However, they may lead to adhesions and foreign body reactions in mucosal membranes. Simple occlusion is an effective method for creating a moist milieu for improved wound healing and avoiding dryness. Stenting of the frontal sinus is recommended if surgery fails to produce a wide, physiologically shaped drainage path that is sufficiently covered by intact tissue. PMID:22073095

  2. An update on the use of laser technology in skin vaccination

    PubMed Central

    Chen, Xinyuan; Wang, Ji; Shah, Dilip; Wu, Mei X

    2014-01-01

    Vaccination via skin often induces stronger immune responses than via muscle. This, in line with potential needle-free, painless delivery, makes skin a very attractive site for immunization. Yet, despite decades of effort, effective skin delivery is still in its infant stage and safe and potent adjuvants for skin vaccination remain largely undefined. We have shown that laser technologies including both fractional and non-fractional lasers can greatly augment vaccine-induced immune response without incurring any significant local and systemic side effects. Laser illumination at specific settings can accelerate the motility of antigen-presenting cells or trigger release of ‘danger’ signals stimulating the immune system. Moreover, several other groups including the authors explore laser technologies for needle-free transcutaneous vaccine delivery. As these laser-mediated resurfacing technologies are convenient, safe and cost-effective, their new applications in vaccination warrant clinical studies in the very near future. PMID:24127871

  3. Appraisal of transverse nasal groove: a study.

    PubMed

    Sathyanarayana, Belagola D; Basavaraj, Halevoor B; Nischal, Kuchangi C; Swaroop, Mukunda R; Umashankar, Puttagangu N; Agrawal, Dhruv P; Swamy, Suchetha S; Okram, Sarda

    2012-01-01

    Transverse nasal groove is a condition of cosmetic concern which awaits due recognition and has been widely described as a shallow groove that extends transversely over the dorsum of nose. However, we observed variations in the clinical presentations of this entity, hitherto undescribed in literature. We conducted a clinicoepidemiological study of transverse nasal lesions in patients attending our outpatient department. We conducted a prospective observational study. We screened all patients attending our out-patient department for presence of transverse nasal lesions, signs of any dermatosis and associated other skin conditions. One hundred patients were recruited in the study. Females (80%) predominated over males. Most patients were of 15-45 years age group (70%). Majority of the transverse nasal lesions were classical transverse nasal groove (39%) and others included transverse nasal line (28%), strip (28%), ridge (4%) and loop (1%). Seborrhoeic diathesis was the most common condition associated with transverse nasal lesion. Occurrence of transverse nasal line, strip, ridge and loop, in addition to classical transverse nasal groove implies that latter is actually a subset of transverse nasal lesions. Common association of this entity with seborrheic dermatitis, seborrhea and dandruff raises a possibility of whether transverse nasal lesion is a manifestation of seborrheic diathesis.

  4. mRNA Cancer Vaccines-Messages that Prevail.

    PubMed

    Grunwitz, Christian; Kranz, Lena M

    2017-01-01

    During the last decade, mRNA became increasingly recognized as a versatile tool for the development of new innovative therapeutics. Especially for vaccine development, mRNA is of outstanding interest and numerous clinical trials have been initiated. Strikingly, all of these studies have proven that large-scale GMP production of mRNA is feasible and concordantly report a favorable safety profile of mRNA vaccines. Induction of T-cell immunity is a multi-faceted process comprising antigen acquisition, antigen processing and presentation, as well as immune stimulation. The effectiveness of mRNA vaccines is critically dependent on making the antigen(s) of interest available to professional antigen-presenting cells, especially DCs. Efficient delivery of mRNA into DCs in vivo remains a major challenge in the mRNA vaccine field. This review summarizes the principles of mRNA vaccines and highlights the importance of in vivo mRNA delivery and recent advances in harnessing their therapeutic potential.

  5. Oral Modeling of an Adenovirus-Based Quadrivalent Influenza Vaccine in Ferrets and Mice.

    PubMed

    Scallan, Ciaran D; Lindbloom, Jonathan D; Tucker, Sean N

    2016-06-01

    Oral vaccines delivered as tablets offer a number of advantages over traditional parenteral-based vaccines including the ease of delivery, lack of needles, no need for trained medical personnel, and the ability to formulate into temperature-stable tablets. We have been evaluating an oral vaccine platform based on recombinant adenoviral vectors for the purpose of creating a prophylactic vaccine to prevent influenza, and have demonstrated vaccine efficacy in animal models and substantial immunogenicity in humans. These studies have evaluated monovalent vaccines to date. To protect against the major circulating A and B influenza strains, a multivalent influenza vaccine will be required. In this study, the immunogenicity of orally delivered monovalent, bivalent, trivalent, and quadrivalent vaccines was tested in ferrets and mice. The various vaccine combinations were tested by blending monovalent recombinant adenovirus vaccines, each expressing hemagglutinin from a single strain. Human tablet delivery was modeled in animals by oral gavage in mice and by endoscopic delivery in ferrets. We demonstrated minimal interference between the various vaccine vectors when used in combination and that the oral quadrivalent vaccine compared favorably to an approved trivalent inactivated vaccine. The quadrivalent vaccine presented here produced immune responses that we predict should be capable of providing protection against multiple influenza strains, and the platform should have applications to other multivalent vaccines. Vaxart, Inc.

  6. Nasal budesonide offers superior symptom relief in perennial allergic rhinitis in comparison to nasal azelastine.

    PubMed

    Stern, M A; Wade, A G; Ridout, S M; Cambell, L M

    1998-10-01

    Allergic rhinitis is usually treated with oral antihistamines or nasal steroids. Topically active nasal antihistamine is a new treatment modality for allergic rhinitis. The efficacy in comparison to well established topical treatment alternatives is not fully known. To compare the efficacy of intranasally administered azelastine to budesonide, at their respectively recommended dosage, on the symptoms of perennial rhinitis patients. A placebo-controlled, randomized, parallel group study was conducted to compare the efficacy and tolerability of intranasal budesonide aqueous suspension (256 microg once daily) with azelastine hydrochloride nasal spray (280 microg twice daily (560 microg/day)) and with placebo in the treatment of perennial allergic rhinitis. The 195 patients (with at least a 2-year history of perennial allergic rhinitis) recorded individual nasal symptom scores, the degree of symptom control achieved and any adverse events experienced over a 2-week baseline period and a 6-week treatment period. Following treatment, the reductions in mean combined and individual nasal symptom scores from baseline values were significantly greater in the budesonide group compared with the placebo group (P < .0001 for all variables except runny nose P = .01). In patients treated with budesonide, there were also significantly larger reductions from baseline values in combined nasal symptom scores (P < .01) and in scores for all individual nasal symptoms (P < or = .05) compared with those treated with azelastine. The reductions from baseline in both combined and individual nasal symptom scores did not differ between azelastine and placebo. The study medications were well tolerated, producing no unexpected or serious treatment-related adverse events. A once-daily dose of 256 microg of intranasal budesonide aqueous suspension is significantly more effective at relieving the symptoms of perennial allergic rhinitis compared with a twice daily dose of 280 microg of azelastine

  7. Virus-Like Particle, Liposome, and Polymeric Particle-Based Vaccines against HIV-1

    PubMed Central

    Gao, Yong; Wijewardhana, Chanuka; Mann, Jamie F. S.

    2018-01-01

    It is acknowledged that vaccines remain the best hope for eliminating the HIV-1 epidemic. However, the failure to produce effective vaccine immunogens and the inability of conventional delivery strategies to elicit the desired immune responses remains a central theme and has ultimately led to a significant roadblock in HIV vaccine development. Consequently, significant efforts have been applied to generate novel vaccine antigens and delivery agents, which mimic viral structures for optimal immune induction. Here, we review the latest developments that have occurred in the nanoparticle vaccine field, with special emphasis on strategies that are being utilized to attain highly immunogenic, systemic, and mucosal anti-HIV humoral and cellular immune responses. This includes the design of novel immunogens, the central role of antigen-presenting cells, delivery routes, and biodistribution of nanoparticles to lymph nodes. In particular, we will focus on virus-like-particle formulations and their preclinical uses within the HIV prophylactic vaccine setting. PMID:29541072

  8. Recent advances in recombinant protein-based malaria vaccines

    PubMed Central

    Draper, Simon J.; Angov, Evelina; Horii, Toshihiro; Miller, Louis H.; Srinivasan, Prakash; Theisen, Michael; Biswas, Sumi

    2015-01-01

    Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a key priority. It is widely established that multiple stages of the parasite's complex lifecycle within the human host and mosquito vector are susceptible to vaccine-induced antibodies. The mainstay approach to antibody induction by subunit vaccination has been the delivery of protein antigen formulated in adjuvant. Extensive efforts have been made in this endeavor with respect to malaria vaccine development, especially with regard to target antigen discovery, protein expression platforms, adjuvant testing, and development of soluble and virus-like particle (VLP) delivery platforms. The breadth of approaches to protein-based vaccines is continuing to expand as innovative new concepts in next-generation subunit design are explored, with the prospects for the development of a highly effective multi-component/multi-stage/multi-antigen formulation seeming ever more likely. This review will focus on recent progress in protein vaccine design, development and/or clinical testing for a number of leading malaria antigens from the sporozoite-, merozoite- and sexual-stages of the parasite's lifecycle–including PfCelTOS, PfMSP1, PfAMA1, PfRH5, PfSERA5, PfGLURP, PfMSP3, Pfs48/45 and Pfs25. Future prospects and challenges for the development, production, human delivery and assessment of protein-based malaria vaccines are discussed. PMID:26458807

