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Sample records for peptide-based vaccine exacerbates

  1. Peptide-based vaccines for cancer therapy

    PubMed Central

    Parmiani, Giorgio; Russo, Vincenzo; Maccalli, Cristina; Parolini, Danilo; Rizzo, Nathalie; Maio, Michele

    2014-01-01

    Interest for cancer vaccination started more than 30 years ago after the demonstration that both in animal models and later on in patients it is possible to generate anti-tumor immune responses. The clinical application of this knowledge, however, was disappointing. In this review we summarize results on peptides epitopes recognized by T cells that have been studied thanks to their easy synthesis and the lack of significant side effects when administered in-vivo. To improve the clinical efficacy, peptides were modified in their aminoacid sequence to augment their immunogenicity. Peptides vaccines were recently shown to induce a high frequency of immune response in patients that were accompanied by clinical efficacy. These data are discussed at the light of recent progression of immunotherapy caused by the addition of check-point antibodies thus providing a general picture of the potential therapeutic efficacy of the peptide-based vaccines and their combination with other biological agents. PMID:25483658

  2. Peptide-based vaccines for cancer therapy.

    PubMed

    Parmiani, Giorgio; Russo, Vincenzo; Maccalli, Cristina; Parolini, Danilo; Rizzo, Nathalie; Maio, Michele

    2014-01-01

    Interest for cancer vaccination started more than 30 years ago after the demonstration that both in animal models and later on in patients it is possible to generate anti-tumor immune responses. The clinical application of this knowledge, however, was disappointing. In this review we summarize results on peptides epitopes recognized by T cells that have been studied thanks to their easy synthesis and the lack of significant side effects when administered in-vivo. To improve the clinical efficacy, peptides were modified in their aminoacid sequence to augment their immunogenicity. Peptides vaccines were recently shown to induce a high frequency of immune response in patients that were accompanied by clinical efficacy. These data are discussed at the light of recent progression of immunotherapy caused by the addition of check-point antibodies thus providing a general picture of the potential therapeutic efficacy of the peptide-based vaccines and their combination with other biological agents. PMID:25483658

  3. Trial Watch: Peptide-based anticancer vaccines

    PubMed Central

    Pol, Jonathan; Bloy, Norma; Buqué, Aitziber; Eggermont, Alexander; Cremer, Isabelle; Sautès-Fridman, Catherine; Galon, Jérôme; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2015-01-01

    Malignant cells express antigens that can be harnessed to elicit anticancer immune responses. One approach to achieve such goal consists in the administration of tumor-associated antigens (TAAs) or peptides thereof as recombinant proteins in the presence of adequate adjuvants. Throughout the past decade, peptide vaccines have been shown to mediate antineoplastic effects in various murine tumor models, especially when administered in the context of potent immunostimulatory regimens. In spite of multiple limitations, first of all the fact that anticancer vaccines are often employed as therapeutic (rather than prophylactic) agents, this immunotherapeutic paradigm has been intensively investigated in clinical scenarios, with promising results. Currently, both experimentalists and clinicians are focusing their efforts on the identification of so-called tumor rejection antigens, i.e., TAAs that can elicit an immune response leading to disease eradication, as well as to combinatorial immunostimulatory interventions with superior adjuvant activity in patients. Here, we summarize the latest advances in the development of peptide vaccines for cancer therapy. PMID:26137405

  4. Epitope prediction algorithms for peptide-based vaccine design.

    PubMed

    Florea, Liliana; Halldórsson, Bjarni; Kohlbacher, Oliver; Schwartz, Russell; Hoffman, Stephen; Istrail, Sorin

    2003-01-01

    Peptide-based vaccines, in which small peptides derived from target proteins (eptiopes) are used to provoke an immune reaction, have attracted considerable attention recently as a potential means both of treating infectious diseases and promoting the destruction of cancerous cells by a patient's own immune system. With the availability of large sequence databases and computers fast enough for rapid processing of large numbers of peptides, computer aided design of peptide-based vaccines has emerged as a promising approach to screening among billions of possible immune-active peptides to find those likely to provoke an immune response to a particular cell type. In this paper, we describe the development of three novel classes of methods for the prediction problem. We present a quadratic programming approach that can be trained on quantitative as well as qualitative data. The second method uses linear programming to counteract the fact that our training data contains mostly positive examples. The third class of methods uses sequence profiles obtained by clustering known epitopes to score candidate peptides. By integrating these methods, using a simple voting heuristic, we achieve improved accuracy over the state of the art. PMID:16826643

  5. The present status and future prospects of peptide-based cancer vaccines.

    PubMed

    Hirayama, Masatoshi; Nishimura, Yasuharu

    2016-07-01

    Tumor cells commonly express several antigens, such as tumor-associated antigens (TAAs) or mutation-derived antigens (neoantigens), that can be regarded as foreign antigens and elicit anti-tumor immune responses in cancer patients. Various TAAs or neoantigens expressed in cancer cells have been identified and utilized as targets for cancer vaccines. One approach to elicit tumor-specific immune responses is termed peptide-based cancer vaccination; it involves administrating TAAs or neoantigen-derived peptide for treatment of cancers. There have been several forms of peptide-based cancer vaccines depending on which effector cells, such as CTLs or CD4(+) T-helper cells, are targeted to be activated. Many phase I and II clinical trials of peptide-based cancer vaccines using TAA-derived CTL epitopes, T-helper cell epitopes or dendritic cells loaded with TAA-derived peptides for various malignant tumors have been conducted and provide clinical benefits in a small fraction of patients. Nowadays, to improve the efficiency of peptide-based cancer vaccines, combination immunotherapy of peptide-based cancer vaccines with the immune-checkpoint blockade therapies using mAbs specific for CTLA-4, programmed cell death 1 (PD-1), or PD-1 ligand 1 (PD-L1) have been developed for clinical application. Furthermore, along with the recent technological progress in genetic and bioinformatic analysis, it has become easier to identify neoantigens from individual cancer patients. It is expected that peptide-based cancer vaccines targeting neoantigens as a personalized cancer immunotherapy will be developed. PMID:27235694

  6. Recent progress in adjuvant discovery for peptide-based subunit vaccines

    PubMed Central

    Azmi, Fazren; Ahmad Fuaad, Abdullah Al Hadi; Skwarczynski, Mariusz; Toth, Istvan

    2014-01-01

    Peptide-based subunit vaccines are of great interest in modern immunotherapy as they are safe, easy to produce and well defined. However, peptide antigens produce a relatively weak immune response, and thus require the use of immunostimulants (adjuvants) for optimal efficacy. Developing a safe and effective adjuvant remains a challenge for peptide-based vaccine design. Recent advances in immunology have allowed researchers to have a better understanding of the immunological implication of related diseases, which facilitates more rational design of adjuvant systems. Understanding the molecular structure of the adjuvants allows the establishment of their structure-activity relationships which is useful for the development of next-generation adjuvants. This review summarizes the current state of adjuvants development in the field of synthetic peptide-based vaccines. The structural, chemical and biological properties of adjuvants associated with their immunomodulatory effects are discussed. PMID:24300669

  7. Peptide-Based Subunit Vaccine against Hookworm Infection

    PubMed Central

    Khoshnejad, Makan; Chandrudu, Saranya; Pearson, Mark S.; Loukas, Alex; Toth, Istvan

    2012-01-01

    Hookworms infect more people than HIV and malaria combined, predominantly in third world countries. Treatment of infection with chemotherapy can have limited efficacy and re-infections after treatment are common. Heavy infection often leads to debilitating diseases. All these factors suggest an urgent need for development of vaccine. In an attempt to develop a vaccine targeting the major human hookworm, Necator americanus, a B-cell peptide epitope was chosen from the apical enzyme in the hemoglobin digestion cascade, the aspartic protease Na-APR-1. The A291Y alpha helical epitope is known to induce neutralizing antibodies that inhibit the enzymatic activity of Na-APR-1, thus reducing the capacity for hookworms to digest hemoglobin and obtain nutrients. A291Y was engineered such that it was flanked on both termini by a coil-promoting sequence to maintain native conformation, and subsequently incorporated into a Lipid Core Peptide (LCP) self-adjuvanting system. While A291Y alone or the chimeric epitope with or without Freund’s adjuvants induced negligible IgG responses, the LCP construct incorporating the chimeric peptide induced a strong IgG response in mice. Antibodies produced were able to bind to and completely inhibit the enzymatic activity of Na-APR-1. The results presented show that the new chimeric LCP construct can induce effective enzyme-neutralising antibodies in mice, without the help of any additional toxic adjuvants. This approach offers promise for the development of vaccines against helminth parasites of humans and their livestock and companion animals. PMID:23056500

  8. Peptide-based candidate vaccine against respiratory syncytial virus.

    PubMed

    Yusibov, Vidadi; Mett, Vadim; Mett, Valentina; Davidson, Carley; Musiychuk, Konstantin; Gilliam, Suzan; Farese, Ann; Macvittie, Thomas; Mann, Dean

    2005-03-18

    We engineered a 21-mer peptide representing amino acids 170-190 of the respiratory syncytial virus (RSV) G protein as a fusion with the Alfalfa mosaic virus (AlMV) coat protein (CP), produced recombinant AlMV particles presenting this peptide (VMR-RSV) on their surfaces and tested the immunogenicity in vitro in human dendritic cells and in vivo in non-human primates. Significant pathogen-specific immune responses were generated in both systems: (i) human dendritic cells armed with VMR-RSV generated vigorous CD4+ and CD8+ T cell responses; (ii) non-human primates that received these particles responded by mounting strong cellular and humoral immune responses. This approach may validate the use of a novel RSV vaccine delivery vehicle in humans. PMID:15755607

  9. Immunological consequences of using three different clinical/laboratory techniques of emulsifying peptide-based vaccines in incomplete Freund's adjuvant.

    PubMed

    Koh, Yi T; Higgins, Sean A; Weber, Jeffrey S; Kast, W Martin

    2006-01-01

    Incomplete Freund's adjuvant (IFA) serves as a carrier for water-in-oil emulsion (W/O) vaccines. The stability of such emulsions greatly affects vaccine safety and efficacy since continued presence of antigen depots at lymphoid organs releasing low-level antigens is known to stimulate a potent immune response and high-level systemic release of antigens can lead to tolerance. W/O emulsions for the purpose of clinical and laboratory peptide-based vaccinations have been prepared using the techniques of syringe extrusion, vortex or high-speed homogenization. There is no consensus in the field over which technique would be best to use and no immunological data are available that compare the three techniques. In this study, we compared the immune responses induced by a peptide-based vaccine prepared using vortex, syringe-extrusion and homogenization. The vaccination led to tumor rejection by mice vaccinated with the peptide-based vaccine prepared using all three techniques. The immunological data from the in vivo cytotoxicity assay showed a trend for lower responses and a higher variability and greater range in the immune responses induced by a vaccine that was emulsified by the vortex or homogenizer techniques as compared to the syringe-extrusion technique. There were statistically significant lower numbers of IFNgamma-secreting cells induced when the mice were vaccinated with a peptide-based vaccine emulsion prepared using the vortex compared to the syringe-extrusion technique. At a suboptimal vaccine dose, the mice vaccinated with a peptide-based vaccine emulsion prepared using the vortex technique had the largest tumors compared to the syringe-extrusion or the homogenizer technique. In the setting of a busy pharmacy that prepares peptide-based vaccine emulsions for clinical studies, the vortex technique can still be used but we urge investigators to take special care in their choice of mixing vessels for the vortex technique as that can influence the stability of the

  10. Peptide-Based Anti-PCSK9 Vaccines - An Approach for Long-Term LDLc Management

    PubMed Central

    Galabova, Gergana; Brunner, Sylvia; Winsauer, Gabriele; Juno, Claudia; Wanko, Bettina; Mairhofer, Andreas; Lührs, Petra; Schneeberger, Achim; von Bonin, Arne; Mattner, Frank; Schmidt, Walter; Staffler, Guenther

    2014-01-01

    Background Low Density Lipoprotein (LDL) hypercholesterolemia, and its associated cardiovascular diseases, are some of the leading causes of death worldwide. The ability of proprotein convertase subtilisin/kexin 9 (PCSK9) to modulate circulating LDL cholesterol (LDLc) concentrations made it a very attractive target for LDLc management. To date, the most advanced approaches for PCSK9 inhibition are monoclonal antibody (mAb) therapies. Although shown to lower LDLc significantly, mAbs face functional limitations because of their relatively short in vivo half-lives necessitating frequent administration. Here, we evaluated the long-term efficacy and safety of PCSK9-specific active vaccines in different preclinical models. Methods and Finding PCSK9 peptide-based vaccines were successfully selected by our proprietary technology. To test their efficacy, wild-type (wt) mice, Ldlr+/− mice, and rats were immunized with highly immunogenic vaccine candidates. Vaccines induced generation of high-affine PCSK9-specific antibodies in all species. Group mean total cholesterol (TC) concentration was reduced by up to 30%, and LDLc up to 50% in treated animals. Moreover, the PCSK9 vaccine-induced humoral immune response persisted for up to one year in mice, and reduced cholesterol levels significantly throughout the study. Finally, the vaccines were well tolerated in all species tested. Conclusions Peptide-based anti-PCSK9 vaccines induce the generation of antibodies that are persistent, high-affine, and functional for up to one year. They are powerful and safe tools for long-term LDLc management, and thus may represent a novel therapeutic approach for the prevention and/or treatment of LDL hypercholesterolemia-related cardiovascular diseases in humans. PMID:25474576

  11. Totally synthetic peptide-based immunocontraceptive vaccines show activity in dogs of different breeds.

    PubMed

    Walker, John; Ghosh, Souravi; Pagnon, Joanne; Colantoni, Caterina; Newbold, Andrea; Zeng, Weiguang; Jackson, David C

    2007-10-10

    In this study we examine the immunogenicity of totally synthetic peptide-based immunocontraceptive vaccines in dogs. Seven individual epitope-based vaccines were assembled in which a different T helper (T(H)) cell epitope derived from the sequence of F protein of canine distemper virus was synthesized in tandem with a peptide representing luteinising hormone releasing hormone (LHRH). Each of the individual T(H)-LHRH peptide vaccines was inoculated subcutaneously into dogs. The results demonstrate that five of the seven peptide vaccines were able to elicit strong anti-LHRH antibody responses in beagle foxhounds accompanied by a concomitant suppression in the levels of the hormones testosterone and progesterone in the majority of the animals. A pool of these five peptides was then used to inoculate five different breeds of dogs. All animals responded with high levels of anti-LHRH antibody. An investigation of the proliferative responses of peripheral blood mononuclear cells (PBMC) obtained from inoculated dogs showed that the majority of breeds responded to each of the individual T helper cell epitope tested. The results provide a strategy for development of an immunocontraceptive vaccine for use in multiple breeds of dogs. PMID:17825958

  12. Rational peptide-based tumour vaccine development and T cell monitoring.

    PubMed

    Scheibenbogen, Carmen; Letsch, Anne; Schmittel, Alexander; Asemissen, Anne-Marie; Thiel, Eckhard; Keilholz, Ulrich

    2003-12-01

    Antigen-specific vaccination is a promising emerging treatment option for cancer patients. Results from early clinical vaccination trials with tumour peptides in patients with metastatic disease have shown tumour regressions in few patients usually with limited disease. Current clinical studies focus on the development of more potent vaccination strategies and on the vaccination of patients with occult or small volume metastatic disease. The novel generation of sensitive T-cell assays allowing direct quantitation and characterisation of specific T cells provide an essential tool for further systematic clinical development of vaccine protocols. There is accumulating evidence from clinical cancer vaccination trials of a relation between the induction of specific T cells and clinical efficacy. PMID:15001161

  13. Exacerbation of atopic dermatitis after bacillus Calmette-Guérin vaccination.

    PubMed Central

    Dalton, S J; Haeney, M R; Patel, L; David, T J

    1998-01-01

    In two children with atopic dermatitis, routine vaccination with bacillus Calmette-Guérin (BCG) was followed by severe exacerbation of skin disease. If the sequence is cause and effect, a possible mechanism is stimulation of a Th2 lymphocyte cytokine profile by the vaccine, with migration of activated lymphocytes to inflamed skin. In children with active atopic dermatitis, BCG vaccination is best deferred until remission. PMID:9659324

  14. Structure-activity relationship of lipid core peptide-based Group A Streptococcus vaccine candidates.

    PubMed

    Chan, Amy; Hussein, Waleed M; Ghaffar, Khairunnisa Abdul; Marasini, Nirmal; Mostafa, Ahmed; Eskandari, Sharareh; Batzloff, Michael R; Good, Michael F; Skwarczynski, Mariusz; Toth, Istvan

    2016-07-15

    Infection with Group A Streptococcus (GAS) can result in a range of different illnesses, some of which are fatal. Currently, our efforts to develop a vaccine against GAS focuses on the lipid core peptide (LCP) system, a subunit vaccine containing a lipoamino acid (LAA) moiety which allows the stimulation of systemic antibody activity. In the present study, a peptide (J14) representing the B-cell epitope from the GAS M protein was incorporated alongside a universal T-helper epitope (P25) in four LCP constructs of different spatial orientation or LAA lengths. Through structure-activity studies, it was discovered that while the alteration of the LCP orientation had a weaker effect on immunostimulation, increasing the LAA side chain length within the construct increased antibody responses in murine models. Furthermore, the mice immunised with the lead LCP construct were also able to maintain antibody activity throughout the course of five months. These findings highlight the importance of LAA moieties in the development of intranasal peptide vaccines and confirmed that its side chain length has an effect on the immunogenicity of the structure. PMID:27246859

  15. TGF-β-mediated airway tolerance to allergens induced by peptide-based immunomodulatory mucosal vaccination.

    PubMed

    Michael, H; Li, Y; Wang, Y; Xue, D; Shan, J; Mazer, B D; McCusker, C T

    2015-11-01

    We sought to modulate mucosal immune responses using neonatal vaccination to avert the development of allergic airways disease (AAD). Pulmonary pathology in AAD is driven by T helper (TH)2 cytokines, in particular interleukin (IL)4 and IL13, the expression and actions of which are regulated by the transcription factor STAT6. We developed a peptide homolog of STAT6, STAT6-IP. Neonatal mice given, intranasally, STAT6-IP, in an effort to modulate de novo airways immune responses, developed tolerance following subsequent allergen sensitization, with either ovalbumin or ragweed allergens, as demonstrated by reduced TH2 cytokines and specific immunoglobulin (Ig)E and the significant increases in the latency-associated peptide (LAP)(+) T-regulatory (Treg) cell subset and expression of transforming growth factor (TGF)-β. This regulatory phenotype was transferrable by CD4(+) T cells or CD11c(+) dendritic cells (DCs) derived from STAT6-IP-vaccinated mice. Anti-TGF-β treatment during allergen sensitization, however, re-established the pro-inflammatory TH2 response. Thus, neonatal STAT6-IP vaccination induces prospective TGF-β-dependent tolerance to allergen and constitutes a novel highly effective immunomodulatory allergy prevention strategy. PMID:25783968

  16. Development and characterization of a recombinant, hypoallergenic, peptide-based vaccine for grass pollen allergy

    PubMed Central

    Focke-Tejkl, Margarete; Weber, Milena; Niespodziana, Katarzyna; Neubauer, Angela; Huber, Hans; Henning, Rainer; Stegfellner, Gottfried; Maderegger, Bernhard; Hauer, Martina; Stolz, Frank; Niederberger, Verena; Marth, Katharina; Eckl-Dorna, Julia; Weiss, Richard; Thalhamer, Josef; Blatt, Katharina; Valent, Peter; Valenta, Rudolf

    2015-01-01

    Background Grass pollen is one of the most important sources of respiratory allergies worldwide. Objective This study describes the development of a grass pollen allergy vaccine based on recombinant hypoallergenic derivatives of the major timothy grass pollen allergens Phl p 1, Phl p 2, Phl p 5, and Phl p 6 by using a peptide-carrier approach. Methods Fusion proteins consisting of nonallergenic peptides from the 4 major timothy grass pollen allergens and the PreS protein from hepatitis B virus as a carrier were expressed in Escherichia coli and purified by means of chromatography. Recombinant PreS fusion proteins were tested for allergenic activity and T-cell activation by means of IgE serology, basophil activation testing, T-cell proliferation assays, and xMAP Luminex technology in patients with grass pollen allergy. Rabbits were immunized with PreS fusion proteins to characterize their immunogenicity. Results Ten hypoallergenic PreS fusion proteins were constructed, expressed, and purified. According to immunogenicity and induction of allergen-specific blocking IgG antibodies, 4 hypoallergenic fusion proteins (BM321, BM322, BM325, and BM326) representing Phl p 1, Phl p 2, Phl p 5, and Phl p 6 were included as components in the vaccine termed BM32. BM321, BM322, BM325, and BM326 showed almost completely abolished allergenic activity and induced significantly reduced T-cell proliferation and release of proinflammatory cytokines in patients' PBMCs compared with grass pollen allergens. On immunization, they induced allergen-specific IgG antibodies, which inhibited patients' IgE binding to all 4 major allergens of grass pollen, as well as allergen-induced basophil activation. Conclusion A recombinant hypoallergenic grass pollen allergy vaccine (BM32) consisting of 4 recombinant PreS-fused grass pollen allergen peptides was developed for safe immunotherapy of grass pollen allergy. PMID:25441634

  17. Costimulation as a platform for the development of vaccines: a peptide-based vaccine containing a novel form of 4-1BB ligand eradicates established tumors.