  9. Recent advances in recombinant protein-based malaria vaccines.

    PubMed

    Draper, Simon J; Angov, Evelina; Horii, Toshihiro; Miller, Louis H; Srinivasan, Prakash; Theisen, Michael; Biswas, Sumi

    2015-12-22

    Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a key priority. It is widely established that multiple stages of the parasite's complex lifecycle within the human host and mosquito vector are susceptible to vaccine-induced antibodies. The mainstay approach to antibody induction by subunit vaccination has been the delivery of protein antigen formulated in adjuvant. Extensive efforts have been made in this endeavor with respect to malaria vaccine development, especially with regard to target antigen discovery, protein expression platforms, adjuvant testing, and development of soluble and virus-like particle (VLP) delivery platforms. The breadth of approaches to protein-based vaccines is continuing to expand as innovative new concepts in next-generation subunit design are explored, with the prospects for the development of a highly effective multi-component/multi-stage/multi-antigen formulation seeming ever more likely. This review will focus on recent progress in protein vaccine design, development and/or clinical testing for a number of leading malaria antigens from the sporozoite-, merozoite- and sexual-stages of the parasite's lifecycle-including PfCelTOS, PfMSP1, PfAMA1, PfRH5, PfSERA5, PfGLURP, PfMSP3, Pfs48/45 and Pfs25. Future prospects and challenges for the development, production, human delivery and assessment of protein-based malaria vaccines are discussed. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Childhood vaccination in informal urban settlements in Nairobi, Kenya: who gets vaccinated?

    PubMed

    Mutua, Martin K; Kimani-Murage, Elizabeth; Ettarh, Remare R

    2011-01-04

    the birth dose of OPV, respectively. Full vaccination coverage (57.5%) was higher than up-to-date coverage (51.8%) at 12 months overall, and in both slum settlements, using data from cards. Multivariate analysis showed that household assets and expenditure, ethnicity, place of delivery, mother's level of education, age and parity were all predictors of full vaccination among children living in the slums. The findings show the extent to which children resident in slums are underserved with vaccination and indicate that service delivery of immunization services in the urban slums needs to be reassessed to ensure that all children are reached.

  11. Childhood vaccination in informal urban settlements in Nairobi, Kenya: Who gets vaccinated?

    PubMed Central

    2011-01-01

    .3% and 51.8% with and without the birth dose of OPV, respectively. Full vaccination coverage (57.5%) was higher than up-to-date coverage (51.8%) at 12 months overall, and in both slum settlements, using data from cards. Multivariate analysis showed that household assets and expenditure, ethnicity, place of delivery, mother's level of education, age and parity were all predictors of full vaccination among children living in the slums. Conclusions The findings show the extent to which children resident in slums are underserved with vaccination and indicate that service delivery of immunization services in the urban slums needs to be reassessed to ensure that all children are reached. PMID:21205306

  12. Costs of delivering human papillomavirus vaccination to schoolgirls in Mwanza Region, Tanzania

    PubMed Central

    2012-01-01

    Background Cervical cancer is the leading cause of female cancer-related deaths in Tanzania. Vaccination against human papillomavirus (HPV) offers a new opportunity to control this disease. This study aimed to estimate the costs of a school-based HPV vaccination project in three districts in Mwanza Region (NCT ID: NCT01173900), Tanzania and to model incremental scaled-up costs of a regional vaccination program. Methods We first conducted a top-down cost analysis of the vaccination project, comparing observed costs of age-based (girls born in 1998) and class-based (class 6) vaccine delivery in a total of 134 primary schools. Based on the observed project costs, we then modeled incremental costs of a scaled-up vaccination program for Mwanza Region from the perspective of the Tanzanian government, assuming that HPV vaccines would be delivered through the Expanded Programme on Immunization (EPI). Results Total economic project costs for delivering 3 doses of HPV vaccine to 4,211 girls were estimated at about US$349,400 (including a vaccine price of US$5 per dose). Costs per fully-immunized girl were lower for class-based delivery than for age-based delivery. Incremental economic scaled-up costs for class-based vaccination of 50,290 girls in Mwanza Region were estimated at US$1.3 million. Economic scaled-up costs per fully-immunized girl were US$26.41, including HPV vaccine at US$5 per dose. Excluding vaccine costs, vaccine could be delivered at an incremental economic cost of US$3.09 per dose and US$9.76 per fully-immunized girl. Financial scaled-up costs, excluding costs of the vaccine and salaries of existing staff were estimated at US$1.73 per dose. Conclusions Project costs of class-based vaccination were found to be below those of age-based vaccination because of more eligible girls being identified and higher vaccine uptake. We estimate that vaccine can be delivered at costs that would make HPV vaccination a very cost-effective intervention. Potentially

  13. Costs of delivering human papillomavirus vaccination to schoolgirls in Mwanza Region, Tanzania.

    PubMed

    Quentin, Wilm; Terris-Prestholt, Fern; Changalucha, John; Soteli, Selephina; Edmunds, W John; Hutubessy, Raymond; Ross, David A; Kapiga, Saidi; Hayes, Richard; Watson-Jones, Deborah

    2012-11-13

    Cervical cancer is the leading cause of female cancer-related deaths in Tanzania. Vaccination against human papillomavirus (HPV) offers a new opportunity to control this disease. This study aimed to estimate the costs of a school-based HPV vaccination project in three districts in Mwanza Region (NCT ID: NCT01173900), Tanzania and to model incremental scaled-up costs of a regional vaccination program. We first conducted a top-down cost analysis of the vaccination project, comparing observed costs of age-based (girls born in 1998) and class-based (class 6) vaccine delivery in a total of 134 primary schools. Based on the observed project costs, we then modeled incremental costs of a scaled-up vaccination program for Mwanza Region from the perspective of the Tanzanian government, assuming that HPV vaccines would be delivered through the Expanded Programme on Immunization (EPI). Total economic project costs for delivering 3 doses of HPV vaccine to 4,211 girls were estimated at about US$349,400 (including a vaccine price of US$5 per dose). Costs per fully-immunized girl were lower for class-based delivery than for age-based delivery. Incremental economic scaled-up costs for class-based vaccination of 50,290 girls in Mwanza Region were estimated at US$1.3 million. Economic scaled-up costs per fully-immunized girl were US$26.41, including HPV vaccine at US$5 per dose. Excluding vaccine costs, vaccine could be delivered at an incremental economic cost of US$3.09 per dose and US$9.76 per fully-immunized girl. Financial scaled-up costs, excluding costs of the vaccine and salaries of existing staff were estimated at US$1.73 per dose. Project costs of class-based vaccination were found to be below those of age-based vaccination because of more eligible girls being identified and higher vaccine uptake. We estimate that vaccine can be delivered at costs that would make HPV vaccination a very cost-effective intervention. Potentially, integrating HPV vaccine delivery with cost

  14. Nasal symptoms following endoscopic transsphenoidal pituitary surgery: assessment using the General Nasal Patient Inventory.

    PubMed

    Wang, Yi Yuen; Srirathan, Vinothan; Tirr, Erica; Kearney, Tara; Gnanalingham, Kanna K

    2011-04-01

    The endoscopic approach for pituitary tumors is a recent innovation and is said to reduce the nasal trauma associated with transnasal transsphenoidal surgery. The authors assessed the temporal changes in the rhinological symptoms following endoscopic transsphenoidal surgery for pituitary lesions, using the General Nasal Patient Inventory (GNPI). The GNPI was administered to 88 consecutive patients undergoing endoscopic transsphenoidal surgery at 3 time points (presurgery, 3-6 months postsurgery, and at final follow-up). The total GNPI score and the scores for the individual GNPI questions were calculated and differences between groups were assessed once before surgery, several months after surgery, and at final follow-up. Of a maximum possible score of 135, the mean GNPI score at 3-6 months postsurgery was only 12.9 ± 12 and was not significantly different from the preoperative score (10.4 ± 13) or final follow-up score (10.3 ± 10). Patients with functioning tumors had higher GNPI scores than those with nonfunctioning tumors for each of these time points (p < 0.05). Individually, a mild increase in symptom severity was seen for symptoms attributable to the nasal trauma of surgery, with partial recovery (nasal sores and bleeding) or complete recovery (nasal blockage, painful sinuses, and unpleasant nasal smell) by final follow-up (p < 0.05). Progressive improvements in symptom severity were seen for symptoms more attributable to tumor mass preoperatively (for example, headaches and painkiller use [p < 0.05]). In total, by final follow-up 8 patients (9%) required further treatment or advice for ongoing nasal symptoms. Endoscopic transsphenoidal surgery is a well-tolerated minimally invasive procedure for pituitary fossa lesions. Overall patient-assessed nasal symptoms do not change, but some individual symptoms may show a mild worsening or overall improvement.

  15. Development of standard operating procedures to obtain longitudinal vaginal specimens from nulliparous rabbits as part of HIV vaccine mucosal immunogenicity studies.