    PubMed

    Sharma, Rajesh K; Elpek, Kutlu G; Yolcu, Esma S; Schabowsky, Rich-Henry; Zhao, Hong; Bandura-Morgan, Laura; Shirwan, Haval

    2009-05-15

    Vaccines represent an attractive treatment modality for the management of cancer primarily because of their specificity and generation of immunologic memory important for controlling recurrences. However, the efficacy of therapeutic vaccines may require formulations that not only generate effective immune responses but also overcome immune evasion mechanisms employed by progressing tumor. Costimulatory molecules play critical roles in modulating innate, adaptive, and regulatory immunity and have potential to serve as effective immunomodulatory components of therapeutic vaccines. In this study, we tested the function of a novel soluble form of 4-1BB ligand (4-1BBL) costimulatory molecule in modulating innate, adaptive, and regulatory immunity and assessed its therapeutic efficacy in the HPV-16 E7-expressing TC-1 cervical cancer and survivin-expressing 3LL lung carcinoma mouse models. Vaccination with 4-1BBL activated dendritic cells and enhanced antigen uptake, generated CD8(+) T-cell effector/memory responses, and endowed T effector cells refractory to suppression by CD4(+)CD25(+)FoxP3(+) T regulatory cells. Immunization with 4-1BBL in combination with an E7 peptide or survivin protein resulted in eradication of TC-1 and 3LL tumors, respectively. 4-1BBL was more effective than TLR agonists LPS, MPL, and CpG and an agonistic 4-1BB antibody as a component of E7 peptide-based therapeutic vaccine for the generation of immune responses and eradication of TC-1 established tumors in the absence of detectable toxicity. Therapeutic efficacy was associated with reversal of tumor-mediated nonresponsiveness/anergy as well as establishment of long-term CD8(+) T-cell memory. Potent pleiotropic immunomodulatory activities combined with lack of toxicity highlight the potential of 4-1BBL molecule as an effective component of therapeutic cancer vaccines. PMID:19435920

  18. Development of a peptide-based vaccine targeting TMPRSS2:ERG fusion positive prostate cancer

    PubMed Central

    Kissick, Haydn Thomas; Sanda, Martin George; Dunn, Laura Kathleen; Arredouani, Mohamed Simo

    2013-01-01

    Identification of novel vaccine targets is critical for the design and advancement of prostate cancer (PCa) immunotherapy. Ideal targets are proteins that are abundant in prostate tumors while absent in extra-prostatic tissues. The fusion of the androgen-regulated TMPRSS2 gene with the ETS transcription factor ERG occurs in approximately 50% of prostate cancer cases and results in aberrant ERG expression. Because expression of ERG is very low in peripheral tissue, we evaluated the suitability of this protein as an antigen target in PCa vaccines. ERG-derived HLA-A*0201-restricted immunogenic epitopes were identified through a 3-step strategy that included in silico, in vitro, and in vivo validation. Algorithms were used to predict potential HLA-A*0201-binding epitopes. High scoring epitopes were tested for binding to HLA-A*0201 using the T2-based stabilization assay in vitro. Five peptides were found to bind HLA-A*0201 and were subsequently tested for immunogenicity in humanized HLA-A*0201 transgenic mice. The in vivo screening identified three immunogenic peptides. One of these peptides, ERG295, overcame peripheral tolerance in HLA-A*0201 mice that expressed prostate restricted ERG. Also, this peptide induced an antigen specific response against ERG-expressing human prostate tumor cells. Finally, tetramer assay showed detectable and responsive ERG295-specific cytotoxic lymphocytes in peripheral blood of HLA-A*0201+ prostate cancer patients. Detection of ERG-specific CTLs in both mice and the blood of prostate cancer patients indicates that ERG-specific tolerance can be overcome. Additionally, these data suggest that ERG is a suitable target antigen for PCa immunotherapy. PMID:24149465

  19. Parametric Response Mapping of Apparent Diffusion Coefficient (ADC) as an Imaging Biomarker to Distinguish Pseudoprogression from True Tumor Progression In Peptide-Based Vaccine Therapy for Pediatric Diffuse Instrinsic Pontine Glioma

    PubMed Central

    Ceschin, Rafael; Kurland, Brenda F.; Abberbock, Shira R.; Ellingson, Benjamin M.; Okada, Hideho; Jakacki, Regina I.; Pollack, Ian F.; Panigrahy, Ashok

    2015-01-01

    Background and Purpose Immune response to cancer therapy may result in pseudoprogression, which can only be identified retrospectively and which may disrupt an effective therapy. This study assesses whether serial parametric response mapping (PRM, a voxel-by-voxel method of image analysis also known as functional diffusion mapping) analysis of ADC measurements following peptide-based vaccination may help prospectively distinguish progression from pseudoprogression in pediatric patients with diffuse intrinsic pontine gliomas. Materials and Methods From 2009–2012, 21 children age 4–18 with diffuse intrinsic pontine gliomas were enrolled in a serial peptide-based vaccination protocol following radiotherapy. DWI was acquired before immunotherapy and at six week intervals during vaccine treatment. Pseudoprogression was identified retrospectively based on clinical and radiographic findings, excluding DWI. Parametric response mapping was used to analyze 96 scans, comparing ADC measures at multiple time points (from first vaccine to up to 12 weeks after the vaccine was halted) to pre-vaccine baseline values. Log-transformed fractional increased ADC (fiADC), fractional decreased ADC (fdADC), and parametric response mapping ratio (fiADC/fdADC) were compared between patients with and without pseudoprogression, using generalized estimating equations with inverse weighting by cluster size. Results Median survival was 13.1 months from diagnosis (range 6.4–24.9 months). Four of 21 children (19%) were assessed as experiencing pseudoprogression. Patients with pseudoprogression had higher fitted average log-transformed parametric response mapping ratios (p=0.01) and fiADCs (p=0.0004), compared to patients without pseudoprogression. Conclusion Serial parametric response mapping of ADC, performed at multiple time points of therapy, may distinguish pseudoprogression from true progression in patients with diffuse intrinsic pontine gliomas treated with peptide-based vaccination

  20. Effectiveness of the influenza vaccine at preventing hospitalization due to acute exacerbation of cardiopulmonary disease in Korea from 2011 to 2012.

    PubMed

    Seo, Yu Bin; Choi, Won Suk; Baek, Ji Hyeon; Lee, Jacob; Song, Joon Young; Lee, Jin Soo; Cheong, Hee Jin; Kim, Woo Joo

    2014-01-01

    There is a lack of targeted studies to validate the effectiveness of influenza vaccination on the reduction in influenza-related hospitalizations among patients with co-morbidities. In this study, we estimate the effectiveness of influenza vaccination on preventing hospitalizations in persons with cardiopulmonary disease and establish an evidence base for recommendations on influenza vaccination in this population. During the influenza epidemic in 2011-2012, we performed a multicenter, retrospective case-control study. Cases were patients hospitalized due to acute exacerbation of asthma, COPD, ischemic heart disease (IHD), and congestive heart failure (CHF). Controls were selected from outpatients who visited study hospitals but who were not hospitalized. Cases and controls were matched 1:1 based on age, gender, and date of hospital visit. Conditional logistic regression analyses were used to determine the effectiveness of vaccination. Between 25 December 2011 and 5 May 2012, 828 of each hospitalized and control subjects were identified. The influenza vaccination rate of the hospitalized and non-hospitalized patients was 54.2% and 60.4%, respectively (P = 0.006). The overall vaccine effectiveness for preventing hospitalization was 33.7% (95% confidence interval [CI] 14.0-49.0%; P = 0.002). Conditional logistic regression analysis showed that influenza vaccination significantly reduced the risk of hospitalization, especially due to acute exacerbation of IHD and CHF, in patients aged 65 y and older. The estimated vaccine effectiveness in these patients was 56.0% (95% CI 32.1-71.4%, P = 0.002). Influenza vaccination was associated with a reduction in the risk of hospitalization due to acute exacerbation of cardiopulmonary disease. We recommend the vaccine be given primarily to patients with underlying cardiovascular disease, particularly those 65 y of age and older. PMID:24161939

  1. Recent advances in peptide-based subunit nanovaccines.

    PubMed

    Skwarczynski, Mariusz; Toth, Istvan

    2014-12-01

    Vaccination is the most efficient way to protect humans against pathogens. Peptide-based vaccines offer several advantages over classical vaccines, which utilized whole organisms or proteins. However, peptides alone are not immunogenic and need a delivery system that can boost their recognition by the immune system. In recent years, nanotechnology-based approaches have become one of the most promising strategies in peptide vaccine delivery. This review summarizes knowledge on peptide vaccines and nanotechnology-based approaches for their delivery. The recently reported nano-sized delivery platforms for peptide antigens are reviewed, including nanoparticles composed of polymers, peptides, lipids, inorganic materials and nanotubes. The future prospects for peptide-based nanovaccines are discussed. PMID:25529569

  2. Immunogenicity of a Promiscuous T Cell Epitope Peptide Based Conjugate Vaccine against Benzo[a]pyrene: Redirecting Antibodies to the Hapten

    PubMed Central

    Schellenberger, Mario T.; Grova, Nathalie; Farinelle, Sophie; Willième, Stéphanie; Revets, Dominique; Muller, Claude P.

    2012-01-01

    The prototype polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is an environmental pollutant and food contaminant of epidemiological importance. To protect against adverse effects of this ubiquitous carcinogen, we developed an immunoprophylactic strategy based on a B[a]P-protein conjugate vaccine to induce B[a]P specific antibodies (Grova et al., Vaccine. 2009;27:4142–51). Here, we investigated in mice the efficacy of B[a]P-peptide conjugates based on promiscuous T cell epitopes (TCE) into further improve this approach. We showed that B[a]P-peptide conjugates induced very different levels of hapten-specific antibodies with variable functional efficacy, depending on the carrier. In some cases peptide carriers induced a more efficient antibody response against B[a]P than tetanus toxoid as a protein carrier, with the capacity to sequester more B[a]P in the blood. Reducing the carrier size to a single TCE can dramatically shift the antibody bias from the carrier to the B[a]P. Conjugates based on the TCE FIGITEL induced the best anti-hapten response and no antibodies against the carrier peptide. Some peptide conjugates increased the selectivity of the antibodies for the activated metabolite 7,8-diol-B[a]P and B[a]P by one or two orders of magnitude. The antibody efficacy was also demonstrated in their ability to sequester B[a]P in the blood and modulate its faecal excretion (15–56%). We further showed that pre-existing immunity to the carrier from which the TCE was derived did not reduce the immunogenicity of the peptide conjugate. In conclusion, we showed that a vaccination against B[a]P using promiscuous TCEs of tetanus toxin as carriers is feasible even in case of a pre-existing immunity to the toxoid and that some TCE epitopes dramatically redirect the antibody response to the hapten. Further studies to demonstrate a long-term protection of an immunoprophylactic immunisation against B[a]P are warranted. PMID:22666501

  3. Immunogenicity of a promiscuous T cell epitope peptide based conjugate vaccine against benzo[a]pyrene: redirecting antibodies to the hapten.

    PubMed

    Schellenberger, Mario T; Grova, Nathalie; Farinelle, Sophie; Willième, Stéphanie; Revets, Dominique; Muller, Claude P

    2012-01-01

    The prototype polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is an environmental pollutant and food contaminant of epidemiological importance. To protect against adverse effects of this ubiquitous carcinogen, we developed an immunoprophylactic strategy based on a B[a]P-protein conjugate vaccine to induce B[a]P specific antibodies (Grova et al., Vaccine. 2009;27:4142-51). Here, we investigated in mice the efficacy of B[a]P-peptide conjugates based on promiscuous T cell epitopes (TCE) into further improve this approach. We showed that B[a]P-peptide conjugates induced very different levels of hapten-specific antibodies with variable functional efficacy, depending on the carrier. In some cases peptide carriers induced a more efficient antibody response against B[a]P than tetanus toxoid as a protein carrier, with the capacity to sequester more B[a]P in the blood. Reducing the carrier size to a single TCE can dramatically shift the antibody bias from the carrier to the B[a]P. Conjugates based on the TCE FIGITEL induced the best anti-hapten response and no antibodies against the carrier peptide. Some peptide conjugates increased the selectivity of the antibodies for the activated metabolite 7,8-diol-B[a]P and B[a]P by one or two orders of magnitude. The antibody efficacy was also demonstrated in their ability to sequester B[a]P in the blood and modulate its faecal excretion (15-56%). We further showed that pre-existing immunity to the carrier from which the TCE was derived did not reduce the immunogenicity of the peptide conjugate. In conclusion, we showed that a vaccination against B[a]P using promiscuous TCEs of tetanus toxin as carriers is feasible even in case of a pre-existing immunity to the toxoid and that some TCE epitopes dramatically redirect the antibody response to the hapten. Further studies to demonstrate a long-term protection of an immunoprophylactic immunisation against B[a]P are warranted. PMID:22666501

  4. A phase I dose-escalation clinical trial of a peptide-based human papillomavirus therapeutic vaccine with Candida skin test reagent as a novel vaccine adjuvant for treating women with biopsy-proven cervical intraepithelial neoplasia 2/3

    PubMed Central

    Greenfield, William W; Stratton, Shawna L; Myrick, Rebecca S; Vaughn, Rita; Donnalley, Lisa M; Coleman, Hannah N; Mercado, Maria; Moerman-Herzog, Andrea M; Spencer, Horace J; Andrews-Collins, Nancy R; Hitt, Wilbur C; Low, Gordon M; Manning, Nirvana A; McKelvey, Samantha S; Smith, Dora; Smith, Michael V; Phillips, Amy M; Quick, C Matthew; Jeffus, Susanne K; Hutchins, Laura F; Nakagawa, Mayumi

    2015-01-01

    PURPOSE: Non-surgical treatments for cervical intraepithelial neoplasia 2/3 (CIN2/3) are needed as surgical treatments have been shown to double preterm delivery rate. The goal of this study was to demonstrate safety of a human papillomavirus (HPV) therapeutic vaccine called PepCan, which consists of four current good-manufacturing production-grade peptides covering the HPV type 16 E6 protein and Candida skin test reagent as a novel adjuvant. PATIENTS AND METHODS: The study was a single-arm, single-institution, dose-escalation phase I clinical trial, and the patients (n = 24) were women with biopsy-proven CIN2/3. Four injections were administered intradermally every 3 weeks in limbs. Loop electrical excision procedure (LEEP) was performed 12 weeks after the last injection for treatment and histological analysis. Six subjects each were enrolled (50, 100, 250, and 500 μg per peptide). RESULTS: The most common adverse events (AEs) were injection site reactions, and none of the patients experienced dose-limiting toxicities. The best histological response was seen at the 50 μg dose level with a regression rate of 83% (n = 6), and the overall rate was 52% (n = 23). Vaccine-induced immune responses to E6 were detected in 65% of recipients (significantly in 43%). Systemic T-helper type 1 (Th1) cells were significantly increased after four vaccinations (P = 0.02). CONCLUSION: This study demonstrated that PepCan is safe. A significantly increased systemic level of Th1 cells suggests that Candida, which induces interleukin-12 (IL-12) in vitro, may have a Th1 promoting effect. A phase II clinical trial to assess the full effect of this vaccine is warranted. PMID:26451301

  5. Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis: protocol for a randomised controlled trial

    PubMed Central

    2013-01-01

    Background Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. Methods A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW135) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and ≥6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged ≥6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine- related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function

  6. Peptide-Based Treatment: A Promising Cancer Therapy

    PubMed Central

    Xiao, Yu-Feng; Jie, Meng-Meng; Li, Bo-Sheng; Hu, Chang-Jiang; Xie, Rui; Tang, Bo; Yang, Shi-Ming

    2015-01-01

    Many new therapies are currently being used to treat cancer. Among these new methods, chemotherapy based on peptides has been of great interest due to the unique advantages of peptides, such as a low molecular weight, the ability to specifically target tumor cells, and low toxicity in normal tissues. In treating cancer, peptide-based chemotherapy can be mainly divided into three types, peptide-alone therapy, peptide vaccines, and peptide-conjugated nanomaterials. Peptide-alone therapy may specifically enhance the immune system's response to kill tumor cells. Peptide-based vaccines have been used in advanced cancers to improve patients' overall survival. Additionally, the combination of peptides with nanomaterials expands the therapeutic ability of peptides to treat cancer by enhancing drug delivery and sensitivity. In this review, we mainly focus on the new advances in the application of peptides in treating cancer in recent years, including diagnosis, treatment, and prognosis. PMID:26568964

  7. Host response to secondary bacterial infection associated with antecedent influenza virus infection in pigs – exacerbation associated with vaccination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The increasing number of annual influenza (IAV) cases, coupled with the recent IAV pandemic, has amplified concerns about its impact on human and animal health. It is appreciated that Flu is complicated by bacterial pneumonia. Vaccine-associated enhanced respiratory disease (VAERD) can occur followi...

  8. Vaccinations

    MedlinePlus

    ... vaccinated? For many years, a set of annual vaccinations was considered normal and necessary for dogs and ... to protect for a full year. Consequently, one vaccination schedule will not work well for all pets. ...

  9. Immunization with DNA vaccines containing porcine reproductive and respiratory syndrome virus open reading frames 5, 6, and 7 may be related to the exacerbation of clinical disease after an experimental challenge.

    PubMed

    Díaz, Ivan; Ganges, Llilianne; Galindo-Cardiel, Iván; Tarradas, Joan; Alvarez, Belén; Lorca-Oró, Cristina; Pujols, Joan; Gimeno, Mariona; Darwich, Laila; Domingo, Mariano; Domínguez, Javier; Mateu, Enric

    2013-02-01

    Pigs were immunized with DNA plasmids containing different open reading frames (ORFs) of a porcine reproductive and respiratory syndrome virus (PRRSV) genotype I strain. One group was injected with three inoculations of ORF7, a second group was immunized with three inoculations of plasmids containing ORF5 and ORF6, and a third group was kept as controls. Later, +21 days after the last inoculation, animals were challenged with the homologous strain. After the challenge, PRRSV-specific interferon (IFN)-γ-secreting cells and anti-PRRSV IgG antibodies developed faster in DNA vaccinated pigs (p<0.05). However, DNA-immunized pigs showed an exacerbation of the disease compared to the unvaccinated challenged pigs. The data suggest that previous immunization with DNA vaccines against glycoprotein 5 and/or matrix protein of PRRSV, as well as nucleoprotein but to a lesser degree, could result in an exacerbation of the clinical course in terms of fever upon challenge. PMID:23409932

  10. Vaccines

    MedlinePlus Videos and Cool Tools

    Vaccinations are injections of antigens into the body. Once the antigens enter the blood, they circulate along ... suppressor T cells stop the attack. After a vaccination, the body will have a memory of an ...

  11. Dose-dependent protection against or exacerbation of disease by a polylactide glycolide microparticle-adsorbed, alphavirus-based measles virus DNA vaccine in rhesus macaques.

    PubMed

    Pan, Chien-Hsiung; Nair, Nitya; Adams, Robert J; Zink, M Christine; Lee, Eun-Young; Polack, Fernando P; Singh, Manmohan; O'Hagan, Derek T; Griffin, Diane E

    2008-04-01

    Measles remains an important cause of vaccine-preventable child mortality. Development of a low-cost, heat-stable vaccine for infants under the age of 6 months could improve measles control by facilitating delivery at the time of other vaccines and by closing a window of susceptibility prior to immunization at 9 months of age. DNA vaccines hold promise for development, but achieving protective levels of antibody has been difficult and there is an incomplete understanding of protective immunity. In the current study, we evaluated the use of a layered alphavirus DNA/RNA vector encoding measles virus H (SINCP-H) adsorbed onto polylactide glycolide (PLG) microparticles. In mice, antibody and T-cell responses to PLG-formulated DNA were substantially improved compared to those to naked DNA. Rhesus macaques received two doses of PLG/SINCP-H delivered either intramuscularly (0.5 mg) or intradermally (0.5 or 0.1 mg). Antibody and T-cell responses were induced but not sustained. On challenge, the intramuscularly vaccinated monkeys did not develop rashes and had lower viremias than vector-treated control monkeys. Monkeys vaccinated with the same dose intradermally developed rashes and viremia. Monkeys vaccinated intradermally with the low dose developed more severe rashes, with histopathologic evidence of syncytia and intense dermal and epidermal inflammation, eosinophilia, and higher viremia compared to vector-treated control monkeys. Protection after challenge correlated with gamma interferon-producing T cells and with early production of high-avidity antibody that bound wild-type H protein. We conclude that PLG/SINCP-H is most efficacious when delivered intramuscularly but does not provide an advantage over standard DNA vaccines for protection against measles. PMID:18287579

  12. [VACCINES].

    PubMed

    Bellver Capella, Vincente

    2015-10-01

    Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs. PMID:26685562

  13. Vaccines

    MedlinePlus Videos and Cool Tools

    ... help the body defend itself against foreign invaders. As the antigens invade the body's tissues, they attract ... the suppressor T cells stop the attack. After a vaccination, the body will have a memory of ...

  14. Exacerbations of COPD

    PubMed Central

    Pavord, Ian D; Jones, Paul W; Burgel, Pierre-Régis; Rabe, Klaus F

    2016-01-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) are defined as sustained worsening of a patient’s condition beyond normal day-to-day variations that is acute in onset, and that may also require a change in medication and/or hospitalization. Exacerbations have a significant and prolonged impact on health status and outcomes, and negative effects on pulmonary function. A significant proportion of exacerbations are unreported and therefore left untreated, leading to a poorer prognosis than those treated. COPD exacerbations are heterogeneous, and various phenotypes have been proposed which differ in biologic basis, prognosis, and response to therapy. Identification of biomarkers could enable phenotype-driven approaches for the management and prevention of exacerbations. For example, several biomarkers of inflammation can help to identify exacerbations most likely to respond to oral corticosteroids and antibiotics, and patients with a frequent exacerbator phenotype, for whom preventative treatment is appropriate. Reducing the frequency of exacerbations would have a beneficial impact on patient outcomes and prognosis. Preventative strategies include modification of risk factors, treatment of comorbid conditions, the use of bronchodilator therapy with long-acting β2-agonists or long-acting muscarinic antagonists, and inhaled corticosteroids. A better understanding of the mechanisms underlying COPD exacerbations will help to optimize use of the currently available and new interventions for preventing and treating exacerbations. PMID:26937187

  15. Amyloid-Peptide Vaccinations Reduce β-Amyloid Plaques but Exacerbate Vascular Deposition and Inflammation in the Retina of Alzheimer’s Transgenic Mice

    PubMed Central

    Liu, Bingqian; Rasool, Suhail; Yang, Zhikuan; Glabe, Charles G.; Schreiber, Steven S.; Ge, Jian; Tan, Zhiqun

    2009-01-01

    Alzheimer’s disease (AD) is pathologically characterized by accumulation of β-amyloid (Aβ) protein deposits and/or neurofibrillary tangles in association with progressive cognitive deficits. Although numerous studies have demonstrated a relationship between brain pathology and AD progression, the Alzheimer’s pathological hallmarks have not been found in the AD retina. A recent report showed Aβ plaques in the retinas of APPswe/PS1ΔE9 transgenic mice. We now report the detection of Aβ plaques with increased retinal microvascular deposition of Aβ and neuroinflammation in Tg2576 mouse retinas. The majority of Aβ-immunoreactive plaques were detected from the ganglion cell layer to the inner plexiform layer, and some plaques were observed in the outer nuclear layer, photoreceptor outer segment, and optic nerve. Hyperphosphorylated tau was labeled in the corresponding areas of the Aβ plaques in adjacent sections. Although Aβ vaccinations reduced retinal Aβ deposits, there was a marked increase in retinal microvascular Aβ deposition as well as local neuroinflammation manifested by microglial infiltration and astrogliosis linked with disruption of the retinal organization. These results provide evidence to support further investigation of the use of retinal imaging to diagnose AD and to monitor disease activity. PMID:19834067

  16. Antimicrobial peptide-based treatment for endodontic infections--biotechnological innovation in endodontics.

    PubMed

    Lima, Stella Maris de Freitas; de Pádua, Gabriela Martins; Sousa, Maurício Gonçalves da Costa; Freire, Mirna de Souza; Franco, Octávio Luiz; Rezende, Taia Maria Berto

    2015-01-01

    The presence/persistence of microorganisms in the pulp and periapical area corresponds to the maintenance of an exacerbated immune response that leads to the start of periradicular bone resorption and its perpetuation. In endodontic treatment, the available intracanal medications do not have all the desirable properties in the context of endodontic infection and apical periodontitis; they need to include not only strong antimicrobial performance but also an immunomodulatory and reparative activity, without host damage. In addition, there are various levels of resistance to root canal medications. Thus, antimicrobial agents that effectively eliminate resistant species in root canals could potentially improve endodontic treatment. In the emergence of new therapies, an increasing number of studies on antimicrobial peptides (AMPs) have been seen over the past few years. AMPs are defense biomolecules produced in response to infection, and they have a wide spectrum of action against many oral microorganisms. There are some studies that correlate peptides and oral infections, including oral peptides, neuropeptides, and bacterial, fish, bovine and synthetic peptides. So far, there are around 120 published studies correlating endodontic microbiota with AMPs but, according to our knowledge, there are no registered patents in the American patent database. There are a considerable number of AMPs that exhibit excellent antimicrobial activity against endodontic microbiota at a small inhibitory concentration and modulate an exacerbated immune response, down-regulating bone resorption. All these reasons indicate the antimicrobial peptide-based endodontic treatment as an emerging and promising option. PMID:25447423

  17. Peptide-based Biopolymers in Biomedicine and Biotechnology

    PubMed Central

    Chow, Dominic; Nunalee, Michelle L.; Lim, Dong Woo; Simnick, Andrew J.; Chilkoti, Ashutosh

    2008-01-01

    Peptides are emerging as a new class of biomaterials due to their unique chemical, physical, and biological properties. The development of peptide-based biomaterials is driven by the convergence of protein engineering and macromolecular self-assembly. This review covers the basic principles, applications, and prospects of peptide-based biomaterials. We focus on both chemically synthesized and genetically encoded peptides, including poly-amino acids, elastin-like polypeptides, silk-like polymers and other biopolymers based on repetitive peptide motifs. Applications of these engineered biomolecules in protein purification, controlled drug delivery, tissue engineering, and biosurface engineering are discussed. PMID:19122836

  18. Asthma Outcomes: Exacerbations

    PubMed Central

    Fuhlbrigge, Anne; Peden, David; Apter, Andrea J.; Boushey, Homer A.; Camargo, Carlos; Gern, James; Heymann, Peter W.; Martinez, Fernando D.; Mauger, David; Teague, William G.; Blaisdell, Carol

    2013-01-01

    Background The goals of asthma treatment include preventing recurrent exacerbations. Yet there is no consensus about the terminology for describing or defining “exacerbation,” or about how to characterize an episode’s severity. Objective National Institutes of Health (NIH) institutes and other federal agencies convened an expert group to propose how asthma exacerbation should be assessed as a standardized asthma outcome in future asthma clinical research studies. Methods We utilized comprehensive literature reviews and expert opinion to compile a list of asthma exacerbation outcomes, and classified them as either core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at an NIH-organized workshop in March 2010 and finalized in September 2011. Results No dominant definition of “exacerbation” was found. The most widely used definitions included 3 components, all related to treatment, rather than symptoms: (1) systemic use of corticosteroids, (2) asthma-specific emergency department visits or hospitalization, and (3) use of short-acting β-agonists (SABAs) as quick-relief (sometimes referred to as “rescue” or “reliever”) medications. Conclusions The working group participants propose that the definition of “asthma exacerbation” be “a worsening of asthma requiring the use of systemic corticosteroids to prevent a serious outcome.” As core outcomes, they propose inclusion and separate reporting of several essential variables of an exacerbation. Further, they propose the development of a standardized, component-based definition of “exacerbation” with clear thresholds of severity for each component. PMID:22386508

  19. Targeting dendritic cells in lymph node with an antigen peptide-based nanovaccine for cancer immunotherapy.

    PubMed

    Qian, Yuan; Jin, Honglin; Qiao, Sha; Dai, Yanfeng; Huang, Chuan; Lu, Lisen; Luo, Qingming; Zhang, Zhihong

    2016-08-01

    The design of peptide-based subunit vaccine formulations for the direct delivery of tumor antigen peptides (Aps) to dendritic cells (DCs) localized within draining lymph nodes (DLNs) is challenging. Mature DCs (mDCs) are abundantly distributed within DLNs but have dramatically reduced endocytic uptake and antigen-processing abilities, so their role as potential vaccine targets has been largely overlooked. Here we report an ultra-small biocompatible nanovaccine (α-Ap-FNP) functionalized by avidly targeting delivery of Ap via the scavenger receptor class B1 (SR-B1) pathway to mDCs. The self-assembly, small size (∼30 nm), SR-B1-targeting and optical properties of α-Ap-FNP resulted in its efficient Ap loading, substantial LN accumulation, targeting of mDCs and enhanced Ap presentation, and fluorescence trafficking, respectively. We also demonstrate that the α-Ap-FNP can be either used alone or encapsulated with CpG oligodeoxynucleotide as a prophylactic and therapeutic vaccine. Thus, the excellent properties of α-Ap-FNP provide it potential for clinical applications as a potent nanovaccine for cancer immunotherapy. PMID:27192420

  20. Dark chocolate exacerbates acne.

    PubMed

    Vongraviopap, Saivaree; Asawanonda, Pravit

    2016-05-01

    The effects of chocolate on acne exacerbations have recently been reevaluated. For so many years, it was thought that it had no role in worsening acne. To investigate whether 99% dark chocolate, when consumed in regular daily amounts, would cause acne to worsen in acne-prone male subjects, twenty-five acne prone male subjects were asked to consume 25 g of 99% dark chocolate daily for 4 weeks. Assessments which included Leeds revised acne scores as well as lesion counts took place weekly. Food frequency questionnaire was used, and daily activities were recorded. Statistically significant changes of acne scores and numbers of comedones and inflammatory papules were detected as early as 2 weeks into the study. At 4 weeks, the changes remained statistically significant compared to baseline. Dark chocolate when consumed in normal amounts for 4 weeks can exacerbate acne in male subjects with acne-prone skin. PMID:26711092

  1. Site-Selective Reactions with Peptide-Based Catalysts.

    PubMed

    Giuliano, Michael W; Miller, Scott J

    2016-01-01

    The problem of catalyst-controlled site-selectivity can potentially require a catalyst to overcome energetic barriers larger than those associated with enantioselective reactions. This challenge is a signature of substrates that present reactive sites that are not of equivalent reactivity. Herein we present a narrative of our laboratory's efforts to overcome this challenge using peptide-based catalysts. We highlight the interplay between understanding the inherent reactivity preferences of a given target molecule and the development of catalysts that can overcome intrinsic preferences embedded within a substrate. PMID:26307403

  2. Development of peptide-based patterns by laser transfer

    NASA Astrophysics Data System (ADS)

    Dinca, V.; Kasotakis, E.; Catherine, J.; Mourka, A.; Mitraki, A.; Popescu, A.; Dinescu, M.; Farsari, M.; Fotakis, C.

    2007-12-01

    Peptide-based arrays and patterns have provided a powerful tool in the study of protein recognition and function. A variety of applications have been identified, including the interactions between peptides-enzymes, peptides-proteins, peptides-DNA, peptides-small molecules and peptides-cells. One of the main and most critical unresolved issues is the generation of high-density arrays which maintain the biological function of the peptides. In this study, we employ nanosecond laser-induced forward transfer for the generation of high-density peptide arrays and patterns on modified glass surfaces. We show that peptide-based microarrays can be fabricated on solid surfaces and specifically recognized by appropriate fluorescent tags, with the transfer not affecting the ability of the peptides to form fibrils. These initial results are poised to the construction of larger peptide patterns as scaffolds for the incorporation and display of ligands critical for cell attachment and growth, or for the templating of inorganic materials.

  3. Interferon-alpha/beta deficiency greatly exacerbates arthritogenic disease in mice infected with wild-type chikungunya virus but not with the cell culture-adapted live-attenuated 181/25 vaccine candidate

    PubMed Central

    Gardner, Christina L.; Burke, Crystal W.; Higgs, Stephen T.; Klimstra, William B.; Ryman, Kate D.

    2012-01-01

    In humans, chikungunya virus (CHIKV) infection causes fever, rash, and acute and persisting polyarthalgia/arthritis associated with joint swelling. We report a new CHIKV disease model in adult mice that distinguishes the wild-type CHIKV-LR strain from the live-attenuated vaccine strain (CHIKV-181/25). Although eight-week old normal mice inoculated in the hind footpad developed no hind limb swelling with either virus, CHIKV-LR replicated in musculoskeletal tissues and caused detectable inflammation. In mice deficient in STAT1-dependent interferon (IFN) responses, CHIKV-LR caused significant swelling of the inoculated and contralateral limbs and dramatic inflammatory lesions, while CHIKV-181/25 vaccine and another arthritogenic alphavirus, Sindbis, failed to induce swelling. IFN responses suppressed CHIKV-LR and CHIKV-181/25 replication equally in dendritic cells in vitro whereas macrophages were refractory to infection independently of STAT1-mediated IFN responses. Glycosaminoglycan (GAG) binding may be a CHIKV vaccine attenuation mechanism as CHIKV-LR infectivity was not dependent upon GAG, while CHIKV-181/25 was highly dependent. PMID:22305131

  4. Peptide-based carbon nanotubes for mitochondrial targeting.

    PubMed

    Battigelli, Alessia; Russier, Julie; Venturelli, Enrica; Fabbro, Chiara; Petronilli, Valeria; Bernardi, Paolo; Da Ros, Tatiana; Prato, Maurizio; Bianco, Alberto

    2013-10-01

    In the present study, we report the design and synthesis of peptide-based-multi-walled carbon nanotubes (MWCNTs) to target mitochondria. Targeting these intracellular organelles might open the way to develop alternative systems to address diseases related to genetic mutations in mitochondrial (mt)-DNA, by delivering therapeutic oligonucleotides. The first step towards mitochondrial delivery of this type of nucleic acid was to target MWCNTs to mitochondria by covalent functionalization with a well-known endogenous mitochondrial targeting sequence (MTS). The subcellular localization of the conjugates, which were fluorescently labeled, in murine RAW 264.7 macrophages and human HeLa cells was then studied using different microscopy techniques, such as wide-field epifluorescence microscopy, confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM). The localization of the MTS-MWCNT conjugates into mitochondria was further confirmed by analyzing the isolated organelles using TEM. PMID:23903095

  5. Inhaled protein/peptide-based therapies for respiratory disease.

    PubMed

    Fellner, Robert C; Terryah, Shawn T; Tarran, Robert

    2016-12-01

    Asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) are all chronic pulmonary diseases, albeit with different etiologies, that are characterized by airflow limitation, chronic inflammation, and abnormal mucus production/rheology. Small synthetic molecule-based therapies are commonly prescribed for all three diseases. However, there has been increased interest in "biologicals" to treat these diseases. Biologicals typically constitute protein- or peptide-based therapies and are often more potent than small molecule-based drugs. In this review, we shall describe the pros and cons of several different biological-based therapies for respiratory disease, including dornase alfa, a recombinant DNAase that reduces mucus viscosity and short palate lung and nasal epithelial clone 1 (SPLUNC1)-derived peptides that treat Na(+) hyperabsorption and rebalance CF airway surface liquid homeostasis. PMID:27098663

  6. Peptide-based carbon nanotubes for mitochondrial targeting

    NASA Astrophysics Data System (ADS)

    Battigelli, Alessia; Russier, Julie; Venturelli, Enrica; Fabbro, Chiara; Petronilli, Valeria; Bernardi, Paolo; da Ros, Tatiana; Prato, Maurizio; Bianco, Alberto

    2013-09-01

    In the present study, we report the design and synthesis of peptide-based-multi-walled carbon nanotubes (MWCNTs) to target mitochondria. Targeting these intracellular organelles might open the way to develop alternative systems to address diseases related to genetic mutations in mitochondrial (mt)-DNA, by delivering therapeutic oligonucleotides. The first step towards mitochondrial delivery of this type of nucleic acid was to target MWCNTs to mitochondria by covalent functionalization with a well-known endogenous mitochondrial targeting sequence (MTS). The subcellular localization of the conjugates, which were fluorescently labeled, in murine RAW 264.7 macrophages and human HeLa cells was then studied using different microscopy techniques, such as wide-field epifluorescence microscopy, confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM). The localization of the MTS-MWCNT conjugates into mitochondria was further confirmed by analyzing the isolated organelles using TEM.In the present study, we report the design and synthesis of peptide-based-multi-walled carbon nanotubes (MWCNTs) to target mitochondria. Targeting these intracellular organelles might open the way to develop alternative systems to address diseases related to genetic mutations in mitochondrial (mt)-DNA, by delivering therapeutic oligonucleotides. The first step towards mitochondrial delivery of this type of nucleic acid was to target MWCNTs to mitochondria by covalent functionalization with a well-known endogenous mitochondrial targeting sequence (MTS). The subcellular localization of the conjugates, which were fluorescently labeled, in murine RAW 264.7 macrophages and human HeLa cells was then studied using different microscopy techniques, such as wide-field epifluorescence microscopy, confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM). The localization of the MTS-MWCNT conjugates into mitochondria was further confirmed by analyzing the

  7. Modular Design of Self-Assembling Peptide-Based Nanotubes.

    PubMed

    Burgess, Natasha C; Sharp, Thomas H; Thomas, Franziska; Wood, Christopher W; Thomson, Andrew R; Zaccai, Nathan R; Brady, R Leo; Serpell, Louise C; Woolfson, Derek N

    2015-08-26

    An ability to design peptide-based nanotubes (PNTs) rationally with defined and mutable internal channels would advance understanding of peptide self-assembly, and present new biomaterials for nanotechnology and medicine. PNTs have been made from Fmoc dipeptides, cyclic peptides, and lock-washer helical bundles. Here we show that blunt-ended α-helical barrels, that is, preassembled bundles of α-helices with central channels, can be used as building blocks for PNTs. This approach is general and systematic, and uses a set of de novo helical bundles as standards. One of these bundles, a hexameric α-helical barrel, assembles into highly ordered PNTs, for which we have determined a structure by combining cryo-transmission electron microscopy, X-ray fiber diffraction, and model building. The structure reveals that the overall symmetry of the peptide module plays a critical role in ripening and ordering of the supramolecular assembly. PNTs based on pentameric, hexameric, and heptameric α-helical barrels sequester hydrophobic dye within their lumens. PMID:26219086

  8. Recent Developments in Peptide-Based Nucleic Acid Delivery

    PubMed Central

    Veldhoen, Sandra; Laufer, Sandra D.; Restle, Tobias

    2008-01-01

    Despite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among these synthetic vectors are cationic polymers, branched dendrimers, cationic liposomes and cell-penetrating peptides (CPPs). The latter represent an assortment of fairly unrelated sequences essentially characterised by a high content of basic amino acids and a length of 10–30 residues. CPPs are capable of mediating the cellular uptake of hydrophilic macromolecules like peptides and nucleic acids (e.g. siRNAs, aptamers and antisense-oligonucleotides), which are internalised by cells at a very low rate when applied alone. Up to now, numerous sequences have been reported to show cell-penetrating properties and many of them have been used to successfully transport a variety of different cargos into mammalian cells. In recent years, it has become apparent that endocytosis is a major route of internalisation even though the mechanisms underlying the cellular translocation of CPPs are poorly understood and still subject to controversial discussions. In this review, we will summarise the latest developments in peptide-based cellular delivery of nucleic acid cargos. We will discuss different mechanisms of entry, the intracellular fate of the cargo, correlation studies of uptake versus biological activity of the cargo as well as technical problems and pitfalls. PMID:19325804

  9. Nanoscale dynamics and aging of fibrous peptide-based gels

    SciTech Connect

    Dudukovic, Nikola A.; Zukoski, Charles F.

    2014-10-28

    Solutions of the aromatic dipeptide derivative molecule fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) in dimethyl sulfoxide produce fibrous gels when mixed with water. We study the evolution of density fluctuations of this three-component system using X-ray photon correlation spectroscopy (XPCS) and compare these results to the macroscopic rheology of the gels and optical observations of the microstructure evolution. At the investigated scattering angles, the intensity autocorrelation functions do not follow behavior expected for simple diffusion of individual Fmoc-FF molecules localized within cages of nearest neighbors. Instead, the dynamics are associated with density fluctuations on length scales of ∼10–100 nm arising from disaggregation and reformation of fibers, leading to an increasingly uniform network. This process is correlated with the growth of the elastic modulus, which saturates at long times. Autocorrelation functions and relaxation times acquired from XPCS measurements are consistent with relaxation rates of structures at dynamic equilibrium. This study provides further support to the concept of exploring peptide-based gelators as valence-limited patchy particles capable of forming equilibrium gels.

  10. Nanoscale dynamics and aging of fibrous peptide-based gels.

    PubMed

    Dudukovic, Nikola A; Zukoski, Charles F

    2014-10-28

    Solutions of the aromatic dipeptide derivative molecule fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) in dimethyl sulfoxide produce fibrous gels when mixed with water. We study the evolution of density fluctuations of this three-component system using X-ray photon correlation spectroscopy (XPCS) and compare these results to the macroscopic rheology of the gels and optical observations of the microstructure evolution. At the investigated scattering angles, the intensity autocorrelation functions do not follow behavior expected for simple diffusion of individual Fmoc-FF molecules localized within cages of nearest neighbors. Instead, the dynamics are associated with density fluctuations on length scales of ~10-100 nm arising from disaggregation and reformation of fibers, leading to an increasingly uniform network. This process is correlated with the growth of the elastic modulus, which saturates at long times. Autocorrelation functions and relaxation times acquired from XPCS measurements are consistent with relaxation rates of structures at dynamic equilibrium. This study provides further support to the concept of exploring peptide-based gelators as valence-limited patchy particles capable of forming equilibrium gels. PMID:25362339

  11. Nanoscale dynamics and aging of fibrous peptide-based gels

    NASA Astrophysics Data System (ADS)

    Dudukovic, Nikola A.; Zukoski, Charles F.

    2014-10-01

    Solutions of the aromatic dipeptide derivative molecule fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) in dimethyl sulfoxide produce fibrous gels when mixed with water. We study the evolution of density fluctuations of this three-component system using X-ray photon correlation spectroscopy (XPCS) and compare these results to the macroscopic rheology of the gels and optical observations of the microstructure evolution. At the investigated scattering angles, the intensity autocorrelation functions do not follow behavior expected for simple diffusion of individual Fmoc-FF molecules localized within cages of nearest neighbors. Instead, the dynamics are associated with density fluctuations on length scales of ˜10-100 nm arising from disaggregation and reformation of fibers, leading to an increasingly uniform network. This process is correlated with the growth of the elastic modulus, which saturates at long times. Autocorrelation functions and relaxation times acquired from XPCS measurements are consistent with relaxation rates of structures at dynamic equilibrium. This study provides further support to the concept of exploring peptide-based gelators as valence-limited patchy particles capable of forming equilibrium gels.

  12. Recent developments in peptide-based nucleic acid delivery.

    PubMed

    Veldhoen, Sandra; Laufer, Sandra D; Restle, Tobias

    2008-06-01

    Despite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among these synthetic vectors are cationic polymers, branched dendrimers, cationic liposomes and cell-penetrating peptides (CPPs). The latter represent an assortment of fairly unrelated sequences essentially characterised by a high content of basic amino acids and a length of 10-30 residues. CPPs are capable of mediating the cellular uptake of hydrophilic macromolecules like peptides and nucleic acids (e.g. siRNAs, aptamers and antisense-oligonucleotides), which are internalised by cells at a very low rate when applied alone. Up to now, numerous sequences have been reported to show cell-penetrating properties and many of them have been used to successfully transport a variety of different cargos into mammalian cells. In recent years, it has become apparent that endocytosis is a major route of internalisation even though the mechanisms underlying the cellular translocation of CPPs are poorly understood and still subject to controversial discussions. In this review, we will summarise the latest developments in peptide-based cellular delivery of nucleic acid cargos. We will discuss different mechanisms of entry, the intracellular fate of the cargo, correlation studies of uptake versus biological activity of the cargo as well as technical problems and pitfalls. PMID:19325804

  13. A peptide-based fluorescent chemosensor for multianalyte detection.

    PubMed

    Wang, Peng; Liu, Lixuan; Zhou, Panpan; Wu, Wenyu; Wu, Jiang; Liu, Weisheng; Tang, Yu

    2015-10-15

    A novel multifunctional peptide fluorescent chemosensor (DP-3) with a lysine backbone and double sides conjugated with histidine and dansyl groups has been designed and synthesized by solid phase synthesis. This chemosensor is a promising analytical tool for detecting Zn(2+), Cu(2+), and S(2-) based on different mechanisms in 100% aqueous solutions, and intracellular biosensing has been successfully actualized. The peptide beacon structure of DP-3 makes it more stable and capable of achieving multianalyte detection, especially for sulfide ions. Until now, there have been few examples of using a peptide fluorescent chemosensor to detect anions with a continuous method. As designed, DP-3 exhibits excellent cell permeation and low biotoxicity and displays high selectivity and sensitivity, with Zn(2+) and Cu(2+) detection limits of 82 nM and 78 nM, respectively. This study raises the new possibility of a highly selective peptide fluorescent chemosensor for multifunctional detection, including cation and anions, by different mechanisms in environmental and biological systems. We expect that this work will inspire the development of a multifunctional beacon peptide-based fluorescent chemosensor library using modifiable lateral and terminal groups for a variety of practical applications in physiological and pathological events. PMID:25957834

  14. Aspirin-exacerbated cutaneous disease.

    PubMed

    Sánchez-Borges, Mario; Caballero-Fonseca, Fernan; Capriles-Hulett, Arnaldo

    2013-05-01

    It has been recognized that a high proportion of chronic urticaria patients experience symptom aggravation when exposed to aspirin and NSAIDs. This clinical picture is known as Aspirin-exacerbated cutaneous disease. The pathogenesis of these exacerbations is related to the inhibition of cyclooxygenase-1 leading to a decreased synthesis of PGE2 and an increased cysteinyl leukotriene production in the skin and subcutaneous tissues. Patient management comprises the treatment of the underlying cutaneous disease with nonsedating antihistamines and other medications, avoidance of COX-1 inhibitors, and the use of alternative NSAIDs that do not inhibit COX-1 for the relief of pain, inflammation and fever. PMID:23639712

  15. Conundrum in an asthma exacerbation.

    PubMed

    Isaac, Barney Thomas Jesudason; McLellan, Thomas; Samuel, Johnson; Yung, Bernard

    2016-01-01

    A 66-year-old man, an asthmatic, presented with symptoms suggestive of an acute exacerbation of asthma. His arterial blood gas revealed type 1 respiratory failure (PaO2 <8 kPa or 60 mm Hg with normal or low PaCO2) with a compensated lactic acidosis. He was treated for an asthma exacerbation and sepsis. Despite treatment, his respiratory rate remained elevated although his hypoxaemia improved. There was progressive worsening of the lactic acidosis. Treatment for sepsis was augmented. Peak flow measurements were not used to assess the severity of his exacerbation nor his response to treatment. An alternate diagnosis of acute coronary syndrome with acute pulmonary oedema was made and his asthma treatment was stopped. This coincided with a decline in his serum lactate. A diagnosis of salbutamol-induced lactic acidosis (SILA) was made. SILA is a relatively common complication of salbutamol therapy in moderate/severe asthma exacerbations. It is caused by a mechanism different from the lactataemia that is associated with septic shock and life-threatening asthma. PMID:27166007

  16. Hypersensitivity and vaccines: an update.

    PubMed

    Barbaud, Annick; Deschildre, Antoine; Waton, Julie; Raison-Peyron, Nadia; Tréchot, Philippe

    2013-04-01

    Allergic reactions to vaccines can be classified as sensitivity to one of the vaccine components, pseudo-allergic reactions, often after hyperimmunization, and exacerbation of atopic symptoms or vasculitis. Pseudo-allergic reactions, some possibly due to hyperimmunization, are probably more common than true allergies. Atopic reactions should not be confused with the "flash" phenomenon, defined as an exacerbation of an allergic reaction due to a reduction in the allergic reactivity threshold following the vaccine injection. BCGitis occurs frequently, and for this reason, guidelines for Bacillus Calmette-Guérin (BCG) have been modified. The vaccine is now reserved for people at risk of exposure to Mycobacterium tuberculosis. This review provides an update on the vaccination modalities for people allergic to eggs, on the assessment that should be performed when a reaction occurs due to tetanus vaccination, on the urticaria after hepatitis vaccination, on an aluminum granuloma, which is more and more frequent in young children, and vasculitis after flu vaccination and BCGitis. The side effects associated with new, recently released vaccines, such as anti-influenza A H1N1 or anti-human papilloma virus (HPV) will also be presented. PMID:23238161

  17. Status of Contraceptive Vaccines

    PubMed Central

    Naz, Rajesh K.

    2008-01-01

    Problem This is a review of antisperm contraceptive vaccines (CV), and synthesis of human scFv antibodies that can be used as immunocontraceptives. Method of study Various methods of proteomics and genomics, peptide synthesis, phage display technology, and antibody engineering were used to obtain multi-epitope vaccines and human scFv antibodies from immunoinfertile and vasectomized men. The present review primarily focuses on the effect of multi-epitope vaccines and Izumo on fertility and synthesis and characterization of sperm specific human scFv antibodies. Results The immunization with Izumo peptides causes a contraceptive effect in female mice. The efficacy is enhanced by combination vaccination, including peptides based on other sperm antigens. Using phage display technology, we were able to synthesize at least four novel scFv antibodies with unique complimentarity determining regions (CDRs) that reacted with specific fertility-related sperm antigens. These antibodies inhibited human sperm function in vitro, and their immunocontraceptive effect in vivo is currently being investigated. Conclusions The multi-epitope vaccines may provide an efficacious and viable approach to contraception. The human scFv antibodies, if they block fertility in vivo, may provide unique and novel immunocontraceptives, the first of its kind for human use. The multi-epitope CV and preformed engineered antibodies of defined specificity may obliterate the concern related to inter-individual variability of the immune response. PMID:19086987

  18. Designing the mechanical properties of peptide-based supramolecular hydrogels for biomedical applications

    NASA Astrophysics Data System (ADS)

    Li, Ying; Qin, Meng; Cao, Yi; Wang, Wei

    2014-05-01

    Hydrogels are a class of special materials that contain a large amount of water and behave like rubber. These materials have found broad applications in tissue engineering, cell culturing, regenerative medicine etc. Recently, the exploration of peptide-based supramolecular hydrogels has greatly expanded the repertoire of hydrogels suitable for biomedical applications. However, the mechanical properties of peptide-based hydrogels are intrinsically weak. Therefore, it is crucial to develop methods that can improve the mechanical stability of such peptide-based hydrogels. In this review, we explore the factors that determine or influence the mechanical stability of peptide-based hydrogels and summarize several key elements that may guide scientists to achieve mechanically improved hydrogels. In addition, we exemplified several methods that have been successfully developed to prepare hydrogels with enhanced mechanical stability. These mechanically strong peptide-based hydrogels may find broad applications as novel biomaterials. It is still challenging to engineer hydrogels in order to mimic the mechanical properties of biological tissues. More hydrogel materials with optimal mechanical properties suitable for various types of biological applications will be available in the near future.