    PubMed

    Gómez Román, Victor Raúl; Vinner, Lasse; Grevstad, Berit; Hansen, Jesper Juhl; Wegmann, Frank; Spetz, Anna-Lena; Fomsgaard, Anders

    2010-12-15

    The New Zealand white rabbit model (Oryctolagus cuniculus) is widely used to test whether HIV vaccine candidates elicit systemic antibody responses; however, its use in mucosal immunology has not been fully exploited due to the difficulty in collecting mucosal specimens longitudinally and reproducibly. Here we describe feasible and non-feasible methods to collect vaginal and nasal specimens from nulliparous rabbits. Non-feasible methods were those resulting in poor reproducibility and considerable animal twitching during sampling, whereas feasible methods resulted in no animal twitching and potential for sampling reproducibility. Standard operating procedures (SOPs) were implemented to collect vaginal swabs yielding total IgA titres ranging from 12,500 to 312,500. Intranasal immunisation with a naked DNA vaccine encoding HIV gp140 elicited HIV envelope-specific IgA detectable in nasal but not in vaginal secretions. Our methods provide an alternative to reliably assess pre- and post-vaccination mucosal antibody titres longitudinally in rabbits as part of mucosal HIV vaccine immunogenicity studies. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Mannosylated protamine as a novel DNA vaccine carrier for effective induction of anti-tumor immune responses.

    PubMed

    Zeng, Zhaoyan; Dai, Shuang; Jiao, Yan; Jiang, Lei; Zhao, Yuekui; Wang, Bo; Zong, Li

    2016-06-15

    Gene immunotherapy has been developed as a promising strategy for inhibition of tumor growth. In the study, mannosylated protamine sulphate (MPS) was used as a novel DNA vaccine carrier to enhance transfection efficiency and anti-tumor immune responses. Anti-GRP DNA vaccine (pGRP) was selected as a model gene and condensed by MPS to form MPS/pGRP nanoparticles. The cellular uptake and transfection efficiency of MPS/pGRP nanoparticles in macrophages were evaluated. The effect of the nanoparticles in enhancing GRP-specific humoral immune response was then evaluated by nasal vaccination of nanoparticles in mice. The results demonstrated that both the cellular uptake and transfection efficiency of MPS nanoparticles in macrophages were higher than those of protamine nanoparticles. MPS/pGRP nanoparticles stimulated the production of higher titers (3.9×10(3)) of specific antibodies against GRP than those of protamine/pGRP nanoparticles (6.4×10(2), p<0.01) and intramuscular injection pGRP solution (2.5×10(3), p<0.05). Furthermore, the inhibitory rate in MPS/pGRP nanoparticles group (65.80%) was significantly higher than that in protamine/pGRP nanoparticles group (35.13%) and pGRP solution group (43.39%). Hence, it is evident that MPS is an efficient targeting gene delivery carrier which could improve in vitro transfection efficiency as well as anti-tumor immunotherapy in mice. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. An Estimation of Private Household Costs to Receive Free Oral Cholera Vaccine in Odisha, India.

    PubMed

    Mogasale, Vittal; Kar, Shantanu K; Kim, Jong-Hoon; Mogasale, Vijayalaxmi V; Kerketta, Anna S; Patnaik, Bikash; Rath, Shyam Bandhu; Puri, Mahesh K; You, Young Ae; Khuntia, Hemant K; Maskery, Brian; Wierzba, Thomas F; Sah, Binod

    2015-01-01

    Service provider costs for vaccine delivery have been well documented; however, vaccine recipients' costs have drawn less attention. This research explores the private household out-of-pocket and opportunity costs incurred to receive free oral cholera vaccine during a mass vaccination campaign in rural Odisha, India. Following a government-driven oral cholera mass vaccination campaign targeting population over one year of age, a questionnaire-based cross-sectional survey was conducted to estimate private household costs among vaccine recipients. The questionnaire captured travel costs as well as time and wage loss for self and accompanying persons. The productivity loss was estimated using three methods: self-reported, government defined minimum daily wages and gross domestic product per capita in Odisha. On average, families were located 282.7 (SD = 254.5) meters from the nearest vaccination booths. Most family members either walked or bicycled to the vaccination sites and spent on average 26.5 minutes on travel and 15.7 minutes on waiting. Depending upon the methodology, the estimated productivity loss due to potential foregone income ranged from $0.15 to $0.29 per dose of cholera vaccine received. The private household cost of receiving oral cholera vaccine constituted 24.6% to 38.0% of overall vaccine delivery costs. The private household costs resulting from productivity loss for receiving a free oral cholera vaccine is a substantial proportion of overall vaccine delivery cost and may influence vaccine uptake. Policy makers and program managers need to recognize the importance of private costs and consider how to balance programmatic delivery costs with private household costs to receive vaccines.

  18. Novel transgenic rice-based vaccines.

    PubMed

    Azegami, Tatsuhiko; Itoh, Hiroshi; Kiyono, Hiroshi; Yuki, Yoshikazu

    2015-04-01

    Oral vaccination can induce both systemic and mucosal antigen-specific immune responses. To control rampant mucosal infectious diseases, the development of new effective oral vaccines is needed. Plant-based vaccines are new candidates for oral vaccines, and have some advantages over the traditional vaccines in cost, safety, and scalability. Rice seeds are attractive for vaccine production because of their stability and resistance to digestion in the stomach. The efficacy of some rice-based vaccines for infectious, autoimmune, and other diseases has been already demonstrated in animal models. We reported the efficacy in mice, safety, and stability of a rice-based cholera toxin B subunit vaccine called MucoRice-CTB. To advance MucoRice-CTB for use in humans, we also examined its efficacy and safety in primates. The potential of transgenic rice production as a new mucosal vaccine delivery system is reviewed from the perspective of future development of effective oral vaccines.

  19. Adjuncts to Improve Nasal Reconstruction Results.

    PubMed

    Gordon, Shayna Lee; Hurst, Eva A

    2017-02-01

    The final cosmetic appearance of nasal reconstruction scars is of paramount importance to both the patient and surgeon. Ideal postreconstruction nasal scars are flat and indistinguishable from surrounding skin. Unfortunately, even with meticulous surgical execution, nasal scars can occasionally be suboptimal. Abnormal fibroblast response can lead to hypertrophic nasal scars, and excessive angiogenesis may lead to telangiectasias or an erythematous scar. Imperfect surgical closure or poor postoperative management can lead to surgical outcomes with step-offs, depressions, suture marks, or dyspigmentation. Aesthetically unacceptable nasal scars can cause pruritus, tenderness, pain, sleep disturbance, and anxiety and depression in postsurgical patients. Fortunately, there are several minimally invasive or noninvasive techniques that allow for enhancement and improvement of cosmetic results with minimal risk and associated downtime. This article provides an overview of adjuncts to improve nasal reconstruction with a focus on techniques to be used in the postoperative period. Armed with an understanding of relevant available therapies, skillful surgeons may drastically improve the final cosmesis and outcome of nasal reconstruction scars. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  20. Crude childhood vaccination coverage in West Africa: Trends and predictors of completeness.

    PubMed

    Kazungu, Jacob S; Adetifa, Ifedayo M O

    2017-02-15

    Background : Africa has the lowest childhood vaccination coverage worldwide. If the full benefits of childhood vaccination programmes are to be enjoyed in sub-Saharan Africa, all countries need to improve on vaccine delivery to achieve and sustain high coverage. In this paper, we review trends in vaccination coverage, dropouts between vaccine doses and explored the country-specific predictors of complete vaccination in West Africa.  Methods : We utilized datasets from the Demographic and Health Surveys Program, available for Benin, Burkina Faso, The Gambia, Ghana, Guinea, Cote d'Ivoire, Liberia, Mali, Niger, Nigeria, Senegal, Sierra Leone and Togo, to obtain coverage for Bacillus Calmette-Guerin, polio, measles, and diphtheria, pertussis and tetanus (DPT) vaccines in children aged 12 - 23 months. We also calculated the DPT1-to-DPT3 and DPT1-to-measles dropouts, and proportions of the fully immunised child (FIC). Factors predictive of FIC were explored using Chi-squared tests and multivariable logistic regression.  Results : Overall, there was a trend of increasing vaccination coverage. The proportion of FIC varied significantly by country (range 24.1-81.4%, mean 49%). DPT1-to-DPT3 dropout was high (range 5.1% -33.9%, mean 16.3%). Similarly, DPT1-measles dropout exceeded 10% in all but four countries. Although no single risk factor was consistently associated with FIC across these countries, maternal education, delivery in a health facility, possessing a vaccine card and a recent post delivery visit to a health facility were the key predictors of complete vaccination.  Conclusions : The low numbers of fully immunised children and high dropout between vaccine doses highlights weaknesses and the need to strengthen the healthcare and routine immunization delivery systems in this region. Country-specific correlates of complete vaccination should be explored further to identify interventions required to increase vaccination coverage. Despite the promise of an

  1. Presurgical Nasal Molding With a Nasal Spring in Patients With Mild-to-Moderate Nasal Deformity With Incomplete Unilateral Cleft Lip With or Without Cleft Palate.