  19. Mucosal Pre-Exposure to Th17-Inducing Adjuvants Exacerbates Pathology after Influenza Infection

    PubMed Central

    Gopal, Radha; Rangel-Moreno, Javier; Fallert Junecko, Beth A.; Mallon, Daniel J.; Chen, Kong; Pociask, Derek A.; Connell, Terry D.; Reinhart, Todd A.; Alcorn, John F.; Ross, Ted M.; Kolls, Jay K.; Khader, Shabaana A.

    2015-01-01

    Mucosal vaccines are thought to confer superior protection against mucosal infectious diseases. In addition, mucosal routes of vaccine delivery preferentially induce the generation of T helper 17 (Th17) cells, which produce the cytokine IL-17. Th17 cells are critical in mediating vaccine-induced immunity against several mucosal infectious diseases. However, IL-17 is also a potent proinflammatory cytokine, and we recently showed that IL-17 mediates immunopathology and lung injury after influenza infection in mice. In the present study, we tested the hypothesis that mucosal pre-exposure to Th17-inducing adjuvants can promote disease exacerbation upon subsequent infection with influenza virus. Mice mucosally pre-exposed to Th17-inducing adjuvants, such as type II heat-labile enterotoxin or cholera toxin, resulted in increased morbidity and exacerbated lung inflammation upon subsequent infection with influenza virus. Furthermore, the increased morbidity was accompanied by increased expression of inflammatory chemokines and increased accumulation of neutrophils. Importantly, blockade of the IL-17 pathway in mice pre-exposed to Th17-inducing adjuvants resulted in attenuation of the inflammatory phenotype seen in influenza-infected mice. Our findings indicate that, before mucosal Th17-inducing adjuvants can be used in vaccine strategies, the short- and long-term detrimental effects of such adjuvants on disease exacerbation and lung injury in response to infections, such as influenza, should be carefully studied. PMID:24183780

  20. Infective Exacerbation of Pasteurella multocida

    PubMed Central

    Hamada, Mayumi; Elshimy, Noha; Abusriwil, Hatem

    2016-01-01

    An 89-year-old lady presented with a one-day history of shortness of breath as well as a cough productive of brown sputum. Her medical history was significant for chronic obstructive pulmonary disease (COPD). She was in severe type one respiratory failure and blood tests revealed markedly raised inflammatory markers; however her chest X-ray was clear. On examination there was bronchial breathing with widespread crepitations and wheeze. She was treated as per an infective exacerbation of COPD. Subsequent blood cultures grew Pasteurella multocida, a common commensal in the oropharynx of domesticated animals. The patient was then asked about any contact with animals, after which she revealed she had a dog and was bitten on her left hand the day before admission. We should not forget to enquire about recent history of injuries or animal bites when patients present acutely unwell. She made a complete recovery after treatment with penicillin. PMID:26942025

  1. Infective Exacerbation of Pasteurella multocida.

    PubMed

    Hamada, Mayumi; Elshimy, Noha; Abusriwil, Hatem

    2016-01-01

    An 89-year-old lady presented with a one-day history of shortness of breath as well as a cough productive of brown sputum. Her medical history was significant for chronic obstructive pulmonary disease (COPD). She was in severe type one respiratory failure and blood tests revealed markedly raised inflammatory markers; however her chest X-ray was clear. On examination there was bronchial breathing with widespread crepitations and wheeze. She was treated as per an infective exacerbation of COPD. Subsequent blood cultures grew Pasteurella multocida, a common commensal in the oropharynx of domesticated animals. The patient was then asked about any contact with animals, after which she revealed she had a dog and was bitten on her left hand the day before admission. We should not forget to enquire about recent history of injuries or animal bites when patients present acutely unwell. She made a complete recovery after treatment with penicillin. PMID:26942025

  2. Polio Vaccination

    MedlinePlus

    ... inactive polio vaccine OPV=oral polio vaccine Polio Vaccination Pronounced [PO-lee-oh] Recommend on Facebook Tweet ... handling and storage Related Pages Global Vaccines and Immunization Global Polio Also Known As & Abbreviations Polio=poliomyelitis ...

  3. Chemical Platforms for Peptide Vaccine Constructs.

    PubMed

    Ramesh, Suhas; Cherkupally, Prabhakar; Govender, Thavendran; Kruger, Hendrik G; Albericio, Fernando; de la Torre, Beatriz G

    2015-01-01

    Knowledge of the sequences and structures of proteins from pathogenic microorganisms has been put to great use in the field of protein chemistry for the development of peptide-based vaccines. These vaccine constructs include chemically tailored, shorter peptidic fragments that can induce high immunogenicity, thus shunning the allergenic and nonimmunogenic part of the antigens. Based on this concept, several different chemistries have been pursued to obtain novel platforms onto which antigenic epitopes can be tethered, with the aim to achieve a higher antibody response. In this regard, here we attempt to summarize the chemical strategies developed for the presentation of peptide epitopes. PMID:26067818

  4. Vaccine hesitancy

    PubMed Central

    Dubé, Eve; Laberge, Caroline; Guay, Maryse; Bramadat, Paul; Roy, Réal; Bettinger, Julie A.

    2013-01-01

    Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and an increasing risk of vaccine-preventable disease outbreaks and epidemics. This review provides an overview of the phenomenon of vaccine hesitancy. First, we will characterize vaccine hesitancy and suggest the possible causes of the apparent increase in vaccine hesitancy in the developed world. Then we will look at determinants of individual decision-making about vaccination. PMID:23584253

  5. A rare case of ulcerative colitis exacerbated by VZV infection.

    PubMed

    Nishimura, Satoshi; Yoshino, Takuya; Fujikawa, Yoshiki; Watanabe, Masaki; Yazumi, Shujiro

    2015-12-01

    A 16-years old man with severe ulcerative colitis (UC) was admitted to our hospital. After initiating treatment with corticosteroid for UC, chicken pox appeared. At the same time of appearance of chicken pox, the disease activity of UC was exacerbated. After initiating the treatment with acyclovir, both chicken pox and UC improved. Because colonoscopic findings revealed the remaining of moderately active UC, initiating the treatment with infliximab could induce clinical remission of UC without relapse of varicella-zoster virus (VZV) infection. This is a very rare case of UC with concomitant VZV infection. According to our report, the vaccination for VZV prior to immunosuppressive treatments would be necessary for VZV naïve patients with UC. PMID:26552918

  6. Vaccine Safety

    MedlinePlus

    ... During Pregnancy Frequently Asked Questions about Vaccine Recalls Historical Vaccine Safety Concerns FAQs about GBS and Menactra ... CISA Resources for Healthcare Professionals Evaluation Current Studies Historical Background 2001-12 Publications Technical Reports Vaccine Safety ...

  7. Smallpox Vaccination

    MedlinePlus

    ... Newsletters Events Also Known As Smallpox = Vaccinia Smallpox Vaccination Recommend on Facebook Tweet Share Compartir The smallpox ... like many other vaccines. For that reason, the vaccination site must be cared for carefully to prevent ...

  8. HPV vaccine

    MedlinePlus

    Vaccine - HPV; Immunization - HPV; Gardasil; Cervarix; HPV2; HPV4; Vaccine to prevent cervical cancer ... and Gynecologists. Committee Opinion No. 588: Human Papillomavirus Vaccination. Obstet Gynecol . 2014;123(3):712-8. PMID: ...

  9. Do females behave differently in COPD exacerbation?

    PubMed Central

    Kilic, Hatice; Kokturk, Nurdan; Sari, Gulcin; Cakır, Mustafa

    2015-01-01

    Introduction Little is known about whether there is any sex effect on chronic obstructive lung disease (COPD) exacerbations. This study is intended to describe the possible sex-associated differences in exacerbation profile in COPD patients. Methods A total of 384 COPD patients who were hospitalized due to exacerbation were evaluated retrospectively for their demographics and previous and current exacerbation characteristics. Results The study was conducted on 109 (28%) female patients and 275 (72%) male patients. The mean age was 68.30±10.46 years. Although females had better forced expiratory volume in 1 second and near-normal forced vital capacity, they had much impaired arterial blood gas levels (partial oxygen pressure [PO2] was 36.28 mmHg vs 57.93 mmHg; partial carbon dioxide pressure [PCO2] was 45.97 mmHg vs 42.49 mmHg; P=0.001), indicating severe exacerbation with respiratory failure. More females had two exacerbations and two hospitalizations, while more men had one exacerbation and one hospitalization. Low adherence to treatment and pulmonary embolism were more frequent in females. Females had longer time from the onset of symptoms till the admission and longer hospitalization duration than males. Comorbidities were less in number and different in women (P<0.05). Women were undertreated and using more oral corticosteroids. Conclusion Current data showed that female COPD patients might be more prone to have severe exacerbations, a higher number of hospitalizations, and prolonged length of stay for hospitalization. They have a different comorbidity profile and might be undertreated for COPD. PMID:25977604

  10. 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

  11. Incidence of pulmonary embolism during COPD exacerbation*, **

    PubMed Central

    Akpinar, Evrim Eylem; Hoşgün, Derya; Akpýnar, Serdar; Ataç, Gökçe Kaan; Doğanay, Beyza; Gülhan, Meral

    2014-01-01

    OBJECTIVE: Because pulmonary embolism (PE) and COPD exacerbation have similar presentations and symptoms, PE can be overlooked in COPD patients. Our objective was to determine the prevalence of PE during COPD exacerbation and to describe the clinical aspects in COPD patients diagnosed with PE. METHODS: This was a prospective study conducted at a university hospital in the city of Ankara, Turkey. We included all COPD patients who were hospitalized due to acute exacerbation of COPD between May of 2011 and May of 2013. All patients underwent clinical risk assessment, arterial blood gas analysis, chest CT angiography, and Doppler ultrasonography of the lower extremities. In addition, we measured D-dimer levels and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels. RESULTS: We included 172 patients with COPD. The prevalence of PE was 29.1%. The patients with pleuritic chest pain, lower limb asymmetry, and high NT-pro-BNP levels were more likely to develop PE, as were those who were obese or immobile. Obesity and lower limb asymmetry were independent predictors of PE during COPD exacerbation (OR = 4.97; 95% CI, 1.775-13.931 and OR = 2.329; 95% CI, 1.127-7.105, respectively). CONCLUSIONS: The prevalence of PE in patients with COPD exacerbation was higher than expected. The association between PE and COPD exacerbation should be considered, especially in patients who are immobile or obese. PMID:24626268

  12. Towards a peptide-based suspension array for the detection of pestivirus antibodies in swine.

    PubMed

    van der Wal, Fimme J; Jelsma, Tinka; Fijten, Helmi; Achterberg, René P; Loeffen, Willie L A

    2016-09-01

    Classical swine fever (CSF) is a highly contagious and lethal disease in swine. Serological tests for the diagnosis of CSF need not only to detect antibodies against CSFV, but also need to differentiate these from antibodies against other pestiviruses. To investigate the possibilities of specific peptide-based serology, various synthetic peptides that represent a well-described linear epitope of the CSFV E2 protein (TAVSPTTLR) were used to test the viability of a peptide-based suspension array for the detection of antibodies against pestiviruses in swine. The results show that N-terminally biotinylated peptides can bind to avidin conjugated beads, and function in detection of the corresponding monoclonal antibody WH303. There are indications that the length of the spacer between epitope and biotin affect the efficiency of the peptide-antibody interaction. A protocol was established that enables probing for antibodies in porcine sera, where neutravidin-blocking of serum and the use of empty control beads for normalization was crucial. With a set of porcine sera with antibodies against various pestiviruses, the proof of concept of a peptide-based suspension array for specific detection of antibodies against pestiviruses in porcine sera was demonstrated. PMID:27166561

  13. [Vaccination perspectives].

    PubMed

    Saliou, P; Plotkin, S

    1994-01-01

    The aim of vaccinology is to improve the available vaccines and to develop new ones in the light of progress in immunology, molecular biology and biotechnologies. But it must go beyond this, and aim to protect all populations and control diseases, even eradicate them where possible. New vaccine strategies must be developed taking into account the epidemiology of diseases and the inherent logistic problems of implementing these strategies under local conditions. There are three major thrusts to the progress of the discipline. The improvement of the vaccines available. One of the drives of vaccinology is not only to deliver vaccines of increasing safety (replacement of the current vaccine for whooping cough with an acellular vaccine for example), but also to improve vaccine efficacy and immunogenicity (in particular for flu, tuberculosis, cholera and rabies vaccines). The optimisation of vaccination programmes and strategies for vaccinations. The ideal is to protect against the greatest possible number of diseases with the smallest number of vaccinations. The development of combinations of vaccines is central to this goal. The objective for the year 2000 is a hexavalent vaccine DTPP Hib HB. The development of new vaccines. Classic techniques continue to be successfully used (inactivated hepatitis A vaccine; attenuated live vaccines for chicken pox and dengue fever; conjugated polyosidic bacterial vaccines for meningococci and Streptococcus pneumoniae). However, it will become possible to prepare vaccines against most transmissible diseases using genetic engineering techniques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7921696

  14. Vaccine Hesitancy.

    PubMed

    Jacobson, Robert M; St Sauver, Jennifer L; Finney Rutten, Lila J

    2015-11-01

    Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact. PMID:26541249

  15. Predicting asthma exacerbations employing remotely monitored adherence.

    PubMed

    Killane, Isabelle; Sulaiman, Imran; MacHale, Elaine; Breathnach, Aoife; Taylor, Terence E; Holmes, Martin S; Reilly, Richard B; Costello, Richard W

    2016-03-01

    This Letter investigated the efficacy of a decision-support system, designed for respiratory medicine, at predicting asthma exacerbations in a multi-site longitudinal randomised control trial. Adherence to inhaler medication was acquired over 3 months from patients with asthma employing a dose counter and a remote monitoring adherence device which recorded participant's inhaler use: n = 184 (23,656 audio files), 61% women, age (mean ± sd) 49.3 ± 16.4. Data on occurrence of exacerbations was collected at three clinical visits, 1 month apart. The relative risk of an asthma exacerbation for those with good and poor adherence was examined employing a univariate and multivariate modified Poisson regression approach; adjusting for age, gender and body mass index. For all months dose counter adherence was significantly (p < 0.01) higher than remote monitoring adherence. Overall, those with poor adherence had a 1.38 ± 0.34 and 1.42 ± 0.39 (remotely monitored) and 1.25 ± 0.32 and 1.18 ± 0.31 (dose counter) higher relative risk of an exacerbation in model 1 and model 2, respectively. However, this was not found to be statistically significantly different. Remotely monitored adherence holds important clinical information and future research should focus on refining adherence and exacerbation measures. Decision-support systems based on remote monitoring may enhance patient-physician communication, possibly reducing preventable adverse events. PMID:27222733

  16. Acute Exacerbations of Idiopathic Pulmonary Fibrosis

    PubMed Central

    Collard, Harold R.; Moore, Bethany B.; Flaherty, Kevin R.; Brown, Kevin K.; Kaner, Robert J.; King, Talmadge E.; Lasky, Joseph A.; Loyd, James E.; Noth, Imre; Olman, Mitchell A.; Raghu, Ganesh; Roman, Jesse; Ryu, Jay H.; Zisman, David A.; Hunninghake, Gary W.; Colby, Thomas V.; Egan, Jim J.; Hansell, David M.; Johkoh, Takeshi; Kaminski, Naftali; Kim, Dong Soon; Kondoh, Yasuhiro; Lynch, David A.; Müller-Quernheim, Joachim; Myers, Jeffrey L.; Nicholson, Andrew G.; Selman, Moisés; Toews, Galen B.; Wells, Athol U.; Martinez, Fernando J.

    2007-01-01

    The natural history of idiopathic pulmonary fibrosis (IPF) has been characterized as a steady, predictable decline in lung function over time. Recent evidence suggests that some patients may experience a more precipitous course, with periods of relative stability followed by acute deteriorations in respiratory status. Many of these acute deteriorations are of unknown etiology and have been termed acute exacerbations of IPF. This perspective is the result of an international effort to summarize the current state of knowledge regarding acute exacerbations of IPF. Acute exacerbations of IPF are defined as acute, clinically significant deteriorations of unidentifiable cause in patients with underlying IPF. Proposed diagnostic criteria include subjective worsening over 30 days or less, new bilateral radiographic opacities, and the absence of infection or another identifiable etiology. The potential pathobiological roles of infection, disordered cell biology, coagulation, and genetics are discussed, and future research directions are proposed. PMID:17585107

  17. Azithromycin for Prevention of Exacerbations of COPD

    PubMed Central

    Albert, Richard K.; Connett, John; Bailey, William C.; Casaburi, Richard; Cooper, J. Allen D.; Criner, Gerard J.; Curtis, Jeffrey L.; Dransfield, Mark T.; Han, MeiLan K.; Lazarus, Stephen C.; Make, Barry; Marchetti, Nathaniel; Martinez, Fernando J.; Madinger, Nancy E.; McEvoy, Charlene; Niewoehner, Dennis E.; Porsasz, Janos; Price, Connie S.; Reilly, John; Scanlon, Paul D.; Sciurba, Frank C.; Scharf, Steven M.; Washko, George R.; Woodruff, Prescott G.; Anthonisen, Nicholas R.

    2011-01-01

    BACKGROUND Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases. METHODS We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval. RESULTS A total of 1577 subjects were screened; 1142 (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily (570 participants), or placebo (572 participants) for 1 year in addition to their usual care. The rate of 1-year follow-up was 89% in the azithromycin group and 90% in the placebo group. The median time to the first exacerbation was 266 days (95% confidence interval [CI], 227 to 313) among participants receiving azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants receiving placebo (P<0.001). The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P=0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P<0.001). The scores on the St. George’s Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [±SD] decrease of 2.8±12.8 vs. 0.6±11.4, P=0.004); the percentage of participants with more than the minimal clinically important difference of −4 units was 43% in the azithromycin group, as compared with 36% in the placebo group (P=0.03). Hearing decrements were more common in the azithromycin group than in the placebo group (25% vs. 20%, P=0.04). CONCLUSIONS Among selected subjects with COPD, azithromycin taken daily for

  18. Rheological properties of peptide-based hydrogels for biomedical and other applications†

    PubMed Central

    Yan, Congqi; Pochan, Darrin J.

    2011-01-01

    Peptide-based hydrogels are an important class of biomaterials finding use in food industry and potential use in tissue engineering, drug delivery and microfluidics. A primary experimental method to explore the physical properties of these hydrogels is rheology. A fundamental understanding of peptide hydrogel mechanical properties and underlying molecular mechanisms is crucial for determining whether these biomaterials are potentially suitable for biotechnological uses. In this critical review, we cover the literature containing rheological characterization of the physical properties of peptide and polypeptide-based hydrogels including hydrogel bulk mechanical properties, gelation mechanisms, and the behavior of hydrogels during and after flow. PMID:20422104

  19. Development of a peptide-based inducer of nuclear receptors degradation.

    PubMed

    Demizu, Yosuke; Ohoka, Nobumichi; Nagakubo, Takaya; Yamashita, Hiroko; Misawa, Takashi; Okuhira, Keiichiro; Naito, Mikihiko; Kurihara, Masaaki

    2016-06-01

    A peptide-based protein knockdown system for inducing nuclear receptors degradation via the ubiquitin-proteasome system was developed. Specifically, the designed molecules were composed of two biologically active scaffolds: a peptide that binds to the estrogen receptor α (ERα) surface and an MV1 molecule that binds to cellular inhibitors of apoptosis proteins (IAP: cIAP1/cIAP2/XIAP) to induce ubiquitylation of the ERα. The hybrid peptides induced IAP-mediated ubiquitylation followed by proteasomal degradation of the ERα. Those peptides were also applicable for inducing androgen receptor (AR) degradation. PMID:27086122

  20. Lung microbiome dynamics in COPD exacerbations.

    PubMed

    Wang, Zhang; Bafadhel, Mona; Haldar, Koirobi; Spivak, Aaron; Mayhew, David; Miller, Bruce E; Tal-Singer, Ruth; Johnston, Sebastian L; Ramsheh, Mohammadali Yavari; Barer, Michael R; Brightling, Christopher E; Brown, James R

    2016-04-01

    Increasing evidence suggests that the lung microbiome plays an important role in chronic obstructive pulmonary disease (COPD) severity. However, the dynamics of the lung microbiome during COPD exacerbations and its potential role in disease aetiology remain poorly understood.We completed a longitudinal 16S ribosomal RNA survey of the lung microbiome on 476 sputum samples collected from 87 subjects with COPD at four visits defined as stable state, exacerbation, 2 weeks post-therapy and 6 weeks recovery.Our analysis revealed a dynamic lung microbiota where changes appeared to be associated with exacerbation events and indicative of specific exacerbation phenotypes. Antibiotic and steroid treatments appear to have differential effects on the lung microbiome. We depict a microbial interaction network for the lung microbiome and suggest that perturbation of a few bacterial operational taxonomic units, in particularHaemophilusspp., could greatly impact the overall microbial community structure. Furthermore, several serum and sputum biomarkers, in particular sputum interleukin-8, appear to be highly correlated with the structure and diversity of the microbiome.Our study furthers the understanding of lung microbiome dynamics in COPD patients and highlights its potential as a biomarker, and possibly a target, for future respiratory therapeutics. PMID:26917613

  1. Prevention of Acute Exacerbations of COPD

    PubMed Central

    Bourbeau, Jean; Diekemper, Rebecca L.; Ouellette, Daniel R.; Goodridge, Donna; Hernandez, Paul; Curren, Kristen; Balter, Meyer S.; Bhutani, Mohit; Camp, Pat G.; Celli, Bartolome R.; Dechman, Gail; Dransfield, Mark T.; Fiel, Stanley B.; Foreman, Marilyn G.; Hanania, Nicola A.; Ireland, Belinda K.; Marchetti, Nathaniel; Marciniuk, Darcy D.; Mularski, Richard A.; Ornelas, Joseph; Stickland, Michael K.

    2015-01-01

    BACKGROUND: COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations. METHODS: In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion. RESULTS: The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in

  2. COPD exacerbations by disease severity in England

    PubMed Central

    Merinopoulou, Evie; Raluy-Callado, Mireia; Ramagopalan, Sreeram; MacLachlan, Sharon; Khalid, Javaria Mona

    2016-01-01

    Objectives Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated disease progression and are important drivers of health care resource utilization. The study aimed to quantify the rates of COPD exacerbations in England and assess health care resource utilization by severity categories according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013. Methods Data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics were used to identify patients with a COPD diagnosis aged ≥40 years. Those with complete spirometric, modified Medical Research Council Dyspnea Scale information, and exacerbation history 12 months prior to January 1, 2011 (index date) were classified into GOLD severity groups. Study outcomes over follow-up (up to December 31, 2013) were exacerbation rates and resource utilization (general practitioner visits, hospital admissions). Results From the 44,201 patients in the study cohort, 83.5% were classified into severity levels GOLD A: 33.8%, GOLD B: 21.0%, GOLD C: 18.1%, and GOLD D: 27.0%. Mean age at diagnosis was 66 years and 52.0% were male. Annual exacerbation rates per person-year increased with severity, from 0.83 (95% confidence interval [CI]: 0.81–0.85) for GOLD A to 2.51 (95% CI: 2.47–2.55) for GOLD D. General practitioner visit rates per person-year also increased with severity, from 4.82 (95% CI: 4.74–4.93) for GOLD A to 7.44 (95% CI: 7.31–7.61) for GOLD D. COPD-related hospitalization rates per person-year increased from less symptoms (GOLD A: 0.28, GOLD C: 0.39) to more symptoms (GOLD B: 0.52, GOLD D: 0.84). Conclusion Patients in the most severe category (GOLD D) experienced nearly three times the number of exacerbations and COPD-related hospitalizations as those in the least severe category (GOLD A), in addition to increased general practitioner visits. Better patient management to stabilize the disease progression could allow for an

  3. The Powerful Functions of Peptide-Based Bioactive Matrices for Regenerative Medicine

    PubMed Central

    Rubert Pérez, Charles M.; Stephanopoulos, Nicholas; Sur, Shantanu; Lee, Sungsoo S.; Newcomb, Christina; Stupp, Samuel I.