    PubMed

    Peanchitlertkajorn, Supakit

    2018-01-01

    Traditional nasoalveolar molding (NAM) requires steep learning curve for clinicians and significant compliance from parents. Nasal springs have been developed by the author to simplify presurgical nasal molding. This article presents the design, construction, and application of the spring. The treatment goal is to improve nasal deformity prior to primary repair in infants born with incomplete unilateral cleft lip with or without cleft palate. The design, fabrication, and utility of the nasal spring are described. The spring has a simpler design and construction compared to a traditional NAM appliance. Two patients with incomplete unilateral cleft lip with and without cleft palate are presented. The spring is constructed and delivered. The active arm of the spring can be 3-dimensionally (3-D) adjusted to mold the alar cartilage of the affected nostril. The spring does not require an oral plate for adherence as a traditional NAM appliance does, hence an oral impression is not needed. The spring is easy for clinicians to adjust. It also requires less compliance by parents. Main Outcome Measures/Results: The presurgical molding achieved by the use of a nasal spring improved surgical nasolabial aesthetic outcomes. The nasal springs are effective in reducing the initial cleft nasal deformity. This facilitates primary surgical cleft lip and nose correction and improves surgical outcomes in patients with incomplete unilateral cleft lip with or without cleft palate.

  2. Management of Intractable Nasal Hyperreactivity by Selective Resection of Posterior Nasal Nerve Branches

    PubMed Central

    Takahara, Daisuke; Hamamoto, Takao; Ishino, Takashi; Hirakawa, Katsuhiro

    2017-01-01

    The posterior nasal nerves emerge from the sphenopalatine foramen and contain sensory and autonomic nerve components. Posterior nasal neurectomy is an effective method to remove pathological neural networks surrounding the inferior turbinate that cause unregulated nasal hypersensitivity with excess secretion in patients with severe allergic rhinitis (AR). We describe the sophisticated endoscopic surgical procedure that allows feasible access to the confined area and selective resection of the nerve branches with the preservation of the sphenopalatine artery (SPA). We retrospectively analyzed the cases of 23 symptomatic severe AR patients who failed to respond to standard medical treatment and underwent surgery. There have been no major complications after surgery including nasal bleeding or transient numbness of the upper teeth. The mean total nasal symptom scores (TNSS) were decreased by 70.2% at 12 months after the procedure. Our comparison of the clinical effectiveness based on the number of severed nerve branches revealed that the improvement of the TNSS was significantly higher in patients with >2 branches. We conclude that this minimally invasive technique that preserves the SPA is clinically useful and decreases the rate of postoperative complications. This trial is registered with UMIN000029025. PMID:29379524

  3. Management of Intractable Nasal Hyperreactivity by Selective Resection of Posterior Nasal Nerve Branches.

    PubMed

    Takahara, Daisuke; Takeno, Sachio; Hamamoto, Takao; Ishino, Takashi; Hirakawa, Katsuhiro

    2017-01-01

    The posterior nasal nerves emerge from the sphenopalatine foramen and contain sensory and autonomic nerve components. Posterior nasal neurectomy is an effective method to remove pathological neural networks surrounding the inferior turbinate that cause unregulated nasal hypersensitivity with excess secretion in patients with severe allergic rhinitis (AR). We describe the sophisticated endoscopic surgical procedure that allows feasible access to the confined area and selective resection of the nerve branches with the preservation of the sphenopalatine artery (SPA). We retrospectively analyzed the cases of 23 symptomatic severe AR patients who failed to respond to standard medical treatment and underwent surgery. There have been no major complications after surgery including nasal bleeding or transient numbness of the upper teeth. The mean total nasal symptom scores (TNSS) were decreased by 70.2% at 12 months after the procedure. Our comparison of the clinical effectiveness based on the number of severed nerve branches revealed that the improvement of the TNSS was significantly higher in patients with >2 branches. We conclude that this minimally invasive technique that preserves the SPA is clinically useful and decreases the rate of postoperative complications. This trial is registered with UMIN000029025.

  4. Plant-made vaccine antigens and biopharmaceuticals

    PubMed Central

    Daniell, Henry; Singh, Nameirakpam D.; Mason, Hugh; Streatfield, Stephen J.

    2009-01-01

    Plant cells are ideal bioreactors for the production and oral delivery of vaccines and biopharmaceuticals, eliminating the need for expensive fermentation, purification, cold storage, transportation and sterile delivery. Plant-made vaccines have been developed for two decades but none has advanced beyond Phase I. However, two plant-made biopharmaceuticals are now advancing through Phase II and Phase III human clinical trials. In this review, we evaluate the advantages and disadvantages of different plant expression systems (stable nuclear and chloroplast or transient viral) and their current limitations or challenges. We provide suggestions for advancing this valuable concept for clinical applications and conclude that greater research emphasis is needed on large scale production, purification, functional characterization, oral delivery and preclinical evaluation. PMID:19836291

  5. [Disturbances of nasal aerodynamics in patients with the curved nasal septum and the rationale for its surgical correction].

    PubMed

    Tulebaev, R K; Mustafin, A A; Zholdybaeva, Z T

    2011-01-01

    Serious disturbances of nasal aerodynamics contribute to the development of diseases of the broncho-pulmonary apparatus. The early recognition of ventilation problems in patients with the curved nasal septum is paramount for the efficacious prevention and treatment of respiratory complications. The authors describe principles of rhinosurgical correction of affected nasal aerodynamics in patients with the curved nasal septum.

  6. Vaccine Safety Resources for Nurses

    PubMed Central

    Shimabukuro, Tom T.; Hibbs, Beth F.; Moro, Pedro L.; Broder, Karen R.; Vellozzi, Claudia

    2015-01-01

    Overview Nurses are on the front lines of health care delivery, and many of them routinely administer immunizations. The authors describe the Centers for Disease Control and Prevention’s (CDC) vaccine safety monitoring systems, explaining how nurses can access inquiry channels and other immunization information resources. Examples of recent vaccine safety inquiries are also provided. PMID:26222474

  7. A Nasal Epithelial Receptor for Staphylococcus aureus WTA Governs Adhesion to Epithelial Cells and Modulates Nasal Colonization

    PubMed Central

    Faulstich, Manuela; Grau, Timo; Severin, Yannik; Unger, Clemens; Hoffmann, Wolfgang H.; Rudel, Thomas; Autenrieth, Ingo B.; Weidenmaier, Christopher

    2014-01-01

    Nasal colonization is a major risk factor for S. aureus infections. The mechanisms responsible for colonization are still not well understood and involve several factors on the host and the bacterial side. One key factor is the cell wall teichoic acid (WTA) of S. aureus, which governs direct interactions with nasal epithelial surfaces. We report here the first receptor for the cell wall glycopolymer WTA on nasal epithelial cells. In several assay systems this type F-scavenger receptor, termed SREC-I, bound WTA in a charge dependent manner and mediated adhesion to nasal epithelial cells in vitro. The impact of WTA and SREC-I interaction on epithelial adhesion was especially pronounced under shear stress, which resembles the conditions found in the nasal cavity. Most importantly, we demonstrate here a key role of the WTA-receptor interaction in a cotton rat model of nasal colonization. When we inhibited WTA mediated adhesion with a SREC-I antibody, nasal colonization in the animal model was strongly reduced at the early onset of colonization. More importantly, colonization stayed low over an extended period of 6 days. Therefore we propose targeting of this glycopolymer-receptor interaction as a novel strategy to prevent or control S. aureus nasal colonization. PMID:24788600

  8. Costs of vaccine programs across 94 low- and middle-income countries.

    PubMed

    Portnoy, Allison; Ozawa, Sachiko; Grewal, Simrun; Norman, Bryan A; Rajgopal, Jayant; Gorham, Katrin M; Haidari, Leila A; Brown, Shawn T; Lee, Bruce Y

    2015-05-07

    While new mechanisms such as advance market commitments and co-financing policies of the GAVI Alliance are allowing low- and middle-income countries to gain access to vaccines faster than ever, understanding the full scope of vaccine program costs is essential to ensure adequate resource mobilization. This costing analysis examines the vaccine costs, supply chain costs, and service delivery costs of immunization programs for routine immunization and for supplemental immunization activities (SIAs) for vaccines related to 18 antigens in 94 countries across the decade, 2011-2020. Vaccine costs were calculated using GAVI price forecasts for GAVI-eligible countries, and assumptions from the PAHO Revolving Fund and UNICEF for middle-income countries not supported by the GAVI Alliance. Vaccine introductions and coverage levels were projected primarily based on GAVI's Adjusted Demand Forecast. Supply chain costs including costs of transportation, storage, and labor were estimated by developing a mechanistic model using data generated by the HERMES discrete event simulation models. Service delivery costs were abstracted from comprehensive multi-year plans for the majority of GAVI-eligible countries and regression analysis was conducted to extrapolate costs to additional countries. The analysis shows that the delivery of the full vaccination program across 94 countries would cost a total of $62 billion (95% uncertainty range: $43-$87 billion) over the decade, including $51 billion ($34-$73 billion) for routine immunization and $11 billion ($7-$17 billion) for SIAs. More than half of these costs stem from service delivery at $34 billion ($21-$51 billion)-with an additional $24 billion ($13-$41 billion) in vaccine costs and $4 billion ($3-$5 billion) in supply chain costs. The findings present the global costs to attain the goals envisioned during the Decade of Vaccines to prevent millions of deaths by 2020 through more equitable access to existing vaccines for people in all

  9. Analytical Challenges and Regulatory Requirements for Nasal Drug Products in Europe and the U.S.

    PubMed Central

    Trows, Sabrina; Wuchner, Klaus; Spycher, Rene; Steckel, Hartwig

    2014-01-01

    Nasal drug delivery can be assessed by a variety of means and regulatory agencies, e.g., the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published a set of guidelines and regulations proposing in vitro test methods for the characterization of nasal drug products. This article gives a summary of the FDA and EMA requirements regarding the determination of droplet size distribution (DSD), plume geometry, spray pattern and shot weights of solution nasal sprays and discusses the analytical challenges that can occur when performing these measurements. In order to support findings from the literature, studies were performed using a standard nasal spray pump and aqueous model formulations. The aim was to identify possible method-, device- and formulation-dependent influencing factors. The literature review, as well as the results from the studies show that DSD, plume geometry and spray pattern are influenced by, e.g., the viscosity of the solution, the design of the device and the actuation parameters, particularly the stroke length, actuation velocity and actuation force. The dominant factor influencing shot weights, however, is the adjustment of the actuation parameters, especially stroke length and actuation velocity. Consequently, for routine measurements assuring, e.g., the quality of a solution nasal spray or, for in vitro bioequivalence studies, the critical parameters, have to be identified and considered in method development in order to obtain reproducible and reliable results. PMID:24732068

  10. Enhancing Oral Vaccine Potency by Targeting Intestinal M Cells

    PubMed Central

    Azizi, Ali; Kumar, Ashok; Diaz-Mitoma, Francisco; Mestecky, Jiri

    2010-01-01

    The immune system in the gastrointestinal tract plays a crucial role in the control of infection, as it constitutes the first line of defense against mucosal pathogens. The attractive features of oral immunization have led to the exploration of a variety of oral delivery systems. However, none of these oral delivery systems have been applied to existing commercial vaccines. To overcome this, a new generation of oral vaccine delivery systems that target antigens to gut-associated lymphoid tissue is required. One promising approach is to exploit the potential of microfold (M) cells by mimicking the entry of pathogens into these cells. Targeting specific receptors on the apical surface of M cells might enhance the entry of antigens, initiating the immune response and consequently leading to protection against mucosal pathogens. In this article, we briefly review the challenges associated with current oral vaccine delivery systems and discuss strategies that might potentially target mouse and human intestinal M cells. PMID:21085599

  11. Next generation vaccines.

    PubMed

    Riedmann, Eva M

    2011-07-01

    In February this year, about 100 delegates gathered for three days in Vienna (Austria) for the Next Generation Vaccines conference. The meeting held in the Vienna Hilton Hotel from 23rd-25th February 2011 had a strong focus on biotech and industry. The conference organizer Jacob Fleming managed to put together a versatile program ranging from the future generation of vaccines to manufacturing, vaccine distribution and delivery, to regulatory and public health issues. Carefully selected top industry experts presented first-hand experience and shared solutions for overcoming the latest challenges in the field of vaccinology. The program also included several case study presentations on novel vaccine candidates in different stages of development. An interactive pre-conference workshop as well as interactive panel discussions during the meeting allowed all delegates to gain new knowledge and become involved in lively discussions on timely, interesting and sometimes controversial topics related to vaccines.

  12. Preliminary evaluation of a thermosensitive chitosan hydrogel for Echinococcus granulosus vaccine delivery.

    PubMed

    Umair, Saleh; Pernthaner, Anton; Deng, Qing; Gibson, Blake; Hook, Sarah; Heath, David

    2017-03-15

    The EG95 vaccine is effective in protecting grazing animals from infection with Echinococcus granulosus. Six male lambs were used in the study, two were each vaccinated subcutaneously with 50μg EG95/1mg Quil-A, two animals were each vaccinated with 50μg EG95/1mg Quil-A in 1% chitosan thermolabile gel subcutaneously, and two animals served as non-vaccinated controls. Two vaccinations were given at a 7 week interval. Two vaccinations induced a significantly higher antibody titre in the chitosan group compared with the Quil-A only group. The chitosan vaccine group also had a significantly higher antibody titre compared with a positive control sera from vaccinated and challenged sheep. Incorporating the EG95/Quil-A vaccine in a thermo-responsive chitosan sol-gel stimulated, after the second injection, a high level of antibody absorbance which remained high for at least one year. This response was significantly greater than the response to vaccine without the gel. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. DNA vaccination for cervical cancer: Strategic optimisation of RALA mediated gene delivery from a biodegradable microneedle system.

    PubMed

    Cole, Grace; Ali, Ahlam A; McCrudden, Cian M; McBride, John W; McCaffrey, Joanne; Robson, Tracy; Kett, Vicky L; Dunne, Nicholas J; Donnelly, Ryan F; McCarthy, Helen O

    2018-06-01

    Dissolvable microneedles can be employed to deliver DNA to antigen presenting cells within the skin. However, this technology faces two main challenges: the poor transfection efficacy of pDNA following release from the microneedle matrix, and the limited loading capacity of the micron-scale devices. Two-tier delivery systems combining microneedle platforms and DNA delivery vectors have increased efficacy but the challenge of increasing the loading capacity remains. This study utilised lyophilisation to increase the loading of RALA/pDNA nanoparticles within dissolvable PVA microneedles. As a result, delivery was significantly enhanced in vivo into an appropriate range for DNA vaccination (∼50 μg per array). Furthermore, modifying the manufacturing process was not detrimental to the microneedle mechanical properties or cargo functionality. It was demonstrated that arrays retained mechanical and functional stability over short term storage, and were able to elicit gene expression in vitro and in vivo. Finally, treatment with this novel formulation significantly retarded the growth of established tumours, and proved superior to standard intramuscular injection in a preclinical model of cervical cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Bacteriophage T4 as a Nanoparticle Platform to Display and Deliver Pathogen Antigens: Construction of an Effective Anthrax Vaccine.

    PubMed

    Tao, Pan; Li, Qin; Shivachandra, Sathish B; Rao, Venigalla B

    2017-01-01

    Protein-based subunit vaccines represent a safer alternative to the whole pathogen in vaccine development. However, limitations of physiological instability and low immunogenicity of such vaccines demand an efficient delivery system to stimulate robust immune responses. The bacteriophage T4 capsid-based antigen delivery system can robustly elicit both humoral and cellular immune responses without any adjuvant. Therefore, it offers a strong promise as a novel antigen delivery system. Currently Bacillus anthracis, the causative agent of anthrax, is a serious biothreat agent and no FDA-approved anthrax vaccine is available for mass vaccination. Here, we describe a potential anthrax vaccine using a T4 capsid platform to display and deliver the 83 kDa protective antigen, PA, a key component of the anthrax toxin. This T4 vaccine platform might serve as a universal antigen delivery system that can be adapted to develop vaccines against any infectious disease.

  15. Achieving high coverage in Rwanda's national human papillomavirus vaccination programme.

    PubMed

    Binagwaho, Agnes; Wagner, Claire M; Gatera, Maurice; Karema, Corine; Nutt, Cameron T; Ngabo, Fidele

    2012-08-01

    Virtually all women who have cervical cancer are infected with the human papillomavirus (HPV). Of the 275,000 women who die from cervical cancer every year, 88% live in developing countries. Two vaccines against the HPV have been approved. However, vaccine implementation in low-income countries tends to lag behind implementation in high-income countries by 15 to 20 years. In 2011, Rwanda's Ministry of Health partnered with Merck to offer the Gardasil HPV vaccine to all girls of appropriate age. The Ministry formed a "public-private community partnership" to ensure effective and equitable delivery. Thanks to a strong national focus on health systems strengthening, more than 90% of all Rwandan infants aged 12-23 months receive all basic immunizations recommended by the World Health Organization. In 2011, Rwanda's HPV vaccination programme achieved 93.23% coverage after the first three-dose course of vaccination among girls in grade six. This was made possible through school-based vaccination and community involvement in identifying girls absent from or not enrolled in school. A nationwide sensitization campaign preceded delivery of the first dose. Through a series of innovative partnerships, Rwanda reduced the historical two-decade gap in vaccine introduction between high- and low-income countries to just five years. High coverage rates were achieved due to a delivery strategy that built on Rwanda's strong vaccination system and human resources framework. Following the GAVI Alliance's decision to begin financing HPV vaccination, Rwanda's example should motivate other countries to explore universal HPV vaccine coverage, although implementation must be tailored to the local context.

  16. Intradermal vaccination using the novel microneedle device MicronJet600: Past, present, and future.

    PubMed

    Levin, Yotam; Kochba, Efrat; Hung, Ivan; Kenney, Richard

    2015-01-01

    Intradermal immunization has become a forefront of vaccine improvement, both scientifically and commercially. Newer technologies are being developed to address the need to reduce the dose required for vaccination and to improve the reliability and ease of injection, which have been major hurdles in expanding the number of approved vaccines using this route of administration. In this review, 7 y of clinical experience with a novel intradermal delivery device, the MicronJet600, which is a registered hollow microneedle that simplifies the delivery of liquid vaccines, are summarized. This device has demonstrated both significant dose-sparing and superior immunogenicity in various vaccine categories, as well as in diverse subject populations and age groups. These studies have shown that intradermal delivery using this device is safe, effective, and preferred by the subjects. Comparison with other intradermal devices and potential new applications for intradermal delivery that could be pursued in the future are also discussed.