    2014-01-01

    In an effort to develop bioactive matrices for regenerative medicine, peptides have been used widely to promote interactions with cells and elicit desired behaviors in vivo. This paper describes strategies that utilize peptide-based molecules as building blocks to create supramolecular nanostructures that emulate not only the architecture but also the chemistry of the extracellular matrix in mammalian biology. After initiating a desired regenerative response in vivo, the innate biodegradability of these systems allow for the natural biological processes to take over in order to promote formation of a new tissue without leaving a trace of the nonnatural components. These bioactive matrices can either bind or mimic growth factors or other protein ligands to elicit a cellular response, promote specific mechanobiological responses, and also guide the migration of cells with programmed directionality. In vivo applications discussed in this review using peptide-based matrices include the regeneration of axons after spinal cord injury, regeneration of bone, and the formation of blood vessels in ischemic muscle as a therapy in peripheral arterial disease and cardiovascular diseases. PMID:25366903

  4. An effective conjugation strategy for designing short peptide-based HIV-1 fusion inhibitors.

    PubMed

    Liang, Guodong; Wang, Huixin; Chong, Huihui; Cheng, Siqi; Jiang, Xifeng; He, Yuxian; Wang, Chao; Liu, Keliang

    2016-08-16

    Lengthy peptides corresponding to the C-terminal heptad repeat (C-peptides) of human immunodeficiency virus type 1 (HIV-1) gp41 are potent inhibitors against virus-cell fusion. Designing short C-peptide-based HIV-1 fusion inhibitors could potentially redress the physicochemical and technical liabilities of a long-peptide therapeutic. However, designing such inhibitors with high potency has been challenging. We generated a conjugated architecture by incorporating small-molecule inhibitors of gp41 into the N-terminus of a panel of truncated C-peptides. Among these small molecule-capped short peptides, the 26-residue peptide Indole-T26 inhibited HIV-1 Env-mediated cell-cell fusion and viral replication at low nanomolar levels, reaching the potency of the only clinically used 36-residue peptide T20 (enfuvirtide). Collectively, our work opens up a new avenue for developing short peptide-based HIV-1 fusion inhibitors, and may have broad applicability to the development of modulators of other class I fusion proteins. PMID:27454320

  5. The Supramolecular Organization of a Peptide-Based Nanocarrier at High Molecular Detail.

    PubMed

    Rad-Malekshahi, Mazda; Visscher, Koen M; Rodrigues, João P G L M; de Vries, Renko; Hennink, Wim E; Baldus, Marc; Bonvin, Alexandre M J J; Mastrobattista, Enrico; Weingarth, Markus

    2015-06-24

    Nanovesicles self-assembled from amphiphilic peptides are promising candidates for applications in drug delivery. However, complete high-resolution data on the local and supramolecular organization of such materials has been elusive thus far, which is a substantial obstacle to their rational design. In the absence of precise information, nanovesicles built of amphiphilic "lipid-like" peptides are generally assumed to resemble liposomes that are organized from bilayers of peptides with a tail-to-tail ordering. Using the nanocarrier formed by the amphiphilic self-assembling peptide 2 (SA2 peptide) as an example, we derive the local and global organization of a multimega-Dalton peptide-based nanocarrier at high molecular detail and at close-to physiological conditions. By integrating a multitude of experimental techniques (solid-state NMR, AFM, SLS, DLS, FT-IR, CD) with large- and multiscale MD simulations, we show that SA2 nanocarriers are built of interdigitated antiparallel β-sheets, which bear little resemblance to phospholipid liposomes. Our atomic level study allows analyzing the vesicle surface structure and dynamics as well as the intermolecular forces between peptides, providing a number of potential leads to improve and tune the biophysical properties of the nanocarrier. The herein presented approach may be of general utility to investigate peptide-based nanomaterials at high-resolution and at physiological conditions. PMID:26022089

  6. Active Hydrogenation Catalyst with a Structured, Peptide-Based Outer-Coordination Sphere

    SciTech Connect

    Jain, Avijita; Buchko, Garry W.; Reback, Matthew L.; O'Hagan, Molly J.; Ginovska-Pangovska, Bojana; Linehan, John C.; Shaw, Wendy J.

    2012-10-05

    The synthesis, catalytic activity, and structural features of a rhodium-based hydrogenation catalyst containing a phosphine ligand coupled to a 14-residue peptide are reported. Both CD and NMR spectroscopy show that the peptide adopts a helical structure in 1:1:1 TFE/MeCN/H2O that is maintained when the peptide is attached to the ligand and when the ligand is attached to the metal complex. The metal complex hydrogenates aqueous solutions of 3-butenol to 1-butanol at 360 ± 50 turnovers/Rh/h at 294 K. This peptide- based catalyst represents a starting point for developing and characterizing a peptide-based outer-coordination sphere that can be used to introduce enzyme-like features into molecular catalysts. This work was funded by the US DOE Basic Energy Sciences, Chemical Sciences, Geoscience and Biosciences Division (AJ, JCL and WJS), the Office of Science Early Career Research Program through the Office of Basic Energy Sciences (GWB, MLR and WJS). Part of the research was conducted at the W.R. Wiley Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by U.S. Department of Energy’s Office of Biolog-ical and Environmental Research (BER) program located at Pacific Northwest National Laboratory (PNNL). PNNL is operated by Battelle for the U.S. Department of Energy.

  7. HPV vaccine

    MedlinePlus

    Vaccine - HPV; Immunization - HPV; Gardasil; Cervarix; HPV2; HPV4; Vaccine to prevent cervical cancer ... HPV is a common virus that is spread through sexual contact. There are several types of HPV. ...

  8. Diphtheria Vaccination

    MedlinePlus

    ... and adults - Tetanus-diphtheria-acellular Pertussis vaccine Diphtheria Vaccination Pronounced (dif-THEER-ee-a) Recommend on Facebook ... Related Pages Pertussis Tetanus Feature Story: Adults Need Immunizations, Too Abbreviations DTaP=Pediatric - Diphtheria-Tetanus-acellular Pertussis ...

  9. Giardia vaccination.

    PubMed

    Olson, M E; Ceri, H; Morck, D W

    2000-05-01

    Recently, a Giardia vaccine has become commercially available in the USA for prevention of clinical signs of giardiasis and reduction of cyst shedding in dogs and cats. The vaccine is based upon the current state of knowledge of Giardia antigenicity and immunology. Here, Merle Olson, Howard Ceri and Douglas Morck describe studies that led to the development of this vaccine and subsequent efficacy studies. Immunoprophylaxis and immunotherapeutic application of the vaccine are discussed. PMID:10782082

  10. Who Needs Chickenpox Vaccine

    MedlinePlus

    ... Not Get Chickenpox Vaccine Types of Chickenpox Vaccine Child and Adult Immunization Schedules Possible Side Effects of Chickenpox Vaccine Childcare and School Vaccine Requirements Also Known As & Abbreviations ...

  11. [Diagnosis and therapy of COPD exacerbation].

    PubMed

    Bauer, T T; Nilius, G; Grüning, W; Rasche, K

    2012-04-01

    The acute exacerbation of COPD (AECOPD) is a life-threatening clinical situation. This review summarizes the definition of AECOPD, the severity assessment, typical clinical signs and symptoms, and refers to clinical pitfalls of diagnosis and therapy. Important aspects of clinical history and physical examination in severe exacerbations are reported. The necessary accompanying examinations like chest X-ray, blood gas analysis, ECG and echocardiography and their differential diagnosis as well as therapeutic significance are described. The most important lab examinations are summarized and controversial parameters, e.g., procalcitonin, are commented upon. The differentiated need for a microbiological sputum screening is emphasized. The authors place special weight on the essential components of the therapeutic management of severe AECOPD. Practical aspects of uncontrolled oxygen therapy, drug selection, and application form of inhalative acute therapy, dose, and duration of glucocorticoids, the indication for antibiotics, mechanical ventilation, and also opiates are summarized. PMID:22476704

  12. Menstrual cycle-related exacerbation of disease

    PubMed Central

    Pinkerton, JoAnn V.; Guico-Pabia, Christine J.; Taylor, Hugh S.

    2011-01-01

    Exacerbation of common medical and mental health disorders at specific phases of the menstrual cycle is a prevalent phenomenon. Although the precise cause is unclear, studies implicate complex interactions between the immune and neuroendocrine systems. The menstrual cycle also is a trigger for the onset of depressive disorders, including premenstrual dysphoric disorder, a disorder specific to the luteal phase of the menstrual cycle, and depression associated with the transition to menopause. This article discusses common mental health problems exacerbated by the menstrual cycle, with a particular focus on premenstrual dysphoric disorder and perimenopausal depression. Throughout the reproductive lifespan, routine screening and assessment for the presence of common psychiatric disorders are critical for accurate diagnosis and provision of effective treatment. Management options include referral or consultation with a primary care provider or psychiatrist; treatment options for premenstrual dysphoric disorder and perimenopausal depression include pharmacotherapy with antidepressant agents and/or psychotherapy. Hormones may be helpful. PMID:20207238

  13. Rhinosinusitis and Aspirin-Exacerbated Respiratory Disease

    PubMed Central

    Garcia Cruz, Maria L.; Jimenez-Chobillon, M. Alejandro; Teran, Luis M.

    2012-01-01

    Rhinosinusitis is a feature of aspirin-exacerbated respiratory disease (AERD), which in the initial phase is manifested as nasal congestion, mostly affecting females at the age of around 30 years on average. Subsequently, nasal inflammation progresses to chronic eosinophilic rhinosinusitis, asthma, nasal polyposis, and intolerance to aspirin and to other NSAIDs. While it has been long established that NSAIDs cause inhibition of cyclooxygenase-1 (COX-1), leading to excessive metabolism of arachidonic acid (AA) to cysteinyl-leukotrienes (cys-LTs), there is now evidence that both cytokines and staphylococcus superantigens amplify the inflammatory process exacerbating the disease. This paper gives a brief overview of the development of chronic rhinosinusitis (CRS) in sensitive patients, and we share our experience in the diagnosis and management of CRS in AERD. PMID:22829846

  14. Asthma Exacerbation: An Emergency Medicine Simulation Scenario

    PubMed Central

    Angus, Karen; Parsons, Michael; Cheeseman, Neil

    2015-01-01

    In the practice of emergency medicine, simulation is a valuable tool that allows medical students and postgraduate residents to develop skills in a safe environment at no risk to patients. In this report, we present a case simulation of an acute asthma exacerbation utilizing a human patient simulator. The case is designed such that it can be easily modified to accommodate the trainee’s level of expertise, allowing instructors to challenge both the novice and advanced learner alike. PMID:26180682

  15. Treatment of pulmonary exacerbations in cystic fibrosis - could do better?

    PubMed

    Smyth, Alan

    2016-08-01

    This article describes the nature and significance of pulmonary exacerbations in cystic fibrosis (CF). The effectiveness and safety of current exacerbation treatment are explored. The article concludes with a summary of clinical trials (completed and ongoing) which aim to improve the efficacy and safety of exacerbation treatment. PMID:27349725

  16. DNA vaccines

    NASA Astrophysics Data System (ADS)

    Gregersen, Jens-Peter

    2001-12-01

    Immunization by genes encoding immunogens, rather than with the immunogen itself, has opened up new possibilities for vaccine research and development and offers chances for new applications and indications for future vaccines. The underlying mechanisms of antigen processing, immune presentation and regulation of immune responses raise high expectations for new and more effective prophylactic or therapeutic vaccines, particularly for vaccines against chronic or persistent infectious diseases and tumors. Our current knowledge and experience of DNA vaccination is summarized and critically reviewed with particular attention to basic immunological mechanisms, the construction of plasmids, screening for protective immunogens to be encoded by these plasmids, modes of application, pharmacokinetics, safety and immunotoxicological aspects. DNA vaccines have the potential to accelerate the research phase of new vaccines and to improve the chances of success, since finding new immunogens with the desired properties is at least technically less demanding than for conventional vaccines. However, on the way to innovative vaccine products, several hurdles have to be overcome. The efficacy of DNA vaccines in humans appears to be much less than indicated by early studies in mice. Open questions remain concerning the persistence and distribution of inoculated plasmid DNA in vivo, its potential to express antigens inappropriately, or the potentially deleterious ability to insert genes into the host cell's genome. Furthermore, the possibility of inducing immunotolerance or autoimmune diseases also needs to be investigated more thoroughly, in order to arrive at a well-founded consensus, which justifies the widespread application of DNA vaccines in a healthy population.

  17. Engineering biodegradable and multifunctional peptide-based polymers for gene delivery

    PubMed Central

    2013-01-01

    The complex nature of in vivo gene transfer establishes the need for multifunctional delivery vectors capable of meeting these challenges. An additional consideration for clinical translation of synthetic delivery formulations is reproducibility and scale-up of materials. In this review, we summarize our work over the last five years in developing a modular approach for synthesizing peptide-based polymers. In these materials, bioactive peptides that address various barriers to gene delivery are copolymerized with a hydrophilic backbone of N-(2-hydroxypropyl)methacrylamide (HPMA) using reversible-addition fragmentation chain-transfer (RAFT) polymerization. We demonstrate that this synthetic approach results in well-defined, narrowly-disperse polymers with controllable composition and molecular weight. To date, we have investigated the effectiveness of various bioactive peptides for DNA condensation, endosomal escape, cell targeting, and degradability on gene transfer, as well as the impact of multivalency and polymer architecture on peptide bioactivity. PMID:24156736

  18. Current scenario of peptide-based drugs: the key roles of cationic antitumor and antiviral peptides

    PubMed Central

    Mulder, Kelly C. L.; Lima, Loiane A.; Miranda, Vivian J.; Dias, Simoni C.; Franco, Octávio L.

    2013-01-01

    Cationic antimicrobial peptides (AMPs) and host defense peptides (HDPs) show vast potential as peptide-based drugs. Great effort has been made in order to exploit their mechanisms of action, aiming to identify their targets as well as to enhance their activity and bioavailability. In this review, we will focus on both naturally occurring and designed antiviral and antitumor cationic peptides, including those here called promiscuous, in which multiple targets are associated with a single peptide structure. Emphasis will be given to their biochemical features, selectivity against extra targets, and molecular mechanisms. Peptides which possess antitumor activity against different cancer cell lines will be discussed, as well as peptides which inhibit virus replication, focusing on their applications for human health, animal health and agriculture, and their potential as new therapeutic drugs. Moreover, the current scenario for production and the use of nanotechnology as delivery tool for both classes of cationic peptides, as well as the perspectives on improving them is considered. PMID:24198814

  19. Glutathione-Triggered Formation of a Fmoc-Protected Short Peptide-Based Supramolecular Hydrogel

    PubMed Central

    Shi, Yang; Wang, Jingyu; Wang, Huaimin; Hu, Yanhui; Chen, Xuemei; Yang, Zhimou

    2014-01-01

    A biocompatible method of glutathione (GSH) catalyzed disulfide bond reduction was used to form Fmoc-short peptide-based supramolecular hydrogels. The hydrogels could form in both buffer solution and cell culture medium containing 10% of Fetal Bovine Serum (FBS) within minutes. The hydrogel was characterized by rheology, transmission electron microscopy, and fluorescence emission spectra. Their potential in three dimensional (3D) cell culture was evaluated and the results indicated that the gel with a low concentration of the peptide (0.1 wt%) was suitable for 3D cell culture of 3T3 cells. This study provides an alternative candidate of supramolecular hydrogel for 3D cell culture and cell delivery. PMID:25222132

  20. Sponge-Like Behaviour in Isoreticular Cu(Gly-His-X) Peptide-Based Porous Materials.

    PubMed

    Martí-Gastaldo, Carlos; Warren, John E; Briggs, Michael E; Armstrong, Jayne A; Thomas, K Mark; Rosseinsky, Matthew J

    2015-11-01

    We report two isoreticular 3D peptide-based porous frameworks formed by coordination of the tripeptides Gly-L-His-Gly and Gly-L-His-L-Lys to Cu(II) which display sponge-like behaviour. These porous materials undergo structural collapse upon evacuation that can be reversed by exposure to water vapour, which permits recovery of the original open channel structure. This is further confirmed by sorption studies that reveal that both solids exhibit selective sorption of H2 O while CO2 adsorption does not result in recovery of the original structures. We also show how the pendant aliphatic amine chains, present in the framework from the introduction of the lysine amino acid in the peptidic backbone, can be post-synthetically modified to produce urea-functionalised networks by following methodologies typically used for metal-organic frameworks built from more rigid "classical" linkers. PMID:26406996

  1. Gene introduction into the mitochondria of Arabidopsis thaliana via peptide-based carriers

    NASA Astrophysics Data System (ADS)

    Chuah, Jo-Ann; Yoshizumi, Takeshi; Kodama, Yutaka; Numata, Keiji

    2015-01-01

    Available methods in plant genetic transformation are nuclear and plastid transformations because similar procedures have not yet been established for the mitochondria. The double membrane and small size of the organelle, in addition to its large population in cells, are major obstacles in mitochondrial transfection. Here we report the intracellular delivery of exogenous DNA localized to the mitochondria of Arabidopsis thaliana using a combination of mitochondria-targeting peptide and cell-penetrating peptide. Low concentrations of peptides were sufficient to deliver DNA into the mitochondria and expression of imported DNA reached detectable levels within a short incubation period (12 h). We found that electrostatic interaction with the cell membrane is not a critical factor for complex internalization, instead, improved intracellular penetration of mitochondria-targeted complexes significantly enhanced gene transfer efficiency. Our results delineate a simple and effective peptide-based method, as a starting point for the development of more sophisticated plant mitochondrial transfection strategies.

  2. Generation and Identification of Peptide-Based Monoclonal Antibodies Against Vacuolar Proton Pyrophosphatase of Toxoplasma gondii

    PubMed Central

    Tong, Chengbi; Xiao, Bin; Cheng, Shasha; Li, Wei; Liao, Xiaoqing; Luo, Shuhong

    2015-01-01

    Vacuolar proton pyrophosphatase (V-PPase), an electrogenic proton pump widely distributed in non-mammalian species, is one of the important targets for acidocalcisomes. In this study, a novel method of peptide-based antibody generation was performed to produce monoclonal antibodies (MAbs) against Toxoplasma gondii V-PPase. Three hybridomas were identified and confirmed by ELISA, Western blotting, and immunofluorescence. All of them can react with an 85 kDa band of T. gondii protein in purified acidocalcisomal fraction. The three MAbs were all specific to the synthetic peptide of YTKAADVGADLSGKNEYGMSEDDPRNPAC, corresponding to amino acids at the location of 292aa–320aa of TgVP1 amino acid sequence. These specific MAbs will be valuable tools for further study of T. gondii infection biology, pathogenesis, and host immune response. PMID:26090597

  3. Remineralization of initial enamel caries in vitro using a novel peptide based on amelogenin

    NASA Astrophysics Data System (ADS)

    Li, Danxue; Lv, Xueping; Tu, Huanxin; Zhou, Xuedong; Yu, Haiyang; Zhang, Linglin

    2015-09-01

    Dental caries is the most common oral disease with high incidence, widely spread and can seriously affect the health of oral cavity and the whole body. Current caries prevention measures such as fluoride treatment, antimicrobial agents, and traditional Chinese herbal, have limitations to some extent. Here we design and synthesize a novel peptide based on the amelogenin, and assess its ability to promote the remineralization of initial enamel caries lesions. We used enamel blocks to form initial lesions, and then subjected to 12-day pH cycling in the presence of peptide, NaF and HEPES buffer. Enamel treated with peptide or NaF had shallower, narrower lesions, thicker remineralized surfaces and less mineral loss than enamel treated with HEPES. This peptide can promote the remineralization of initial enamel caries and inhibit the progress of caries. It is a promising anti-caries agent with various research prospects and practical application value.

  4. Sponge-Like Behaviour in Isoreticular Cu(Gly-His-X) Peptide-Based Porous Materials

    PubMed Central

    Martí-Gastaldo, Carlos; Warren, John E; Briggs, Michael E; Armstrong, Jayne A; Thomas, K Mark; Rosseinsky, Matthew J

    2015-01-01

    We report two isoreticular 3D peptide-based porous frameworks formed by coordination of the tripeptides Gly-l-His-Gly and Gly-l-His-l-Lys to CuII which display sponge-like behaviour. These porous materials undergo structural collapse upon evacuation that can be reversed by exposure to water vapour, which permits recovery of the original open channel structure. This is further confirmed by sorption studies that reveal that both solids exhibit selective sorption of H2O while CO2 adsorption does not result in recovery of the original structures. We also show how the pendant aliphatic amine chains, present in the framework from the introduction of the lysine amino acid in the peptidic backbone, can be post-synthetically modified to produce urea-functionalised networks by following methodologies typically used for metal–organic frameworks built from more rigid “classical” linkers. PMID:26406996

  5. Gene introduction into the mitochondria of Arabidopsis thaliana via peptide-based carriers

    PubMed Central

    Chuah, Jo-Ann; Yoshizumi, Takeshi; Kodama, Yutaka; Numata, Keiji

    2015-01-01

    Available methods in plant genetic transformation are nuclear and plastid transformations because similar procedures have not yet been established for the mitochondria. The double membrane and small size of the organelle, in addition to its large population in cells, are major obstacles in mitochondrial transfection. Here we report the intracellular delivery of exogenous DNA localized to the mitochondria of Arabidopsis thaliana using a combination of mitochondria-targeting peptide and cell-penetrating peptide. Low concentrations of peptides were sufficient to deliver DNA into the mitochondria and expression of imported DNA reached detectable levels within a short incubation period (12 h). We found that electrostatic interaction with the cell membrane is not a critical factor for complex internalization, instead, improved intracellular penetration of mitochondria-targeted complexes significantly enhanced gene transfer efficiency. Our results delineate a simple and effective peptide-based method, as a starting point for the development of more sophisticated plant mitochondrial transfection strategies. PMID:25583214

  6. Hepatitis Vaccines

    PubMed Central

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  7. Hepatitis Vaccines.

    PubMed

    Ogholikhan, Sina; Schwarz, Kathleen B

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  8. The clinical management of COPD exacerbations: an update.

    PubMed

    Bonten, Tobias N; Kasteleyn, Marise J; Taube, Christian; Chavannes, Niels H

    2016-01-01

    Clinical management of chronic obstructive pulmonary disease (COPD) exacerbations is of high importance because exacerbations reduce quality of life, increase mortality and carry high socioeconomic costs. Still, a quarter of patients with an acute exacerbation do not respond adequately to initial exacerbation treatment. Yet, research from recent years has advanced the clinical management of COPD exacerbations. Prediction of exacerbations can be improved by asking patients about their exacerbation history. The duration of oral corticosteroid treatment has been optimized, new oral- and inhalation medication has become available and important knowledge has been gathered about the risks and benefits of inhalation corticosteroids, which we will discuss in this editorial. Still, future research is needed to tailor treatment strategies for specific COPD phenotypes. PMID:26512797

  9. Dengue vaccine

    PubMed Central

    Jindal, Harashish; Bhatt, Bhumika; Malik, Jagbir Singh; SK, Shashikantha

    2014-01-01

    Dengue has emerged as one of the major global public health problems. The disease has broken out of its shell and has spread due to increased international travel and climatic changes. Globally, over 2.5 billion people accounting for >40% of the world's population are at risk from dengue. Since the 1940s, dengue vaccines have been under investigation. A live-attenuated tetravalent vaccine based on chimeric yellow fever-dengue virus (CYD-TDV) has progressed to phase III efficacy studies. Dengue vaccine has been found to be a cost-effective intervention to reduce morbidity and mortality. Current dengue vaccine candidates aim to protect against the 4 dengue serotypes, but the recent discovery of a fifth serotype could complicate vaccine development. In recent years, an urgent need has been felt for a vaccine to prevent the morbidity and mortality from this disease in a cost-effective way. PMID:25424928

  10. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  11. Immunomodulatory vaccines against autoimmune diseases.