  17. Intradermal vaccination using the novel microneedle device MicronJet600: Past, present, and future

    PubMed Central

    Levin, Yotam; Kochba, Efrat; Hung, Ivan; Kenney, Richard

    2015-01-01

    Intradermal immunization has become a forefront of vaccine improvement, both scientifically and commercially. Newer technologies are being developed to address the need to reduce the dose required for vaccination and to improve the reliability and ease of injection, which have been major hurdles in expanding the number of approved vaccines using this route of administration. In this review, 7 y of clinical experience with a novel intradermal delivery device, the MicronJet600, which is a registered hollow microneedle that simplifies the delivery of liquid vaccines, are summarized. This device has demonstrated both significant dose-sparing and superior immunogenicity in various vaccine categories, as well as in diverse subject populations and age groups. These studies have shown that intradermal delivery using this device is safe, effective, and preferred by the subjects. Comparison with other intradermal devices and potential new applications for intradermal delivery that could be pursued in the future are also discussed. PMID:25745830

  18. Polymer hydrogels: Chaperoning vaccines

    NASA Astrophysics Data System (ADS)

    Staats, Herman F.; Leong, Kam W.

    2010-07-01

    A cationic nanosized hydrogel (nanogel) shows controlled antigen delivery in vivo following intranasal administration and hence holds promise for a clinically effective adjuvant-free and needle-free vaccine system.

  19. Oxymetazoline plus dexpanthenol in nasal congestion.

    PubMed

    Jagade, Mohan V; Langade, Deepak G; Pophale, Rupesh R; Prabhu, Arun

    2008-12-01

    To compare the efficacy and tolerability of Oxymetazoline 0.05 % plus Dexpanthanol 5% versus Xylometazoline 0.1 % nasal drops in patients with nasal congestion due to allergic rhinitis and following nasal surgery. An investigator-blind, randomized, controlled, phase IV clinical trial conducted in 100 patients with acute allergic rhinitis or patients post-nasal surgery. Patients received either Oxymetazoline 0.05% with Dexpanthanol 5% (OD) or Xylometazoline 0.1% (XO) nasal drops. Relief from nasal congestion was significantly better in the OD group then in the XO group (mean nasal scores 1.24 vs 1.86). Significantly more improvement in sneezing and decrease in nasal discharge was seen in the OD group than the XO group. Nasal irritation in the OD group was significantly less as compared to XO group (0.38 v/s 1.12 on second day and 0.10 vs 0.36 on the fourth day). The recovery time for OD group was 1.08 hours, which was significantly (46 min) lesser than that of the XO group. Rebound congestion was significantly less in OD as compared to XO group (6.25% vs 82.98%). 93.75% of the physicians in the OD group and 51.28% in XO group reported response to therapy as good to excellent. 95.83% patients in the OD group and only 52.91% patients in the XO group rated tolerability to therapy as good to excellent. Oxymetazoline and dexpanthenol combination has a better efficacy, shorter recovery time, causes lesser rebound congestion and has better tolerability than xylometazoline.

  20. Microfabrication for Drug Delivery

    PubMed Central

    Koch, Brendan; Rubino, Ilaria; Quan, Fu-Shi; Yoo, Bongyoung; Choi, Hyo-Jick

    2016-01-01

    This review is devoted to discussing the application of microfabrication technologies to target challenges encountered in life processes by the development of drug delivery systems. Recently, microfabrication has been largely applied to solve health and pharmaceutical science issues. In particular, fabrication methods along with compatible materials have been successfully designed to produce multifunctional, highly effective drug delivery systems. Microfabrication offers unique tools that can tackle problems in this field, such as ease of mass production with high quality control and low cost, complexity of architecture design and a broad range of materials. Presented is an overview of silicon- and polymer-based fabrication methods that are key in the production of microfabricated drug delivery systems. Moreover, the efforts focused on studying the biocompatibility of materials used in microfabrication are analyzed. Finally, this review discusses representative ways microfabrication has been employed to develop systems delivering drugs through the transdermal and oral route, and to improve drug eluting implants. Additionally, microfabricated vaccine delivery systems are presented due to the great impact they can have in obtaining a cold chain-free vaccine, with long-term stability. Microfabrication will continue to offer new, alternative solutions for the development of smart, advanced drug delivery systems. PMID:28773770

  1. Thiolated chitosan nanoparticles for the nasal administration of leuprolide: bioavailability and pharmacokinetic characterization.

    PubMed

    Shahnaz, Gul; Vetter, Anja; Barthelmes, Jan; Rahmat, Deni; Laffleur, Flavia; Iqbal, Javed; Perera, Glen; Schlocker, Wolfgang; Dünnhaput, Sarah; Augustijns, Patrick; Bernkop-Schnürch, Andreas

    2012-05-30

    The purpose of this study was to develop thiolated nanoparticles to enhance the bioavailability for the nasal application of leuprolide. Thiolated chitosan-thioglycolic acid (chitosan-TGA) and unmodified chitosan nanoparticles (NPs) were developed via ionic gelation with tripolyphosphate (TPP). Leuprolide was incorporated during the formulation process of NPs. The thiolated (chitosan-TGA) NPs had a mean size of 252 ± 82 nm, a zeta potential of +10.9 ± 4 mV, and payload of leuprolide was 12 ± 2.8. Sustained release of leuprolide from thiolated NPs was demonstrated over 6h, which might be attributed to inter- and/or intramolecular disulfide formation within the NPs network. Ciliary beat frequency (CBF) study demonstrated that thiolated NPs can be considered as suitable additives for nasal drug delivery systems. Compared to leuprolide solution, unmodified NPs and thiolated NPs provoked increased leuprolide transport through porcine nasal mucosa by 2.0 and 5.2 folds, respectively. The results of a pharmacokinetic study in male Sprague-Dawley rats showed improved transport of leuprolide from thiolated NPs as compared to leuprolide solution. Thiolated NPs had a 6.9-fold increase in area under the curve, more than 4-fold increase in elimination half-life, and a ∼3.8-fold increase in maximum plasma concentration compared to nasal solution alone. The relative nasal bioavailability (versus s.c. injection) of leuprolide thiolated NPs calculated on the basis of AUC((0-6)) was about 19.6% as compared to leuprolide solution 2.8%. The enhanced bioavailability of leuprolide is likely due to facilitated transport by thiolated NPs rather than improved release. Copyright © 2012. Published by Elsevier B.V.

  2. A history of adolescent school based vaccination in Australia.

    PubMed

    Ward, Kirsten; Quinn, Helen; Menzies, Robert; McIntyre, Peter

    2013-06-30

    As adolescents have become an increasingly prominent target group for vaccination, school-based vaccination has emerged as an efficient and effective method of delivering nationally recommended vaccines to this often hard to reach group. School-based delivery of vaccines has occurred in Australia for over 80 years and has demonstrated advantages over primary care delivery for this part of the population. In the last decade school-based vaccination programs have become routine practice across all Australian states and territories. Using existing records and the recollection of experts we have compiled a history of school-based vaccination in Australia, primarily focusing on adolescents. This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney General's Department, Robert Garran Offices, National Circuit, Barton ACT 2600 or posted at http://www.ag.gov.au/cca.

  3. Drug delivery.

    PubMed

    Le Souëf, Peter N

    2002-09-16

    What we know: In preschool children, small-volume spacers perform better than large-volume spacers. Detergent is the best antistatic agent for spacers, increasing lung delivery two- to threefold, but it must not be rinsed off. A mouthpiece should be used in children aged 2-3 years or older, as lung delivery is two- to threefold higher for oral inhalation than nasal inhalation (ie, by mask). Inhaled drug doses do not generally need to be reduced in infants and young children owing to inefficiencies of delivery in younger patients. Nebulisers are "dinosaurs" and not needed for most children with asthma. What we need to know: What is the best inhalation technique for spacers? How long should children breathe, how many breaths should they take, and at what age should they breath-hold? How should children, parents and doctors be instructed to achieve optimal levels of electrostatic charge reduction for spacers? How much should inhaled steroid dose be reduced when a spacer is used optimally? What dosing instructions should be given for beta(2)-agonists delivered by spacer?

  4. Community pharmacies as sites of adult vaccination: A systematic review.

    PubMed

    Burson, Randall C; Buttenheim, Alison M; Armstrong, Allison; Feemster, Kristen A

    2016-12-01

    Vaccine-preventable deaths among adults remain a major public health concern, despite continued efforts to increase vaccination rates in this population. Alternative approaches to immunization delivery may help address under-vaccination among adults. This systematic review assesses the feasibility, acceptability, and effectiveness of community pharmacies as sites for adult vaccination. We searched 5 electronic databases (PubMed, EMBASE, Scopus, Cochrane, LILACS) for studies published prior to June 2016 and identified 47 relevant articles. We found that pharmacy-based immunization services (PBIS) have been facilitated by state regulatory changes and training programs that allow pharmacists to directly provide vaccinations. These services are widely accepted by both patients and pharmacy staff, and are capable of improving access and increasing vaccination rates. However, political and organizational barriers limit the feasibility and effectiveness of vaccine delivery in pharmacies. These studies provide evidence to inform policy and organizational efforts that promote the efficacy and sustainability of PBIS.

  5. Community pharmacies as sites of adult vaccination: A systematic review

    PubMed Central

    Burson, Randall C.; Buttenheim, Alison M.; Armstrong, Allison; Feemster, Kristen A.

    2016-01-01

    ABSTRACT Vaccine-preventable deaths among adults remain a major public health concern, despite continued efforts to increase vaccination rates in this population. Alternative approaches to immunization delivery may help address under-vaccination among adults. This systematic review assesses the feasibility, acceptability, and effectiveness of community pharmacies as sites for adult vaccination. We searched 5 electronic databases (PubMed, EMBASE, Scopus, Cochrane, LILACS) for studies published prior to June 2016 and identified 47 relevant articles. We found that pharmacy-based immunization services (PBIS) have been facilitated by state regulatory changes and training programs that allow pharmacists to directly provide vaccinations. These services are widely accepted by both patients and pharmacy staff, and are capable of improving access and increasing vaccination rates. However, political and organizational barriers limit the feasibility and effectiveness of vaccine delivery in pharmacies. These studies provide evidence to inform policy and organizational efforts that promote the efficacy and sustainability of PBIS. PMID:27715409

  6. Egg quality in laying hens exposed to Mycoplasma gallisepticum F-strain attenuated vaccine.

    PubMed

    Machado, L D S; Santos, F F D; Togashi, C K; Abreu, D L D C; Pimentel, J C; Sesti, L; Pereira, V L D A; Nascimento, E R D

    2017-04-01

    Mycoplasma gallisepticum causes coughing, ocular and nasal discharge, reduction in feed intake, lower and uneven growth, decline in egg production and quality, and increase in mortality. Among the attenuated vaccination strains, MGF can reduce clinical signs and lesions in layer hens, stimulate immune responses of cellular and humoral basis, act as an instrument of competitive exclusion in relation to field strains, and reduce the use of antimicrobials. This study aimed to investigate the effects of attenuated MG F-strain vaccination on egg quality in 3 groups of 30 hens each, being one control and 2 vaccinated. Vaccination was applied by ocular route at 8 and 12 wk of age. Comparisons were made among unvaccinated hens; vaccinated at 8 wk of age; and vaccinated at 8 and 12 wk of age. There were no statistical differences in eggshell thickness and weight among groups. Eggs from twice vaccinated birds yielded a Haugh unit significantly lower than the other groups without affecting egg classification. There was no significant difference in ELISA results between the vaccinated groups. © 2016 Poultry Science Association Inc.

  7. Development of thiolated poly(acrylic acid) microparticles for the nasal administration of exenatide.

    PubMed

    Millotti, Gioconda; Vetter, Anja; Leithner, Katharina; Sarti, Federica; Shahnaz Bano, Gul; Augustijns, Patrick; Bernkop-Schnürch, Andreas

    2014-12-01

    The purpose of this study was to develop a microparticulate formulation for nasal delivery of exenatide utilizing a thiolated polymer. Poly(acrylic acid)-cysteine (PAA-cys) and unmodified PAA microparticles loaded with exenatide were prepared via coprecipitation of the drug and the polymer followed by micronization. Particle size, drug load and release of incorporated exenatide were evaluated. Permeation enhancing properties of the formulations were investigated on excised porcine respiratory mucosa. The viability of the mucosa was investigated by histological studies. Furthermore, ciliary beat frequency (CBF) studies were performed. Microparticles displayed a mean size of 70-80 µm. Drug encapsulation was ∼80% for both thiolated and non-thiolated microparticles. Exenatide was released from both thiolated and non-thiolated particles in comparison to exenatide in buffer only within 40 min. As compared to exenatide dissolved in buffer only, non-thiolated and thiolated microparticles resulted in a 2.6- and 4.7-fold uptake, respectively. Histological studies performed before and after permeation studies showed that the mucosa is not damaged during permeation studies. CBF studies showed that the formulations were cilio-friendly. Based on these results, poly(acrylic acid)-cysteine-based microparticles seem to be a promising approach starting point for the nasal delivery of exenatide.

  8. Progress towards development of an HIV vaccine: report of the AIDS Vaccine 2009 Conference.

    PubMed

    Ross, Anna Laura; Bråve, Andreas; Scarlatti, Gabriella; Manrique, Amapola; Buonaguro, Luigi

    2010-05-01

    The search for an HIV/AIDS vaccine is steadily moving ahead, generating and validating new concepts in terms of novel vectors for antigen delivery and presentation, new vaccine and adjuvant strategies, alternative approaches to design HIV-1 antigens for eliciting protective cross-neutralising antibodies, and identification of key mechanisms in HIV infection and modulation of the immune system. All these different perspectives are contributing to the unprecedented challenge of developing a protective HIV-1 vaccine. The high scientific value of this massive effort is its great impact on vaccinology as a whole, providing invaluable scientific information for the current and future development of new preventive vaccine as well as therapeutic knowledge-based infectious-disease and cancer vaccines. Copyright 2010 Elsevier Ltd. All rights reserved.

  9. Pulmonary delivery of respiratory syncytial virus DNA vaccines using macroaggregated albumin particles.

    PubMed

    Harcourt, Jennifer L; Anderson, Larry J; Sullender, Wayne; Tripp, Ralph A

    2004-06-02

    At present there is no safe and effective vaccine for respiratory syncytial virus (RSV). DNA vaccines encoding RSV surface glycoproteins are one option being examined. Current methods to deliver DNA vaccines generally require repeated high dose intramuscular or intradermal administration for effectiveness. In this study, we examine the efficacy of pulmonary DNA vaccination using low dose DNA vaccines encoding the RSV F glycoprotein conjugated to macroaggregated albumin (MAA-F). Single vaccination of BALB/c mice with 1 microg MAA-F was ineffective, however mice boosted with an additional 1 microg MAA-F, or vaccinated a single time with 10 microg MAA-F, developed substantially improved immunity associated with reduced viral titers, increased anti-F antibody responses, and enhanced Th1 and Th2 intracellular cytokine responses. This study shows that MAA may be a useful carrier for RSV DNA vaccines.

  10. Nasal dermoid sinus cyst.

    PubMed

    Cauchois, R; Laccourreye, O; Bremond, D; Testud, R; Küffer, R; Monteil, J P

    1994-08-01

    Nasal dermoid sinus cyst is one of the diagnoses of midline nasal masses in children. This retrospective study analyzes the various theories regarding the origin of this congenital abnormality, the differential diagnosis, and the value of magnetic resonance imaging, as well as the various surgical options available.

  11. One size does not fit all: The impact of primary vaccine container size on vaccine distribution and delivery.

    PubMed

    Haidari, Leila A; Wahl, Brian; Brown, Shawn T; Privor-Dumm, Lois; Wallman-Stokes, Cecily; Gorham, Katie; Connor, Diana L; Wateska, Angela R; Schreiber, Benjamin; Dicko, Hamadou; Jaillard, Philippe; Avella, Melanie; Lee, Bruce Y

    2015-06-22

    While the size and type of a vaccine container (i.e., primary container) can have many implications on the safety and convenience of a vaccination session, another important but potentially overlooked consideration is how the design of the primary container may affect the distribution of the vaccine, its resulting cost, and whether the vial is ultimately opened. Using our HERMES software platform, we developed a simulation model of the World Health Organization Expanded Program on Immunization supply chain for the Republic of Benin and used the model to explore the effects of different primary containers for various vaccine antigens. Replacing vaccines with presentations containing fewer doses per vial reduced vaccine availability (proportion of people arriving for vaccines who are successfully immunized) by as much as 13% (from 73% at baseline) and raised logistics costs by up to $0.06 per dose administered (from $0.25 at baseline) due to increased bottlenecks, while reducing total costs by as much as $0.15 per dose administered (from $2.52 at baseline) due to lower open vial wastage. Primary containers with a greater number of doses per vial each improved vaccine availability by 19% and reduced logistics costs by $0.05 per dose administered, while reducing the total costs by up to $0.25 per dose administered. Changes in supply chain performance were more extreme in departments with greater constraints. Implementing a vial opening threshold reversed the direction of many of these effects. Our results show that one size may not fit all when choosing a primary vaccine container. Rather, the choice depends on characteristics of the vaccine, the vaccine supply chain, immunization session size, and goals of decision makers. In fact, the optimal vial size may vary among locations within a country. Simulation modeling can help identify tailored approaches to improve availability and efficiency. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. One Size Does Not Fit All: The Impact of Primary Vaccine Container Size on Vaccine Distribution and Delivery

    PubMed Central

    Haidari, Leila A.; Wahl, Brian; Brown, Shawn T.; Privor-Dumm, Lois; Wallman-Stokes, Cecily; Gorham, Katie; Connor, Diana L.; Wateska, Angela R.; Schreiber, Benjamin; Dicko, Hamadou; Jaillard, Philippe; Avella, Melanie; Lee, Bruce Y.