    PubMed

    Sela, Michael

    2006-01-01

    Vaccines are for healthy people, to prevent them from becoming ill. Such prophylactic vaccines have been a great success. Therapeutic vaccines become more and more important, especially as life expectancy increases. Efforts to develop vaccines against such diseases as cancer, AIDS, hepatitis, tuberculosis, Alzheimer disease, and mad cow disease have not yet reached the stage where they can be successfully used on a daily basis. However, significant progress has been made in the realm of autoimmune diseases, resulting (at least in one case) in an immunomodulatory vaccine against multiple sclerosis that was developed in the author's laboratory, and that is in daily use by about 100,000 patients. The drug or therapeutic vaccine against the exacerbating-remitting type of multiple sclerosis is a copolymer of four amino acid residues, denoted Copaxone, which are related to myelin basic protein. This paper discusses Copaxone as well as a candidate immunomodulatory vaccine against myasthenia gravis, a peptide derived from the nicotinic acetylcholine receptor. Copolymer 1 (Cop 1, glatiramer acetate, Copaxone) is a synthetic amino acid random copolymer that is immunologically cross-reactive with myelin basic protein and suppresses experimental allergic encephalomyelitis in several animal species. Cop 1 slows the progression of disability and reduces the relapse rate in exacerbating-remitting multiple sclerosis patients. Cop 1 is a potent inducer of T helper 2 (Th2) regulatory cells in mice and humans; and Th2 cells are found in both the brains and spinal cords of Cop 1-treated mice and humans. MG and experimental autoimmune MG are T cell-regulated, antibody-mediated autoimmune diseases. Two peptides, representing sequences of the human AChR-alpha-subunit, p195-212 and p259-271, are immunodominant T-cell epitopes in MG patients and two strains of mice. Altered peptide ligand, composed of the randomly arranged two single amino acid analogs inhibits in vitro and in vivo MG

  12. Impact of Prolonged Exacerbation Recovery in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Law, Martin; Kowlessar, Beverly; Singh, Richa; Brill, Simon E.; Allinson, James P.; Wedzicha, Jadwiga A.

    2015-01-01

    Rationale: Exacerbations are important and heterogeneous events in the natural history of chronic obstructive pulmonary disease (COPD). Objectives: To examine the consequences of prolonged exacerbation recovery in patients with COPD. Methods: A cohort of 384 patients with COPD (FEV1 % predicted 45.8 [SD, 16.6] and a median exacerbation rate of 2.13 per year [interquartile range, 1.0–3.2]) were followed for 1,039 days (interquartile range, 660–1,814) between October 1995 and January 2013. Patients recorded daily worsening of respiratory symptoms and peak expiratory flow (PEF), and when stable underwent spirometry every 3 months, and completed the St. George’s Respiratory Questionnaire annually. Exacerbations were diagnosed as 2 consecutive days with one major symptom plus another respiratory symptom. Exacerbation duration was defined as the time from onset to the day preceding 2 consecutive symptom-free days and recovery in PEF as return to preexacerbation levels. Measurements and Main Results: A total of 351 patients had one or more exacerbations. Patients with a longer symptom duration (mean, 14.5 d) had a worse St. George’s Respiratory Questionnaire total score (0.2 units per 1 day; P = 0.040). A longer symptomatic duration was associated with a shorter interval between exacerbation recovery and onset of the next exacerbation (hazard ratio, 1.004; P = 0.013). For 257 (7.3%) exacerbations, PEF did not recover within 99 days. These exacerbations were associated with symptoms of a viral infection (cold and sore throat). Patients with these nonrecovered exacerbations showed a 10.8 ml/yr (P < 0.001) faster decline in FEV1. Conclusions: Prolonged exacerbation symptomatic duration is associated with poorer health status and a greater risk of a new event. Exacerbations where lung function does not recover are associated with symptoms of viral infections and accelerated decline in FEV1. PMID:26151174

  13. Seasonal Risk Factors for Asthma Exacerbations among Inner City Children

    PubMed Central

    Teach, Stephen J.; Gergen, Peter J.; Szefler, Stanley J.; Mitchell, Herman E.; Calatroni, Agustin; Wildfire, Jeremy; Bloomberg, Gordon; Kercsmar, Carolyn; Liu, Andrew H.; Makhija, Melanie; Matsui, Elizabeth; Morgan, Wayne; O'Connor, George; Busse, William W.

    2015-01-01

    Background Exacerbations of asthma remain common even in children and adolescents despite optimal medical management. Identification of host risk factors for exacerbations is incomplete, particularly for seasonal episodes. Objective Define host risk factors for asthma exacerbations unique to their season of occurrence. Methods This is a retrospective analysis of patients aged 6-20 years who comprised the control groups of the Asthma Control Evaluation trial and the Inner City Anti-IgE Therapy for Asthma trial. Univariate and multivariate models were constructed to determine if patient demographic and historical factors, allergic sensitization, fractional exhaled nitric oxide, spirometric measurements, asthma control, and treatment requirements were associated with seasonal exacerbations. Results The analysis included 400 patients (54.5% male; 59.0% African American; median age 13 years). Exacerbations occurred in 37.5% of participants over the periods of observation and were most common in the fall (28.8% of participants). In univariate analysis, impaired pulmonary function was significantly associated with greater odds of exacerbations for all seasons, as was an exacerbation in the previous season for all seasons except spring. In multivariate analysis, exacerbation in the previous season was the strongest predictor in fall and winter while a higher requirement for inhaled corticosteroids was the strongest predictor in spring and summer. The multivariate models had the best predictive power for fall exacerbations (30.5% variance attributed). Conclusions Among a large cohort of inner city children with asthma, patient risk factors for exacerbations vary by season. Thus, individual patient information may be beneficial in strategies to prevent these seasonal events. Clinical Implications Inner city children remain at risk for asthma exacerbations despite appropriate therapy. Because their risk factors vary by season, strategies to prevent them may need to differ as

  14. Development of Cross-Protective Influenza A Vaccines Based on Cellular Responses

    PubMed Central

    Soema, Peter Christiaan; van Riet, Elly; Kersten, Gideon; Amorij, Jean-Pierre

    2015-01-01

    Seasonal influenza vaccines provide protection against matching influenza A virus (IAV) strains mainly through the induction of neutralizing serum IgG antibodies. However, these antibodies fail to confer a protective effect against mismatched IAV. This lack of efficacy against heterologous influenza strains has spurred the vaccine development community to look for other influenza vaccine concepts, which have the ability to elicit cross-protective immune responses. One of the concepts that is currently been worked on is that of influenza vaccines inducing influenza-specific T cell responses. T cells are able to lyse infected host cells, thereby clearing the virus. More interestingly, these T cells can recognize highly conserved epitopes of internal influenza proteins, making cellular responses less vulnerable to antigenic variability. T cells are therefore cross-reactive against many influenza strains, and thus are a promising concept for future influenza vaccines. Despite their potential, there are currently no T cell-based IAV vaccines on the market. Selection of the proper antigen, appropriate vaccine formulation and evaluation of the efficacy of T cell vaccines remains challenging, both in preclinical and clinical settings. In this review, we will discuss the current developments in influenza T cell vaccines, focusing on existing protein-based and novel peptide-based vaccine formulations. Furthermore, we will discuss the feasibility of influenza T cell vaccines and their possible use in the future. PMID:26029218

  15. HPV Vaccine

    MedlinePlus

    ... can cause problems like genital warts and some kinds of cancer, a vaccine is an important step in preventing infection and protecting against the spread of HPV. That's why doctors recommend that all girls and guys get the vaccine at these ages: ...

  16. Rotavirus Vaccine

    MedlinePlus

    Why get vaccinated?Rotavirus is a virus that causes diarrhea, mostly in babies and young children. The diarrhea can be severe, and lead ... and fever are also common in babies with rotavirus.Before rotavirus vaccine, rotavirus disease was a common ...

  17. Anthrax Vaccine

    MedlinePlus

    ... products some military personnel, as determined by the Department of Defense These people should get five doses of vaccine ( ... cdc.gov/agent/anthrax/vaccination/. Contact the U.S Department of Defense (DoD): call 1-877-438-8222 or visit ...

  18. Identification of SNAIL1 Peptide-Based Irreversible Lysine-Specific Demethylase 1-Selective Inactivators.

    PubMed

    Itoh, Yukihiro; Aihara, Keisuke; Mellini, Paolo; Tojo, Toshifumi; Ota, Yosuke; Tsumoto, Hiroki; Solomon, Viswas Raja; Zhan, Peng; Suzuki, Miki; Ogasawara, Daisuke; Shigenaga, Akira; Inokuma, Tsubasa; Nakagawa, Hidehiko; Miyata, Naoki; Mizukami, Tamio; Otaka, Akira; Suzuki, Takayoshi

    2016-02-25

    Inhibition of lysine-specific demethylase 1 (LSD1), a flavin-dependent histone demethylase, has recently emerged as a new strategy for treating cancer and other diseases. LSD1 interacts physically with SNAIL1, a member of the SNAIL/SCRATCH family of transcription factors. This study describes the discovery of SNAIL1 peptide-based inactivators of LSD1. We designed and prepared SNAIL1 peptides bearing a propargyl amine, hydrazine, or phenylcyclopropane moiety. Among them, peptide 3, bearing hydrazine, displayed the most potent LSD1-inhibitory activity in enzyme assays. Kinetic study and mass spectrometric analysis indicated that peptide 3 is a mechanism-based LSD1 inhibitor. Furthermore, peptides 37 and 38, which consist of cell-membrane-permeable oligoarginine conjugated with peptide 3, induced a dose-dependent increase of dimethylated Lys4 of histone H3 in HeLa cells, suggesting that they are likely to exhibit LSD1-inhibitory activity intracellularly. In addition, peptide 37 decreased the viability of HeLa cells. We believe this new approach for targeting LSD1 provides a basis for development of potent selective inhibitors and biological probes for LSD1. PMID:26700437

  19. Self-assembled peptide-based hydrogels as scaffolds for anchorage-dependent cells.

    PubMed

    Zhou, Mi; Smith, Andrew M; Das, Apurba K; Hodson, Nigel W; Collins, Richard F; Ulijn, Rein V; Gough, Julie E

    2009-05-01

    We report here the design of a biomimetic nanofibrous hydrogel as a 3D-scaffold for anchorage-dependent cells. The peptide-based bioactive hydrogel is formed through molecular self-assembly and the building blocks are a mixture of two aromatic short peptide derivatives: Fmoc-FF (Fluorenylmethoxycarbonyl-diphenylalanine) and Fmoc-RGD (arginine-glycine-aspartate) as the simplest self-assembling moieties reported so far for the construction of small-molecule-based bioactive hydrogels. This hydrogel provides a highly hydrated, stiff and nanofibrous hydrogel network that uniquely presents bioactive ligands at the fibre surface; therefore it mimics certain essential features of the extracellular matrix. The RGD sequence as part of the Fmoc-RGD building block plays a dual role of a structural component and a biological ligand. Spectroscopic and imaging analysis using CD, FTIR, fluorescence, TEM and AFM confirmed that FF and RGD peptide sequences self-assemble into beta-sheets interlocked by pi-pi stacking of the Fmoc groups. This generates the cylindrical nanofibres interwoven within the hydrogel with the presence of RGDs in tunable densities on the fibre surfaces. This rapid gelling material was observed to promote adhesion of encapsulated dermal fibroblasts through specific RGD-integrin binding, with subsequent cell spreading and proliferation; therefore it may offer an economical model scaffold to 3D-culture other anchorage-dependent cells for in-vitro tissue regeneration. PMID:19201459

  20. Predicting the composition of red wine blends using an array of multicomponent Peptide-based sensors.

    PubMed

    Ghanem, Eman; Hopfer, Helene; Navarro, Andrea; Ritzer, Maxwell S; Mahmood, Lina; Fredell, Morgan; Cubley, Ashley; Bolen, Jessica; Fattah, Rabia; Teasdale, Katherine; Lieu, Linh; Chua, Tedmund; Marini, Federico; Heymann, Hildegarde; Anslyn, Eric V

    2015-01-01

    Differential sensing using synthetic receptors as mimics of the mammalian senses of taste and smell is a powerful approach for the analysis of complex mixtures. Herein, we report on the effectiveness of a cross-reactive, supramolecular, peptide-based sensing array in differentiating and predicting the composition of red wine blends. Fifteen blends of Cabernet Sauvignon, Merlot and Cabernet Franc, in addition to the mono varietals, were used in this investigation. Linear Discriminant Analysis (LDA) showed a clear differentiation of blends based on tannin concentration and composition where certain mono varietals like Cabernet Sauvignon seemed to contribute less to the overall characteristics of the blend. Partial Least Squares (PLS) Regression and cross validation were used to build a predictive model for the responses of the receptors to eleven binary blends and the three mono varietals. The optimized model was later used to predict the percentage of each mono varietal in an independent test set composted of four tri-blends with a 15% average error. A partial least square regression model using the mouth-feel and taste descriptive sensory attributes of the wine blends revealed a strong correlation of the receptors to perceived astringency, which is indicative of selective binding to polyphenols in wine. PMID:26007178

  1. Schistosomiasis vaccines

    PubMed Central

    Siddiqui, Bilal A.; Ganley-Leal, Lisa

    2011-01-01

    Schistosomiasis is a major neglected tropical disease of public health importance to a billion people. An estimated 200 million people are currently infected; an additional 779 million individuals are at risk to acquire the infection in 74 countries. Despite many years of implementation of mass anti-parasitic drug therapy programs and other control measures, this disease has not been contained and continues to spread to new geographic areas.  The discovery of a protective vaccine still remains the most potentially effective means for the control of this disease, especially if the vaccine provides long-term immunity against the infection. A vaccine would contribute to the reduction of schistosomiasis morbidity through induced immune responses leading to decrease in parasite load and reduced egg production. This vaccine could be administered to children between the ages of 3 and 12 years to prevent severe infection in a particularly high risk population. This review summarizes the current status of schistosomiasis vaccine development. PMID:22048120

  2. Typhoid vaccines.

    PubMed

    Aggarwal, A; Dutta, A K

    2001-08-01

    Typhoid fever continues to be a major public health problem in developing countries with about 33 million cases per year. Protective efficacy of traditional acetone/phenol killed vaccines is similar to newer typhoid vaccines (Ty21A and Vi antigen vaccine) but side effects of these newer vaccines are considerably less. Though the mortality is low, typhoid fever causes considerable morbidity and loss of working days. Problems during treatment are increasing due to emergence and spread of multidrug resistant S. typhi. Hence to decrease the incidence of typhoid fever in addition to ensuring safe water supply and excreta disposal a typhoid vaccine needs to be introduced in the National Immunization Schedule. PMID:11563251

  3. Impact of COPD exacerbation on cerebral blood flow.

    PubMed

    Yildiz, Sema; Kaya, Ihsan; Cece, Hasan; Gencer, Mehmet; Ziylan, Zeki; Yalcin, Funda; Turksoy, Ozlem

    2012-01-01

    We aimed to investigate the impact of chronic obstructive pulmonary disease (COPD) exacerbation on cerebral blood flow (CBF). In 21 COPD patients - in both exacerbation and stable phases -Doppler ultrasonographies of internal carotid artery (ICA) and vertebral artery (VA) were performed. There were significant differences in total, anterior and posterior CBF, ICA and VA flow volumes in exacerbated COPD compared to stable COPD. Total CBF was correlated with cross-sectional areas of left and right ICA, whereas independent predictor of total CBF was cross-sectional area of right ICA. Increased CBF might indicate cerebral autoregulation-mediated vasodilatation to overcome COPD exacerbation induced hypoxia. PMID:22542376

  4. Applying the Concept of Peptide Uniqueness to Anti-Polio Vaccination

    PubMed Central

    Kanduc, Darja; Fasano, Candida; Capone, Giovanni; Pesce Delfino, Antonella; Calabrò, Michele; Polimeno, Lorenzo

    2015-01-01

    Background. Although rare, adverse events may associate with anti-poliovirus vaccination thus possibly hampering global polio eradication worldwide. Objective. To design peptide-based anti-polio vaccines exempt from potential cross-reactivity risks and possibly able to reduce rare potential adverse events such as the postvaccine paralytic poliomyelitis due to the tendency of the poliovirus genome to mutate. Methods. Proteins from poliovirus type 1, strain Mahoney, were analyzed for amino acid sequence identity to the human proteome at the pentapeptide level, searching for sequences that (1) have zero percent of identity to human proteins, (2) are potentially endowed with an immunologic potential, and (3) are highly conserved among poliovirus strains. Results. Sequence analyses produced a set of consensus epitopic peptides potentially able to generate specific anti-polio immune responses exempt from cross-reactivity with the human host. Conclusion. Peptide sequences unique to poliovirus proteins and conserved among polio strains might help formulate a specific and universal anti-polio vaccine able to react with multiple viral strains and exempt from the burden of possible cross-reactions with human proteins. As an additional advantage, using a peptide-based vaccine instead of current anti-polio DNA vaccines would eliminate the rare post-polio poliomyelitis cases and other disabling symptoms that may appear following vaccination. PMID:26568962

  5. Immunomodulatory treatments for aspirin exacerbated respiratory disease

    PubMed Central

    Moebus, Rachel G.

    2012-01-01

    Background: Aspirin triad is a subclass of chronic sinusitis characterized by nasal polyposis, nonallergic induced asthma, and aspirin sensitivity. Also known as Samter's triad or aspirin-exacerbated respiratory disease, aspirin triad commonly affects the adult population and is seldom found in pediatric patients. Methods: This rhinosinusitis has multiple layers of pathological process, but the ultimate predicament is caused by cysteinyl leukotrienes (cysLTs). Results: Pharmacotherapies include oral steroid, lipoxygenase inhibitor, and cysLT receptor inhibitor drugs, which can provide some relief for these patients. Conclusion: Immunomodulation via aspirin desensitization is considered when pharmacotherapy has failed. When aspirin triad is unmanageable with medical treatment alone, endoscopic sinus surgery with polypectomy can alleviate the patient's symptoms, allowing for a better response to postoperative medical management such as topical medication as well as delivery of topical medications. PMID:22487291

  6. [Treatment of multiple sclerosis symptoms and exacerbations].

    PubMed

    Prieto González, José María

    2014-12-01

    In the last few years, there has been an explosion of new drugs acting on the clinical course of multiple sclerosis (MS) but less attention has been paid to better knowledge of the symptoms of this disease and their pathogenesis and treatment, which is essential to improve patients' quality of life. Because many patients have numerous concurrent symptoms during their clinical course, their management is complex and consequently it is important to know which symptoms are a direct result of the degenerative lesions of MS. The present article describes all the therapeutic options available for spasticity and its associated pain, paroxystic symptoms, fatigue, genitourinary disorders and sexual dysfunction, tremor, ataxia, gait disorder and cognitive impairment, with special emphasis on novel treatments. The article also defines exacerbations, how to recognize them and the available treatments, mainly oral administration of high-dose methylprednisolone and plasmapheresis. PMID:25732949

  7. Simulated Aeromedical Evacuation Exacerbates Experimental Brain Injury.

    PubMed

    Skovira, Jacob W; Kabadi, Shruti V; Wu, Junfang; Zhao, Zaorui; DuBose, Joseph; Rosenthal, Robert; Fiskum, Gary; Faden, Alan I

    2016-07-15

    Aeromedical evacuation, an important component in the care of many patients with traumatic brain injury (TBI), particularly in war zones, exposes them to prolonged periods of hypobaria. The effects of such exposure on pathophysiological changes and outcome after TBI are largely unexplored. The objective of this study was to investigate whether prolonged hypobaria in rats subjected to TBI alters behavioral and histological outcomes. Adult male Sprague-Dawley rats underwent fluid percussion induced injury at 1.5-1.9 atmospheres of pressure. The effects of hypobaric exposure (6 h duration; equivalent to 0.75 atmospheres) at 6, 24, and 72 h, or 7 days after TBI were evaluated with regard to sensorimotor, cognitive, and histological changes. Additional groups were evaluated to determine the effects of two hypobaric exposures after TBI, representing primary simulated aeromedical evacuation (6 h duration at 24 h after injury) and secondary evacuation (10 h duration at 72 h after injury), as well as the effects of 100% inspired oxygen concentrations during simulated evacuation. Hypobaric exposure up to 7 days after injury significantly worsened cognitive deficits, hippocampal neuronal loss, and microglial/astrocyte activation in comparison with injured controls not exposed to hypobaria. Hyperoxia during hypobaric exposure or two exposures to prolonged hypobaric conditions further exacerbated spatial memory deficits. These findings indicate that exposure to prolonged hypobaria up to 7 days after TBI, even while maintaining physiological oxygen concentration, worsens long-term cognitive function and neuroinflammation. Multiple exposures or use of 100% oxygen further exacerbates these pathophysiological effects. PMID:26593382

  8. Rotavirus vaccines.

    PubMed

    Barnes, G

    1998-01-01

    Encouraging results have been reported from several large trials of tetravalent rhesus rotavirus vaccine, with efficacy of 70-80% against severe disease. A recent Venezuelan study showed similar results to trials in USA and Europe. The vaccine may soon be licensed in USA. It provides the exciting prospect of a strategy to prevent one of the world's major child killers. Other candidate vaccines are under development including human-bovine reassortants, neonatal strains, non-replicating rotaviruses, vector vaccines and other genetically engineered products. Second and third generation rotavirus vaccines are on the horizon. The need for a rotavirus vaccine is well accepted by paediatricians, but public health authorities need to be lobbied. Other issues which need to be addressed include relative importance of non-group A rotaviruses, possible administration with OPV, the influence of breast feeding, and most importantly, cost. It is essential that rotavirus vaccine is somehow made available to all of the world's children, not just those in developed countries. PMID:9553287

  9. Recent trends in pH/thermo-responsive self-assembling hydrogels: from polyions to peptide-based polymeric gelators.

    PubMed

    Chassenieux, Christophe; Tsitsilianis, Constantinos

    2016-02-01

    In this article, we highlight some recent developments in "smart" physical hydrogels achieved by self-assembling of block type macromolecules. More precisely we focus on two interesting types of gelators namely conventional ionic (or ionogenic) block copolymers and peptide-based polymers having as a common feature their responsiveness to pH and/or temperature which are the main triggers used for potential biomedical applications. Taking advantage of the immense skills of conventional block copolymer hydrogelators, namely macromolecular design, self-assembling mechanism, gel rheological properties, responsiveness to various triggers and innovative applications, the development of novel self-assembling gelators, integrating the new knowledge emerging from the peptide-based systems, opens new horizons towards bio-inspired technologies. PMID:26781351

  10. Highly sensitive and selective detection of Al(III) ions in aqueous buffered solution with fluorescent peptide-based sensor.

    PubMed

    In, Byunggyu; Hwang, Gi Won; Lee, Keun-Hyeung

    2016-09-15

    A fluorescent sensor based on a tripeptide (SerGluGlu) with a dansyl fluorophore detected selectively Al(III) among 16 metal ions in aqueous buffered solutions without any organic cosolvent. The peptide-based sensor showed a highly sensitive turn on response to aluminium ion with high binding affinity (1.84×10(4)M(-1)) in aqueous buffered solutions. The detection limit (230nM, 5.98ppb) of the peptide-based sensor was much lower than the maximum allowable level (7.41μM) of aluminium ions in drinking water demanded by EPA. The binding mode of the peptide sensor with aluminium ions was characterized using ESI mass spectrometry, NMR titration, and pH titration experiments. PMID:27503680

  11. [Rabbies vaccination].

    PubMed

    Jelinek, Tomas

    2016-01-01

    With very few exceptions, rabies is occurring around the globe. The clinical course of this mammal-transmitted infection is almost universally fatal. Thus, the disease is causing more human deaths than any other zoonosis. Due to the lack of effective therapeutic options, pre- or post-exposure vaccination remains the only effective means to avoid development of fatal disease. Save and highly effective cell culture vaccines which have been available for decades provide long-lasting protection. Various vaccination schedules have been tested and are being recommended. PMID:27268449

  12. PEP-on-DEP: A competitive peptide-based disposable electrochemical aptasensor for renin diagnostics.

    PubMed

    Biyani, Manish; Kawai, Keiko; Kitamura, Koichiro; Chikae, Miyuki; Biyani, Madhu; Ushijima, Hiromi; Tamiya, Eiichi; Yoneda, Takashi; Takamura, Yuzuru

    2016-10-15

    Antibody-based immunosensors are relatively less accessible to a wide variety of unreachable targets, such as low-molecular-weight biomarkers that represent a rich untapped source of disease-specific diagnostic information. Here, we present a peptide aptamer-based electrochemical sensor technology called 'PEP-on-DEP' to detect less accessible target molecules, such as renin, and to improve the quality of life. Peptide-based aptamers represent a relatively smart class of affinity binders and show great promise in biosensor development. Renin is involved in the regulation of arterial blood pressure and is an emerging biomarker protein for predicting cardiovascular risk and prognosis. To our knowledge, no studies have described aptamer molecules that can be used as new potent probes for renin. Here, we describe a portable electrochemical biosensor platform based on the newly identified peptide aptamer molecules for renin. We constructed a randomized octapeptide library pool with diversified sequences and selected renin specific peptide aptamers using cDNA display technology. We identified a few peptide aptamer sequences with a KD in the µM binding affinity range for renin. Next, we grafted the selected peptide aptamers onto gold nanoparticles and detected renin in a one-step competitive assay using our originally developed DEP (Disposable Electrochemical Printed) chip and a USB powered portable potentiostat system. We successfully detected renin in as little as 300ngmL(-1) using the PEP-on-DEP method. Thus, the generation and characterization of novel probes for unreachable target molecules by merging a newly identified peptide aptamer with electrochemical transduction allowed for the development of a more practical biosensor that, in principle, can be adapted to develop a portable, low-cost and mass-producible biosensor for point-of-care applications. PMID:26746799

  13. C6 Peptide-Based Multiplex Phosphorescence Analysis (PHOSPHAN) for Serologic Confirmation of Lyme Borreliosis

    PubMed Central

    Pomelova, Vera G.; Korenberg, Edward I.

    2015-01-01

    Background A single-tier immunoassay using the C6 peptide of VlsE (C6) from Borrelia burgdorferi sensu stricto (Bb) has been proposed as a potential alternative to conventional two-tier testing for the serologic diagnosis of Lyme disease in the United States and Europe. Objective To evaluate the performance of C6 peptide based multiplex Phosphorescence Analysis (PHOSPHAN) for the serologic confirmation of Lyme borreliosis (LB) in Russian patients. Methods Serum samples (n = 351) were collected from 146 patients with erythema migrans (EM); samples from 131 of these patients were taken several times prior to treatment and at different stages of recovery. The control group consisted of 197 healthy blood donors and 31 patients with other diseases, all from the same highly endemic region of Russia. All samples were analyzed by PHOSPHAN for IgM and IgG to Bb C6, recombinant OspC and VlsE proteins, and C6 peptides from B. garinii and B. afzelii. Results IgM and IgG to Bb C6 were identified in 43 and 95 out of 131 patients (32.8 and 72.5%, respectively); seroconversion of IgM antibodies was observed in about half of the patients (51.2%), and of IgG antibodies, in almost all of them (88.4%). Additional detection of OspC-IgM and VlsE-IgM or IgG to C6 from B. garinii or B. afzelii did not contribute significantly to the overall sensitivity of the multiplex immunoassay. Conclusions The multiplex phosphorescence immunoassay is a promising method for simultaneously revealing the spectrum of antibodies to several Borrelia antigens. Detection of IgM and IgG to Bb C6 in the sera of EM patients provides effective serologic confirmation of LB and, with high probability, indicates an active infection process. PMID:26147441

  14. Anti-biofilm and sporicidal activity of peptides based on wheat puroindoline and barley hordoindoline proteins.

    PubMed

    Shagaghi, Nadin; Alfred, Rebecca L; Clayton, Andrew H A; Palombo, Enzo A; Bhave, Mrinal

    2016-07-01

    The broad-spectrum activity of antimicrobial peptides (AMPs) and low probability of development of host resistance make them excellent candidates as novel bio-control agents. A number of AMPs are found to be cationic, and a small proportion of these are tryptophan-rich. The puroindolines (PIN) are small, basic proteins found in wheat grains with proposed roles in biotic defence of seeds and seedlings. Synthetic peptides based on their unique tryptophan-rich domain (TRD) display antimicrobial properties. Bacterial endospores and biofilms are highly resistant cells, with significant implications in both medical and food industries. In this study, the cationic PIN TRD-based peptides PuroA (FPVTWRWWKWWKG-NH2 ) and Pina-M (FSVTWRWWKWWKG-NH2 ) and the related barley hordoindoline (HIN) based Hina (FPVTWRWWTWWKG-NH2 ) were tested for effects on planktonic cells and biofilms of the common human pathogens including Pseudomonas aeruginosa, Listeria monocytogenes and the non-pathogenic Listeria innocua. All peptides showed significant bactericidal activity. Further, PuroA and Pina-M at 2 × MIC prevented initial biomass attachment by 85-90% and inhibited >90% of 6-h preformed biofilms of all three organisms. However Hina, with a substitution of Lys-9 with uncharged Thr, particularly inhibited Listeria biofilms. The PIN based peptides were also tested against vegetative cells and endospores of Bacillus subtilis. The results provided evidence that these tryptophan-rich peptides could kill B. subtilis even in sporulated state, reducing the number of viable spores by 4 log units. The treated spores appeared withered under scanning electron microscopy. The results establish the potential of these tryptophan-rich peptides in controlling persistent pathogens of relevance to food industries and human health. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID:27238815

  15. Long-term Prognosis in COPD Exacerbation: Role of Biomarkers, Clinical Variables and Exacerbation Type.

    PubMed

    Grolimund, Eva; Kutz, Alexander; Marlowe, Robert J; Vögeli, Alaadin; Alan, Murat; Christ-Crain, Mirjam; Thomann, Robert; Falconnier, Claudine; Hoess, Claus; Henzen, Christoph; Zimmerli, Werner; Mueller, Beat; Schuetz, Philipp

    2015-06-01

    Long-term outcome prediction in COPD is challenging. We conducted a prospective 5-7-year follow-up study in patients with COPD to determine the association of exacerbation type, discharge levels of inflammatory biomarkers including procalctionin (PCT), C-reactive protein (CRP), white blood cell count (WBC) and plasma proadrenomedullin (ProADM), alone or combined with demographic/clinical characteristics, with long-term all-cause mortality in the COPD setting. The analyzed cohort comprised 469 patients with index hospitalization for pneumonic (n = 252) or non-pneumonic (n = 217) COPD exacerbation. Five-to-seven-year vital status was ascertained via structured phone interviews with patients or their household members/primary care physicians. We investigated predictive accuracy using univariate and multivariate Cox regression models and area under the receiver operating characteristic curve (AUC). After a median [25th-75th percentile] 6.1 [5.6-6.5] years, mortality was 55% (95%CI 50%-59%). Discharge ProADM concentration was strongly associated with 5-7-year non-survival: adjusted hazard ratio (HR)/10-fold increase (95%CI) 10.4 (6.2-17.7). Weaker associations were found for PCT and no significant associations were found for CRP or WBC. Combining ProADM with demographic/clinical variables including age, smoking status, BMI, New York Heart Association dyspnea class, exacerbation type, and comorbidities significantly improved long-term predictive accuracy over that of the demographic/clinical model alone: AUC (95%CI) 0.745 (0.701-0.789) versus 0.727 (0.681-0.772), (p) = .043. In patients hospitalized for COPD exacerbation, discharge ProADM levels appeared to accurately predict 5-7-year all-cause mortality and to improve long-term prognostic accuracy of multidimensional demographic/clinical mortality risk assessment. PMID:25230352

  16. Arthropod vaccines.

    PubMed

    Lee, R; Opdebeeck, J P

    1999-03-01

    Antigens located in the midgut of the tick are hidden from the host's immune system. Egg production of ticks can be reduced when ticks are fed on animals vaccinated with midgut antigens of the tick, and a subunit vaccine formulated with the recombinant antigen Bm86 is now available that can reduce the number of ticks infesting cattle grazing on pasture. Midgut antigens used in vaccines against insects that transmit pathogenic organisms to humans have not been as effective in reducing insect fecundity and an alternative approach may be necessary. Transmission-blocking vaccines directed at interfering with the vector-pathogen interaction could result in loss of vector competence and block the spread of disease-causing organisms. PMID:10198800

  17. Typhoid Vaccine

    MedlinePlus

    ... serious disease. It is caused by bacteria called Salmonella Typhi. Typhoid causes a high fever, fatigue, weakness, ... a typhoid carrier. • Laboratory workers who work with Salmonella Typhi bacteria. Inactivated typhoid vaccine (shot) • One dose ...

  18. Meningococcal Vaccines

    MedlinePlus

    ... is an infection of the covering of the brain and the spinal cord. Meningococcal disease also causes ... legs, have problems with their nervous systems, become deaf or mentally ... use of meningococcal vaccine is important for people at highest risk.

  19. The causes and consequences of seasonal variation in COPD exacerbations.

    PubMed

    Donaldson, Gavin C; Wedzicha, Jadwiga A

    2014-01-01

    The time of year when patients experience exacerbations of chronic obstructive pulmonary disease is a much-overlooked feature of the disease. The higher incidence of exacerbations in winter has important consequences for patients in terms of increased morbidity and mortality. The seasonality also imposes a considerable burden on already-overloaded health care services, with both primary care consultations and hospital admissions increasing in number. The seasonality of exacerbations varies with latitude, and is greater in more temperate climates, where there may be less protection from outdoor and indoor cold exposure. The precise causes of the seasonality are unknown, but thought to be partly due to the increased prevalence of respiratory viral infections circulating in cold, damp conditions. Increased susceptibility to viral infection may also be a mechanism mediated through increased airway inflammation or possibly reduced vitamin D levels. The seasonality of exacerbations informs us about the triggers of exacerbations and suggests possible strategies to reduce their number. PMID:25336941

  20. The causes and consequences of seasonal variation in COPD exacerbations

    PubMed Central

    Donaldson, Gavin C; Wedzicha, Jadwiga A

    2014-01-01

    The time of year when patients experience exacerbations of chronic obstructive pulmonary disease is a much-overlooked feature of the disease. The higher incidence of exacerbations in winter has important consequences for patients in terms of increased morbidity and mortality. The seasonality also imposes a considerable burden on already-overloaded health care services, with both primary care consultations and hospital admissions increasing in number. The seasonality of exacerbations varies with latitude, and is greater in more temperate climates, where there may be less protection from outdoor and indoor cold exposure. The precise causes of the seasonality are unknown, but thought to be partly due to the increased prevalence of respiratory viral infections circulating in cold, damp conditions. Increased susceptibility to viral infection may also be a mechanism mediated through increased airway inflammation or possibly reduced vitamin D levels. The seasonality of exacerbations informs us about the triggers of exacerbations and suggests possible strategies to reduce their number. PMID:25336941

  1. Mepolizumab for the reduction of exacerbations in severe eosinophilic asthma.

    PubMed

    Russell, Richard; Brightling, Christopher

    2016-06-01

    Asthma affects over 300 million people worldwide and is severe in 10% of sufferers. Severe asthma is associated with greater morbidity and mortality particularly as a consequence of frequent exacerbations. Advances in approaches to phenotype the heterogeneity of severe asthma has established the importance of eosinophilic inflammation and emerging new therapies are broadly designed to target T2-mediated eosinophilic inflammation with the aim to reduce exacerbation frequency. Here, we summarize the evidence that eosinophilic asthma is an important pheno(endo)type and identifies a group at risk of exacerbations; that established therapies reduce exacerbations, particularly in eosinophilic severe asthma; and discuss the role of mepolizumab, an IL-5 neutralising monoclonal antibody therapy, in reducing exacerbations in severe eosinophilic asthma compared to established and other emerging therapies. PMID:27058452

  2. Ear Infection and Vaccines

    MedlinePlus

    ... an ENT Doctor Near You Ear Infection and Vaccines Ear Infection and Vaccines Patient Health Information News ... or may need reinsertion over time. What about vaccines? A vaccine is a preparation administered to stimulate ...

  3. Adults Need Vaccines, Too!

    MedlinePlus

    ... turn JavaScript on. Feature: Adult Vaccinations Adults Need Vaccines, Too! Past Issues / Summer 2015 Table of Contents ... of the millions of adults not receiving the vaccines you need? What vaccines do you need? All ...

  4. Live Virus Smallpox Vaccine

    MedlinePlus

    ... Index SMALLPOX FACT SHEET The Live Virus Smallpox Vaccine The vaccinia virus is the "live virus" used ... cannot cause smallpox. What is a "live virus" vaccine? A "live virus" vaccine is a vaccine that ...

  5. Pertussis (Whooping Cough) Vaccination

    MedlinePlus

    ... Tetanus-diphtheria-acellular Pertussis vaccine Pertussis (Whooping Cough) Vaccination Pronounced (per-TUS-iss) Recommend on Facebook Tweet ... The best way to prevent it is through vaccinations. The childhood vaccine is called DTaP. The whooping ...

  6. Promoting Vaccine Confidence.

    PubMed

    Smith, Michael J

    2015-12-01

    Vaccine hesitancy incorporates a wide range of parental attitudes and behaviors surrounding vaccines. Ironically, the very success of the immunization program has fueled vaccine concerns; because vaccine-preventable diseases are no longer prevalent, attention has shifted to the safety and necessity of vaccines themselves. This article reviews some of the underlying themes of vaccine hesitancy as well as specific vaccine safety concerns. Strategies for discussing vaccines with concerned parents are also discussed. PMID:26337737

  7. Outcomes associated with acute exacerbations of chronic obstructive pulmonary disorder requiring hospitalization

    PubMed Central

    Gaude, Gajanan S; Rajesh, BP; Chaudhury, Alisha; Hattiholi, Jyothi

    2015-01-01

    Background: Acute exacerbations of chronic obstructive pulmonary disorder (AECOPD) are known to be associated with increased morbidity and mortality and have a significant socioeconomic impact. The factors that determine frequent hospital readmissions for AECOPD are poorly understood. The present study was done to ascertain failures rates following AECOPD and to evaluate factors associated with frequent readmissions. Materials and Methods: We conducted a prospective study among 186 patients with COPD with one or more admissions for acute exacerbations in a tertiary care hospital. Frequency of previous re-admissions for AECOPD in the past year, and clinical characteristics, including spirometry were ascertained in the stable state both before discharge and at 6-month post-discharge. Failure rates following treatment were ascertained during the follow-up period. All the patients were followed up for a period of 2 years after discharge to evaluate re-admissions for the AECOPD. Results: Of 186 COPD patients admitted for AECOPD, 54% had one or more readmission, and another 45% had two or more readmissions over a period of 2 years. There was a high prevalence of current or ex-heavy smokers, associated co-morbidity, underweight patients, low vaccination prevalence and use of domiciliary oxygen therapy among COPD patients. A total of 12% mortality was observed in the present study. Immediate failure rates after first exacerbation was observed to be 34.8%. Multivariate analysis showed that duration >20 years (OR = 0.37; 95% CI: 0.10-0.86), use of Tiotropium (OR = 2.29; 95% CI: 1.12-4.69) and use of co-amoxiclav during first admission (OR = 2.41; 95% CI: 1.21-4.79) were significantly associated with higher immediate failure rates. The multivariate analysis for repeated admissions revealed that disease duration >10 years (OR = 0.50; 95% CI: 0.27-0.93), low usage of inhaled ICS + LABA (OR = 2.21; 95% CI: 1.08-4.54), and MRC dyspnea grade >3 (OR = 2.51; 95% CI: 1.08-5.82) were

  8. Dexrazoxane exacerbates doxorubicin-induced testicular toxicity.

    PubMed

    Levi, Mattan; Tzabari, Moran; Savion, Naphtali; Stemmer, Salomon M; Shalgi, Ruth; Ben-Aharon, Irit

    2015-10-01

    Infertility induced by anti-cancer treatments pose a major concern for cancer survivors. Doxorubicin (DXR) has been previously shown to exert toxic effects on the testicular germinal epithelium. Based upon the cardioprotective traits of dexrazoxane (DEX), we studied its potential effect in reducing DXR-induced testicular toxicity. Male mice were injected with 5  mg/kg DXR, 100  mg/kg DEX, combination of both or saline (control) and sacrificed either 1, 3 or 6 months later. Testes were excised and further processed. Glutathione and apoptosis assays were performed to determine oxidative stress. Immunohistochemistry and confocal microscopy were used to study the effects of the drugs on testicular histology and on spermatogonial reserve. DXR and the combined treatment induced a striking decline in testicular weight. DEX prevented DXR-induced oxidative stress, but enhanced DXR-induced apoptosis within the testes. Furthermore, the combined treatment depleted the spermatogonial reserve after 1 month, with impaired recovery at 3 and 6 months post-treatment. This resulted in compromised sperm parameters, testicular and epididymal weights as well as significantly reduced sperm motility, all of which were more severe than those observed in DXR-treated mice. The activity of DEX in the testis may differ from its activity in cardiomyocytes. Adding DEX to DXR exacerbates DXR-induced testicular toxicity. PMID:26329125

  9. Platelets in aspirin-exacerbated respiratory disease

    PubMed Central

    Laidlaw, Tanya M.; Boyce, Joshua A.

    2015-01-01

    Aspirin-exacerbated respiratory disease (AERD) is a chronic inflammatory disease characterized clinically by the triad of asthma, nasal polyposis, and pathognomonic respiratory reactions after ingestion of aspirin. It is a distinct syndrome associated with eosinophilic infiltration of respiratory tissues and excessive production of cysteinyl leukotrienes. Despite the consistent clinical phenotype of the respiratory disease, the underlying pathogenesis of the disease remains unclear. In addition to their role in hemostasis, platelets have the capacity to influence the activation state and function of other immune cells during inflammation, and to facilitate granulocyte recruitment into the tissues. Platelets also possess a repertoire of potent pre-formed mediators of inflammation that are released upon activation, and are a rich source of newly-synthesized lipid mediators that alter vascular permeability and smooth muscle tone. Accordingly, the activity of platelets has been linked to diverse inflammatory diseases, including asthma. Both human and animal studies strongly suggest that platelet activity is uniquely associated with the pathophysiology of AERD. This article summarizes the evidence supporting an effector role for platelets in asthma in general and in AERD in particular, and considers the potential therapeutic implications. PMID:26051947

  10. Alzheimer's Disease: An Exacerbation of Senile Phenoptosis.

    PubMed

    Isaev, N K; Stelmashook, E V; Genrikhs, E E; Oborina, M V; Kapkaeva, M R; Skulachev, V P

    2015-12-01

    Alzheimer's disease is characterized by progressive memory loss and cognitive decline accompanied by degeneration of neuronal synapses, massive loss of neurons in the brain, eventually resulting in complete degradation of personality and death. Currently, the cause of the disease is not fully understood, but it is believed that the person's age is the major risk factor for development of Alzheimer's disease. People who have survived after cerebral stroke or traumatic brain injury have substantially increased risk of developing Alzheimer's disease. Social exclusion, low social activity, physical inactivity, poor mental performance, and low level of education are among risk factors for development of this neurodegenerative disease, which is consistent with the concept of phenoptosis (Skulachev, V. P., et al. (1999) Biochemistry (Moscow), 64, 1418-1426; Skulachev, M. V., and Skulachev, V. P. (2014) Biochemistry (Moscow), 79, 977-993) stating that rate of aging is related to psychological and social aspects in human behavior. Here we assumed that Alzheimer's disease might be considered as an exacerbation of senile phenoptosis. If so, then development of this disease could be slowed using mitochondria-targeted antioxidants due to the accumulated data demonstrating a link between mitochondrial dysfunction and oxidative stress both with normal aging and Alzheimer's disease. PMID:26638682

  11. Peptide-based gemini amphiphiles: phase behavior and rheology of wormlike micelles.

    PubMed

    Shrestha, Rekha Goswami; Nomura, Kazuyuki; Yamamoto, Masashi; Yamawaki, Yukio; Tamura, Yoshinaga; Sakai, Kenichi; Sakamoto, Kazutami; Sakai, Hideki; Abe, Masahiko

    2012-11-01

    Aqueous binary phase behavior of a peptide-based gemini amphiphile with glutamic acid and lysine as spacer group, acylglutamyllysilacylglutamate (m-GLG-m where m = 12, 14, and 16), has been reported over a wide range of concentration and temperature. Lauroylglutamyllysillauroylglutamate, 12-GLG-12, self-assembles into spherical micelles above critical micelle concentration (CMC). The micellar region extends up to 32 wt %, and an ordering of spherical micelles into micellar cubic phase, I(1), takes place at 33 wt % at 25 °C. The phase transition, I(1) - hexagonal liquid crystal, (H(1)) - lamellar liquid crystal, (L(α)) has been observed with further increase in concentration; moreover, mixed phases are also observed between the pure liquid crystal domains. Similar phases were observed with 16-GLG-16 above 50 °C (Krafft temperature). The partial ternary phase behavior shows that the micellar solutions of m-GLG-m can solubilize a large amount of cationic amphiphile, alkyltrimethylammonium bromide, C(n)TAB, (where n = 14 (TTAB) and 16 (CTAB)) at 25 °C. An addition of C(n)TAB to the aqueous solutions of 16-GLG-16 in a dilute region forms a transparent solution of viscoelastic wormlike micelles at very low concentration (0.25 wt %) even at ambient condition. A mixture of oppositely charged amphiphiles, m-GLG-m and C(n)TAB, exhibits synergism as a result the amphiphile layer curvature, becomes less positive, and favors the transition from sphere to rod to transient networks (wormlike micelles). The gemini amphiphile, 16-GLG-16, forms wormlike micelles at relatively low concentrations compared to others reported so far. Viscosity increases by six orders of magnitude compared to that of pure solvent. The hydrophobic chain length of m-GLG-m and coamphiphile affects the rheology; the maximum viscosity achieved with 16-GLG-16/H(2)O/CTAB is higher than that of 14-GLG-14/H(2)O/CTAB, 12-GLG-12/H(2)O/CTAB, and 16-GLG-16/H(2)O/TTAB systems. These temperature-sensitive systems

  12. Development of collagen peptide-based biomaterials for tissue engineering applications

    NASA Astrophysics Data System (ADS)

    Hernandez Gordillo, Victor

    The transition from in vitro to in vivo use of stem cells in regenerative medicine requires biomaterial scaffolds that can maintain stem cell viability and at the same time allow cell differentiation. We have previously reported the design of a collagen mimetic peptide (CMP) that assembles into a mesh-like three-dimensional (3D) structure upon the addition of metal ions and its potential for the culture of human cells. The addition of a chelating solution, such as EDTA, results in disassembly of the 3D structure, demonstrating the flexibility in the assembly/disassembly process. In the second chapter of this dissertation, we report the design of CMPs that can be functionalized with His-tagged cargoes within the 3D scaffold, via metal coordination. We show that the addition of GFP-His8 and human epidermal growth factor (hEGF-His6) has minimal effect in the assembly process. Additionally, we show that the bound hEGF-His6 can be released gradually in vitro for 5 days and induces cell proliferation in an EGF-dependent cell line. Furthermore, we functionalized the CMPs with the cell adhesion sequence (RGDS) to promote cell differentiation of two human non-tumorigenic cells lines, MCF10A and 3522-S1. In the third chapter, we evaluated the possibility of using the collagen mimetic-peptide-based (CMP) scaffolds for cell encapsulation and differentiation of human mesenchymal stem cells (hMSC). We show that hMSC encapsulated within the CMP scaffold are viable for up to 24 days post encapsulation. Moreover, hMSC at days 1, 4 and 8 days after encapsulation can be recovered from the scaffold and retain their stemness properties when analyzed for in vitro differentiation. We also demonstrate by real time PCR (RT-PCR) that genes important for osteogenic and chondrogenic differentiation are over-expressed in the absence of stimulating factors when the cells are encapsulated in the 3D scaffold at 8 and 24 days post encapsulation. Lastly, the incorporation of the cell adhesion

  13. VACCINATION--COLLECTIVE RESPONSIBILITY OR VIOLATION OF RIGHTS?

    PubMed

    Florescu, Laura; Rugina, Aurica; Temneanu, Oana Raluca; Paduraru, Dana Teodora Anton; Matei, Mioara Calipsoana; Safta, Cosmin; Mindru, Dana Elena