    2015-01-01

    BACKGROUND While the size and type of a vaccine container (i.e., primary container) can have many implications on the safety and convenience of a vaccination session, another important but potentially overlooked consideration is how the design of the primary container may affect the distribution of the vaccine, its resulting cost, and whether the vial is ultimately opened. METHODS Using our HERMES software platform, we developed a simulation model of the World Health Organization Expanded Program on Immunization supply chain for the Republic of Benin and used the model to explore the effects of different primary containers for various vaccine antigens. RESULTS Replacing vaccines with presentations containing fewer doses per vial reduced vaccine availability (proportion of people arriving for vaccines who are successfully immunized) by as much as 13% (from 73% at baseline) and raised logistics costs by up to $0.06 per dose administered (from $0.25 at baseline) due to increased bottlenecks, while reducing total costs by as much as $0.15 per dose administered (from $2.52 at baseline) due to lower open vial wastage. Primary containers with a greater number of doses per vial each improved vaccine availability by 19% and reduced logistics costs by $0.05 per dose administered, while raising the total costs by up to $0.25 per dose administered due to greater vaccine procurement needs. Changes in supply chain performance were more extreme in departments with greater constraints. Implementing a vial opening threshold reversed the direction of many of these effects. CONCLUSIONS Our results show that one size may not fit all when choosing a primary vaccine container. Rather, the choice depends on characteristics of the vaccine, the vaccine supply chain, immunization session size, and goals of decision-makers. In fact, the optimal vial size may vary among locations within a country. Simulation modeling can help identify tailored approaches to improve availability and efficiency

  13. Human papillomavirus vaccine policy and delivery in Latin America and the Caribbean.

    PubMed

    Andrus, Jon Kim; Lewis, Merle J; Goldie, Sue J; García, Patricia J; Winkler, Jennifer L; Ruiz-Matus, Cuauhtémoc; de Quadros, Ciro A

    2008-08-19

    Cervical cancer caused by human papillomavirus (HPV) is a major preventable public health problem. Two vaccines are now available for primary prevention of HPV infection and their introduction offers new opportunities to enhance comprehensive cervical cancer prevention and control. Currently, HPV vaccine price is a significant barrier to rapid vaccine introduction and access. Therefore, making evidence-based decisions about whether and how to introduce HPV vaccine into the immunization schedule in the countries of Latin America and the Caribbean (LAC) requires a rigorous analysis of several factors. These include: estimates of disease burden, cost-effectiveness, operational feasibility of reaching a population of adolescent females and other key analyses that have been used in recent years to support the introduction of other vaccines, such as rotavirus and pneumococcal conjugate vaccines. Given the large number of public health priorities that are competing for limited public resources, developing and using a sound evidence base is of particular importance for vaccines, like HPV, which are currently available only at prices higher than other vaccines now in use. HPV vaccination provides the opportunity to dramatically improve women's health and partnerships must also be broad-based and effectively coordinated. This can be achieved by developing programs based on the lessons learned from vaccination strategies used to eliminate rubella and neonatal tetanus and for scaling up influenza vaccination in countries of LAC.

  14. Biodegradable polymeric microsphere-based vaccines and their applications in infectious diseases

    PubMed Central

    Lin, Chi-Ying; Lin, Shih-Jie; Yang, Yi-Chen; Wang, Der-Yuan; Cheng, Hwei-Fang; Yeh, Ming-Kung

    2015-01-01

    Vaccination, which provides effective, safe infectious disease protection, is among the most important recent public health and immunological achievements. However, infectious disease remains the leading cause of death in developing countries because several vaccines require repeated administrations and children are often incompletely immunized. Microsphere-based systems, providing controlled release delivery, can obviate the need for repeat immunizations. Here, we review the function of sustained and pulsatile release of biodegradable polymeric microspheres in parenteral and mucosal single-dose vaccine administration. We also review the active-targeting function of polymeric particles. With their shield and co-delivery functions, polymeric particles are applied to develop single-dose and mucosally administered vaccines as well as to improve subunit vaccines. Because polymeric particles are easily surface-modified, they have been recently used in vaccine development for cancers and many infectious diseases without effective vaccines (e.g., human immunodeficiency virus infection). These polymeric particle functions yield important vaccine carriers and multiple benefits. PMID:25839217

  15. Biodegradable polymeric microsphere-based vaccines and their applications in infectious diseases.

    PubMed

    Lin, Chi-Ying; Lin, Shih-Jie; Yang, Yi-Chen; Wang, Der-Yuan; Cheng, Hwei-Fang; Yeh, Ming-Kung

    2015-01-01

    Vaccination, which provides effective, safe infectious disease protection, is among the most important recent public health and immunological achievements. However, infectious disease remains the leading cause of death in developing countries because several vaccines require repeated administrations and children are often incompletely immunized. Microsphere-based systems, providing controlled release delivery, can obviate the need for repeat immunizations. Here, we review the function of sustained and pulsatile release of biodegradable polymeric microspheres in parenteral and mucosal single-dose vaccine administration. We also review the active-targeting function of polymeric particles. With their shield and co-delivery functions, polymeric particles are applied to develop single-dose and mucosally administered vaccines as well as to improve subunit vaccines. Because polymeric particles are easily surface-modified, they have been recently used in vaccine development for cancers and many infectious diseases without effective vaccines (e.g., human immunodeficiency virus infection). These polymeric particle functions yield important vaccine carriers and multiple benefits.

  16. An overview on the role of silica-based materials in vaccine development.

    PubMed

    Navarro-Tovar, Gabriela; Palestino, Gabriela; Rosales-Mendoza, Sergio

    2016-11-01

    Although vaccination has prevented millions of deaths, the development of highly immunogenic subunit vaccines is still required. Since the number of adjuvants approved for human use is limited, the new paths for the development of delivery vehicles offered by nanotechnology are of key relevance. Areas covered: Herein, the potential of silica nanoparticles (SP) as both adjuvants and vaccine delivery vehicles is discussed based on the analysis of the current biomedical literature. Expert commentary: SP are reported not only as biodegradable and biocompatible material but also as easy to modify and with a low production cost. Additionally, several reports suggest that SP enhance the immune response. Therefore, SP are a promising delivery vehicle and/or adjuvant in vaccines. However, knowledge on the industrial production and specific aspects of immunity are still required.

  17. Nasal continuous positive airway pressure treatment: current realities and future.

    PubMed

    Berthon-Jones, M; Lawrence, S; Sullivan, C E; Grunstein, R

    1996-11-01

    Nasal continuous positive airway pressure (CPAP) is a highly effective treatment for obstructive sleep apnea syndrome. The apnea/hypopnea index (AHI) is reduced 10-fold, but the patient dropout rate is up to 30%, and usage is typically < 5 hours per night. Titration, designed to make the best trade-off between effectiveness and side effects, is expensive. Autotitrating devices make this trade-off on a minute-by-minute basis, potentially reducing mean pressure delivery, reducing side effects, and increasing compliance. The aim of this study was to test the effectiveness of the AutoSet self-adjusting nasal CPAP system (ResMed, Sydney, Australia) in eliminating obstructive events and normalizing the arousal index. Forty-five subjects (41 males and 4 females with AHI) values of > 20/hour were recruited, with written informed consent. Subjects slept for a diagnostic night, followed by a treatment night, in the laboratory, using the AutoSet system with full polysomnographic monitoring of respiratory and sleep variables. Arousals were scored using ASDA criteria. Hypopneas were scored when there was a 50% reduction in ventilation for > 10 seconds, associated with a 4% drop in oxygen saturation. For comparison, the ASDA arousal index in 16 normal subjects (without nasal CPAP) is provided. Results are given as mean +/- standard error of the mean. AHI was reduced from 55 +/- 3 to 1.5 +/- 0.35 events/hour (p < 0.0001). The arousal index was reduced from 65 +/- 3 to 18 +/- 2 events/hour (p < 0.0001), identical to the value in the 16 healthy normal subjects. There was a 158% +/- 21% increase in slow-wave sleep (p = 0.01) and a 186% +/- 27% increase in rapid eye movement sleep (p = 0.013). The AutoSet self-adjusting nasal CPAP system adequately treats obstructive sleep apnea syndrome on the first night under laboratory conditions.

  18. Speech rate reduction and "nasality" in normal speakers.

    PubMed

    Brancewicz, T M; Reich, A R

    1989-12-01

    This study explored the effects of reduced speech rate on nasal/voice accelerometric measures and nasality ratings. Nasal/voice accelerometric measures were obtained from normal adults for various speech stimuli and speaking rates. Stimuli included three sentences (one obstruent-loaded, one semivowel-loaded, and one containing a single nasal), and /pv/ syllable trains.. Speakers read the stimuli at their normal rate, half their normal rate, and as slowly as possible. In addition, a computer program paced each speaker at rates of 1, 2, and 3 syllables per second. The nasal/voice accelerometric values revealed significant stimulus effects but no rate effects. The nasality ratings of experienced listeners, evaluated as a function of stimulus and speaking rate, were compared to the accelerometric measures. The nasality scale values demonstrated small, but statistically significant, stimulus and rate effects. However, the nasality percepts were poorly correlated with the nasal/voice accelerometric measures.

  19. Evaluation of oral and subcutaneous delivery of an experimental canarypox recombinant canine distemper vaccine in the Siberian polecate (Mustela eversmanni)

    USGS Publications Warehouse

    Wimsatt, Jeffrey; Biggins, Dean E.; Innes, Kim; Taylor, Bobbi; Garell, Della

    2003-01-01

    the treatment groups. Survival rates were higher in animals with increasing serum neutralization titers (P = 0.027). This study demonstrates the efficacy of oral delivery of a recombinant CDV vaccine in the Siberian polecat. Further studies are needed to evaluate the safety and efficacy of vectored recombinant vaccines in highly susceptible species and especially in those species in which vaccination with modified live CDV has led to disease.

  20. Evaluation of oral and subcutaneous delivery of an experimental canarypox recombinant canine distemper vaccine in the Siberian polecat (Mustela eversmanni).

    PubMed

    Wimsatt, Jeffrey; Biggins, Dean; Innes, Kim; Taylor, Bobbi; Garell, Della

    2003-03-01

    any of the treatment groups. Survival rates were higher in animals with increasing serum neutralization titers (P = 0.027). This study demonstrates the efficacy of oral delivery of a recombinant CDV vaccine in the Siberian polecat. Further studies are needed to evaluate the safety and efficacy of vectored recombinant vaccines in highly susceptible species and especially in those species in which vaccination with modified live CDV has led to disease.