    2015-01-01

    Vaccination is considered to be the most effective and the cheapest medical intervention through which individual and collective immunisation is achieved. Statistics show that, at present, immunisation annually saves 400 million lives and protects approximately 750,000 children against disabilities of varying degrees. Approximately 80% of worldwide children are vaccinated against diphtheria, tetanus, pertussis, polio, measles, etc.; these diseases used to be considered incurable in the past. Vaccines help the body to produce antibodies; they help the immune system to detect germs and inactivate their cells. The immunological protection is installed after a variable period of time following the inoculation and is long lasting. Immunisations can be achieved in several ways: through national immunisation campaigns with general recommendation--they may be compulsory, optional or prophylactic (for the diseases for which a vaccine is available); vaccinations not included in the compulsory immunisation programmes; they may also be targeted to the contagious infectious outbreaks or to groups of population in certain situations. There is no guarantee that a vaccine will provide 100% protection. However, it will significantly reduce the risk of getting an infection. Vaccines have side effects which can be divided into reactions triggered by the vaccine or reactions exacerbated by it, without a causal relationship to the vaccine. PMID:26793855

  14. New insights for development of a safe and protective RSV vaccine.

    PubMed

    Blanco, Jorge C G; Boukhvalova, Marina S; Shirey, Kari Ann; Prince, Gregory A; Vogel, Stefanie N

    2010-06-01

    Respiratory Syncytial Virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants and children <1 year old, resulting in significant morbidity and mortality worldwide. There is currently no RSV vaccine. In the 1960s, a formalin-inactivated RSV (FI-RSV) vaccine trial led to exacerbated disease upon natural infection of vaccinees, including two deaths. The causes involved in the disastrous results of these vaccine trials are still unclear but they remain the engine for searching new avenues to develop a safe vaccine that can provide long-term protection against this important pathogen. This article reviews some of the early history of RSV vaccine development,as well as more recent information on the interaction between RSV and the host innate and adaptive immune responses. A safe and efficacious vaccine for RSV will require "re-education" of the host immune response against RSV to prevent vaccine-enhanced or severe RSV disease. PMID:20671419

  15. Using Poly I:C as an adjuvant does not induce or exacerbate models of systemic lupus erythematosus.

    PubMed

    Annable, Tami; Tomassian, Tamar; Jain, Siddhartha; Leibbrandt, Martha; Cooke, Michael P; Deane, Jonathan A

    2015-02-01

    Subunit vaccines are typically poorly immunogenic when administered alone, and require adjuvants for robust responses. Triggering TLRs to boost antigen-specific adaptive immunity is an attractive approach to increase the potency and quality of vaccines. However, recent reports suggest that alterations in TLR expression are associated with the pathogenesis of inflammatory and autoimmune diseases. To compare genetic studies with adjuvant studies, we examined whether stimulation through a TLR agonist induces or increases the autoimmune phenotype of healthy or autoimmune mice. C57BL/6, MRL/lpr, and Fcγr2b-deficient mice were dosed i.p. with Poly I:C every other day for 3 weeks, and monitored for signs of autoimmunity over 3 months. A separate group of mice was vaccinated three times i.m. with rPA anthrax antigen with or without Poly I:C with 2 weeks between doses. Immunized groups exhibited robust responses to vaccine and C57BL/6 and MRL/lpr mice showed a statistically significant increase in anti-rPA IgG responses in the presence of Poly I:C. Interestingly, Fcγr2b-/- mice showed increases with the base rPA vaccine, which was not significantly increased when Poly I:C was used as an adjuvant. In the chronically dosed groups, we also observed subtle alterations in levels of total antibody and some autoantibodies. However, there were no statistically significant differences in autoimmune syndrome, as measured by proteinurea, kidney pathology, weight loss, and mortality, with Poly I:C administration in chronic or vaccination mode. Taken together, these results suggest that administration of TLR3 agonists in chronic or vaccination mode does not induce or exacerbate models of systemic lupus erythematosus. PMID:25483245

  16. Cancer vaccines

    PubMed Central

    2015-01-01

    Cancer vaccines are designed to promote tumor specific immune responses, particularly cytotoxic CD8 positive T cells that are specific to tumor antigens. The earliest vaccines, which were developed in 1994-95, tested non-mutated, shared tumor associated antigens that had been shown to be immunogenic and capable of inducing clinical responses in a minority of people with late stage cancer. Technological developments in the past few years have enabled the investigation of vaccines that target mutated antigens that are patient specific. Several platforms for cancer vaccination are being tested, including peptides, proteins, antigen presenting cells, tumor cells, and viral vectors. Standard of care treatments, such as surgery and ablation, chemotherapy, and radiotherapy, can also induce antitumor immunity, thereby having cancer vaccine effects. The monitoring of patients’ immune responses at baseline and after standard of care treatment is shedding light on immune biomarkers. Combination therapies are being tested in clinical trials and are likely to be the best approach to improving patient outcomes. PMID:25904595

  17. Chronic obstructive pulmonary disease exacerbations: latest evidence and clinical implications

    PubMed Central

    Qureshi, Hammad; Sharafkhaneh, Amir

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. The natural history of COPD is punctuated by exacerbations which have major short- and long-term implications on the patient and healthcare system. Evidence-based guidelines stipulate that early detection and prompt treatment of exacerbations are essential to ensure optimal outcomes and to reduce the burden of COPD. Several factors can identify populations at risk of exacerbations. Implementing prevention measures in patients at risk is a major goal in the management of COPD. PMID:25177479

  18. Mucosal vaccines

    PubMed Central

    Nizard, Mevyn; Diniz, Mariana O; Roussel, Helene; Tran, Thi; Ferreira, Luis CS; Badoual, Cecile; Tartour, Eric

    2014-01-01

    The mucosal immune system displays several adaptations reflecting the exposure to the external environment. The efficient induction of mucosal immune responses also requires specific approaches, such as the use of appropriate administration routes and specific adjuvants and/or delivery systems. In contrast to vaccines delivered via parenteral routes, experimental, and clinical evidences demonstrated that mucosal vaccines can efficiently induce local immune responses to pathogens or tumors located at mucosal sites as well as systemic response. At least in part, such features can be explained by the compartmentalization of mucosal B and T cell populations that play important roles in the modulation of local immune responses. In the present review, we discuss molecular and cellular features of the mucosal immune system as well as novel immunization approaches that may lead to the development of innovative and efficient vaccines targeting pathogens and tumors at different mucosal sites. PMID:25424921

  19. Synthetic Long Peptide Influenza Vaccine Containing Conserved T and B Cell Epitopes Reduces Viral Load in Lungs of Mice and Ferrets

    PubMed Central

    Rosendahl Huber, S. K.; Camps, M. G. M.; Jacobi, R. H. J.; Mouthaan, J.; van Dijken, H.; van Beek, J.; Ossendorp, F.; de Jonge, J.

    2015-01-01

    Currently licensed influenza vaccines mainly induce antibodies against highly variable epitopes. Due to antigenic drift, protection is subtype or strain-specific and regular vaccine updates are required. In case of antigenic shifts, which have caused several pandemics in the past, completely new vaccines need to be developed. We set out to develop a vaccine that provides protection against a broad range of influenza viruses. Therefore, highly conserved parts of the influenza A virus (IAV) were selected of which we constructed antibody and T cell inducing peptide-based vaccines. The B epitope vaccine consists of the highly conserved HA2 fusion peptide and M2e peptide coupled to a CD4 helper epitope. The T epitope vaccine comprises 25 overlapping synthetic long peptides of 26-34 amino acids, thereby avoiding restriction for a certain MHC haplotype. These peptides are derived from nucleoprotein (NP), polymerase basic protein 1 (PB1) and matrix protein 1 (M1). C57BL/6 mice, BALB/c mice, and ferrets were vaccinated with the B epitopes, 25 SLP or a combination of both. Vaccine-specific antibodies were detected in sera of mice and ferrets and vaccine-specific cellular responses were measured in mice. Following challenge, both mice and ferrets showed a reduction of virus titers in the lungs in response to vaccination. Summarizing, a peptide-based vaccine directed against conserved parts of influenza virus containing B and T cell epitopes shows promising results for further development. Such a vaccine may reduce disease burden and virus transmission during pandemic outbreaks. PMID:26046664

  20. Vaccination against respiratory Pseudomonas aeruginosa infection

    PubMed Central

    Grimwood, Keith; Kyd, Jennelle M; Owen, Suzzanne J; Massa, Helen M; Cripps, Allan W

    2014-01-01

    Respiratory infections caused by Pseudomonas aeruginosa are a major clinical problem globally, particularly for patients with chronic pulmonary disorders, such as those with cystic fibrosis (CF), non-CF bronchiectasis (nCFB) and severe chronic obstructive pulmonary disease (COPD). In addition, critically ill and immunocompromised patients are also at significant risk of P. aeruginosa infection. For almost half a century, research efforts have focused toward development of a vaccine against infections caused by P. aeruginosa, but a licensed vaccine is not yet available. Significant advances in identifying potential vaccine antigens have been made. Immunisations via both the mucosal and systemic routes have been trialled in animal models and their effectiveness in clearing acute infections demonstrated. The challenge for translation of this research to human applications remains, since P. aeruginosa infections in the human respiratory tract can present both as an acute or chronic infection. In addition, immunisation prior to infection may not be possible for many patients with CF, nCFB or COPD. Therefore, development of a therapeutic vaccine provides an alternative approach for treatment of chronic infection. Preliminary animal and human studies suggest that mucosal immunisation may be effective as a therapeutic vaccine against P. aeruginosa respiratory infections. Nevertheless, more research is needed to improve our understanding of the basic biology of P. aeruginosa and the mechanisms needed to upregulate the induction of host immune pathways to prevent infection. Recognition of variability in the host immune responses for a range of patient health conditions at risk from P. aeruginosa infection is also required to support development of a successful vaccine delivery strategy and vaccine. Activation of mucosal immune responses may provide improved efficacy of vaccination for P. aeruginosa during both acute exacerbations and chronic infection. PMID:25483510

  1. Prediction of short term re-exacerbation in patients with acute exacerbation of chronic obstructive pulmonary disease

    PubMed Central

    Liu, Dong; Peng, Shao-Hua; Zhang, Jing; Bai, Si-Hong; Liu, Hai-Xia; Qu, Jie-Ming

    2015-01-01

    Background The objective of the study is to develop a scoring system for predicting a 90-day re-exacerbation in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Methods A total of 176 consecutive hospitalized patients with AECOPD were included. The sociodemographic characteristics, status before acute exacerbation (AE), presentations of and treatment for the current AE, and the re-exacerbation in 90 days after discharge from hospital were collected. Results The re-exacerbation rate in 90 days was 48.9% (86 out of 176). It was associated with the degree of lung function impairment (Global initiative for chronic Obstructive Lung Disease [GOLD] grades), frequency of AE in the previous year, and parameters of the current AE, including pleural effusion, use of accessory respiratory muscles, inhaled long-acting β-2-agonists, inhaled corticosteroids, controlled oxygen therapy, noninvasive mechanical ventilation, and length of hospital stay, but was not associated with body mass index, modified Medical Research Council scale, or chronic obstructive pulmonary disease assessment test. A subgroup of ten variables was selected and developed into the re-exacerbation index scoring system (age grades, GOLD grades, AE times in the previous year, pleural effusion, use of accessory respiratory muscles, noninvasive mechanical ventilation, controlled oxygen therapy, inhaled long-acting β-2-agonists and inhaled corticosteroids, and length of hospital stay). The re-exacerbation index showed good discrimination for re-exacerbation, with a C-statistic of 0.750 (P<0.001). Conclusion A comprehensive assessment integrating parameters of stable chronic obstructive pulmonary disease, clinical presentations at exacerbation, and treatment showed a strong predictive capacity for short-term outcome in patients with AECOPD. Further studies are required to verify these findings. PMID:26170655

  2. Synthesis of Peptide-Based Hybrid Nanobelts with Enhanced Color Emission by Heat Treatment or Water Induction.

    PubMed

    Liu, Xingcen; Zhu, Pengli; Fei, Jinbo; Zhao, Jie; Yan, Xuehai; Li, Junbai

    2015-06-22

    We demonstrate that an inorganic lanthanide ion (Tb(3+)) or organic dye molecules were encapsulated in situ into diphenylalanine (FF) organogels by a general, simple, and efficient co-assembly process, which generated peptide-based hybrid nanobelts with a range of colored emissions. In the presence of a photosensitizer (salicylic acid), the organogel can serve as an excellent molecular-donor scaffold to investigate FRET to Tb(3+). More importantly, heat treatment or water induction instigated a morphology transition from nanofibers to nanobelts, after which the participation of guest molecules in the FF assembly was promoted and the stability and photoluminescence emission of the composite organogels were enhanced. PMID:25965918

  3. Phenytoin induced Stevens-Johnson syndrome exacerbated by cefepime

    PubMed Central

    Prabhu, Varsha A.; Doddapaneni, Sahiti; Thunga, Girish; Thiyagu, Rajakannan; Prabhu, M. Mukyaprana; Naha, Kushal

    2013-01-01

    Steven Johnson syndrome (SJS) is a rare drug induced mucocutaneous reaction. Here, we present an elaborate report of a 28-year-old female patient who developed Phenytoin induced SJS, which was exacerbated by cefepime. PMID:24250210

  4. Airway Microbiome Dynamics in Exacerbations of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Sethi, Sanjay; Murphy, Timothy; Nariya, Snehal; Boushey, Homer A.; Lynch, Susan V.

    2014-01-01

    Specific bacterial species are implicated in the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD). However, recent studies of clinically stable COPD patients have demonstrated a greater diversity of airway microbiota, whose role in acute exacerbations is unclear. In this study, temporal changes in the airway microbiome before, at the onset of, and after an acute exacerbation were examined in 60 sputum samples collected from subjects enrolled in a longitudinal study of bacterial infection in COPD. Microbiome composition and predicted functions were examined using 16S rRNA-based culture-independent profiling methods. Shifts in the abundance (≥2-fold, P < 0.05) of many taxa at exacerbation and after treatment were observed. Microbiota members that were increased at exacerbation were primarily of the Proteobacteria phylum, including nontypical COPD pathogens. Changes in the bacterial composition after treatment for an exacerbation differed significantly among the therapy regimens clinically prescribed (antibiotics only, oral corticosteroids only, or both). Treatment with antibiotics alone primarily decreased the abundance of Proteobacteria, with the prolonged suppression of some microbiota members being observed. In contrast, treatment with corticosteroids alone led to enrichment for Proteobacteria and members of other phyla. Predicted metagenomes of particular microbiota members involved in these compositional shifts indicated exacerbation-associated loss of functions involved in the synthesis of antimicrobial and anti-inflammatory products, alongside enrichment in functions related to pathogen-elicited inflammation. These trends reversed upon clinical recovery. Further larger studies will be necessary to determine whether specific compositional or functional changes detected in the airway microbiome could be useful indicators of exacerbation development or outcome. PMID:24850358

  5. Rabies Vaccine

    MedlinePlus

    ... and booster doses should be given as needed. (Testing or booster doses are not recommended for travelers.) Ask your doctor for details. Vaccination After an Exposure:Anyone who has been bitten by an animal, or who otherwise may have been exposed to ...

  6. Valuing vaccination

    PubMed Central

    Bärnighausen, Till; Bloom, David E.; Cafiero-Fonseca, Elizabeth T.; O’Brien, Jennifer Carroll

    2014-01-01

    Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery. PMID:25136129

  7. Vexing Vaccines

    ERIC Educational Resources Information Center

    Bowman, Darcia Harris

    2004-01-01

    Schools play a key role in ensuring that children are being immunized against diseases, but conflicting research is making enforcement difficult. This article discusses a growing trend of vaccine avoidance and the endless supply of conflicting information and research about immunization safety. Despite the controversy, many people appear to accept…

  8. Typhoid Vaccine

    MedlinePlus

    ... it while traveling. Typhoid strikes about 21 million people a year around the world and kills about 200,000. ... booster dose is needed every 2 years for people who remain at risk. Live typhoid vaccine (oral)Four doses: one capsule every other day for a week (day 1, day 3, day ...

  9. Polio Vaccine

    MedlinePlus

    ... of the world. It would only take one person infected with polio virus coming from another country to bring the ... However, any medicine could cause a serious side effect, such as a severe allergic reaction or even death. The risk of polio vaccine causing serious harm is extremely small.

  10. Malaria vaccine.

    PubMed

    1994-05-01

    Some have argued that the vaccine against malaria developed by Manuel Pattaroyo, a Colombian scientist, is being tested prematurely in humans and that it is unlikely to be successful. While the Pattaroyo vaccine has been shown to confer protection against the relatively mild malaria found in Colombia, doubts exist over whether it will be effective in Africa. Encouraging first results, however, are emerging from field tests in Tanzania. The vaccine triggered a strong new immune response, even in individuals previously exposed to malaria. Additional steps must be taken to establish its impact upon mortality and morbidity. Five major trials are underway around the world. The creator estimates that the first ever effective malaria vaccine could be available for widespread use within five years and he has no intention of securing a patent for the discovery. In another development, malaria specialists from 35 African countries convened at an international workshop in Zimbabwe to compare notes. Participants disparaged financial outlays for the fight against malaria equivalent to 2% of total AIDS funding as insufficient; noted intercountry differences in prevention, diagnosis, and treatment; and found information exchange between anglophone and francophone doctors to be generally poor. PMID:12287671

  11. Replicating vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early work on fish immunology and disease resistance demonstrated fish (like animals and humans) that survived infection were typically resistant to re-infection with the same pathogen. The concepts of resistance upon reinfection lead to the research and development of replicating (live) vaccines in...

  12. Plasma biomarker profiles in acute exacerbation of idiopathic pulmonary fibrosis

    PubMed Central

    Calfee, Carolyn S.; Wolters, Paul J.; Song, Jin Woo; Hong, Sang-Bum; Brady, Sandra; Ishizaka, Akitoshi; Jones, Kirk D.; King, Talmadge E.; Matthay, Michael A.; Kim, Dong Soon

    2010-01-01

    Little is known about the pathobiology of acute exacerbation of idiopathic pulmonary fibrosis (IPF), a condition that shares clinical and histopathological features with acute lung injury. Plasma biomarkers have been well studied in acute lung injury and have provided insight into the underlying disease mechanism. The objective of this study was to determine the plasma biomarker profile of acute exacerbation of IPF and compare this profile with that of stable IPF and acute lung injury. Plasma was collected from patients with stable IPF, acute exacerbation of IPF, and acute lung injury for measurement of biomarkers of cellular activity/injury (receptor for advanced glycation endproducts, surfactant protein D, KL-6, von Willebrand factor), systemic inflammation (IL-6), and coagulation/fibrinolysis (protein C, thrombomodulin, plasminogen activator inhibitor-1). Plasma from patients with acute exacerbation of IPF showed significant elevations in markers of type II alveolar epithelial cell injury and/or proliferation, endothelial cell injury, and coagulation. This profile differed from the biomarker profile in patients with acute lung injury. These findings support the hypothesis that type II alveolar epithelial cells are centrally involved in the pathobiology of acute exacerbation of IPF. Furthermore, they suggest that acute exacerbation of IPF has a distinct plasma biomarker profile from that of acute lung injury. PMID:20418386

  13. Summarization vs Peptide-Based Models in Label-Free Quantitative Proteomics: Performance, Pitfalls, and Data Analysis Guidelines.

    PubMed

    Goeminne, Ludger J E; Argentini, Andrea; Martens, Lennart; Clement, Lieven

    2015-06-01

    Quantitative label-free mass spectrometry is increasingly used to analyze the proteomes of complex biological samples. However, the choice of appropriate data analysis methods remains a major challenge. We therefore provide a rigorous comparison between peptide-based models and peptide-summarization-based pipelines. We show that peptide-based models outperform summarization-based pipelines in terms of sensitivity, specificity, accuracy, and precision. We also demonstrate that the predefined FDR cutoffs for the detection of differentially regulated proteins can become problematic when differentially expressed (DE) proteins are highly abundant in one or more samples. Care should therefore be taken when data are interpreted from samples with spiked-in internal controls and from samples that contain a few very highly abundant proteins. We do, however, show that specific diagnostic plots can be used for assessing differentially expressed proteins and the overall quality of the obtained fold change estimates. Finally, our study also illustrates that imputation under the "missing by low abundance" assumption is beneficial for the detection of differential expression in proteins with low abundance, but it negatively affects moderately to highly abundant proteins. Hence, imputation strategies that are commonly implemented in standard proteomics software should be used with care. PMID:25827922

  14. Peptide-based methods for assembling and controlling the morphologies, metrics, and properties of gold nanoparticle superstructures

    NASA Astrophysics Data System (ADS)

    Zhang, Chen

    This dissertation describes new peptide-based methods for assembling and controlling the morphologies, metrics, and properties of gold nanoparticle superstructures. The aim of this research is to develop the peptide-based method by modifying the peptide sequences and controlling the reaction conditions for the synthesis and assembly of gold nanoparticle superstructures to achieve reliable control over their morphology and metrics, and furthermore study their properties and applications. With this goal in mind, the C-terminus of a gold-binding peptide was modified with different numbers of hydrophobic phenylalanines to affect peptide assembly and ultimately nanoparticle assembly. The addition of hydrophobic phenylalanines to the C-terminus of peptide conjugates promoted fiber bundling which in turn lead to the formation of thick or intertwined 1-D nanoparticle superstructures. Furthermore, I prepared spherical gold nanoparticle superstructures with varied diameters (˜40nm, ˜75nm, and ˜150nm) and visible to near-infrared optical properties by using a single peptide conjugate molecule yet varied reaction conditions. Theoretical simulation and experiment were coupled to further understand their optical properties. Finally, I studied and demonstrated the drug storage and release properties of hollow spherical gold nanoparticle superstructures; this was the first demonstrated application of this class of nanoparticle superstructure.

  15. Enhancing the Activity of Peptide-Based Artificial Hydrolase with Catalytic Ser/His/Asp Triad and Molecular Imprinting.

    PubMed

    Wang, Mengfan; Lv, Yuqi; Liu, Xiaojing; Qi, Wei; Su, Rongxin; He, Zhimin

    2016-06-01

    In this study, an artificial hydrolase was developed by combining the catalytic Ser/His/Asp triad with N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF), followed by coassembly of the peptides into nanofibers (CoA-HSD). The peptide-based nanofibers provide an ideal supramolecular framework to support the functional groups. Compared with the self-assembled catalytic nanofibers (SA-H), which contain only the catalytic histidine residue, the highest activity of CoA-HSD occurs when histidine, serine, and aspartate residues are at a ratio of 40:1:1. This indicates that the well-ordered nanofiber structure and the synergistic effects of serine and aspartate residues contribute to the enhancement in activity. Additionally, for the first time, molecular imprinting was applied to further enhance the activity of the peptide-based artificial enzyme (CoA-HSD). p-NPA was used as the molecular template to arrange the catalytic Ser/His/Asp triad residues in the proper orientation. As a result, the activity of imprinted coassembled CoA-HSD nanofibers is 7.86 times greater than that of nonimprinted CoA-HSD and 13.48 times that of SA-H. PMID:27191381

  16. The development of Army relevant peptide-based surface enhanced Raman scattering (SERS) sensors for biological threat detection

    NASA Astrophysics Data System (ADS)

    Farrell, Mikella E.; Strobbia, Pietro; Sarkes, Deborah A.; Stratis-Cullum, Dimitra N.; Cullum, Brian M.; Pellegrino, Paul M.

    2016-05-01

    The utility of peptide-based molecular sensing for the development of novel biosensors has resulted in a significant increase in their development and usage for sensing targets like chemical, biological, energetic and toxic materials. Using peptides as a molecular recognition element is particularly advantageous because there are several mature peptide synthesis protocols that already exist, peptide structures can be tailored, selected and manipulated to be highly discerning towards desired targets, peptides can be modified to be very stable in a host of environments and stable under many different conditions, and through the development of bifunctionalized peptides can be synthesized to also bind onto desired sensing platforms (various metal materials, glass, etc.). Two examples of the several Army relevant biological targets for peptide-based sensing platforms include Ricin and Abrin. Ricin and Abrin are alarming threats because both can be weaponized and there is no antidote for exposure. Combining the sensitivity of SERS with the selectivity of a bifunctional peptide allows for the emergence of dynamic hazard sensor for Army application.

  17. Comparison of amino acid v peptide based enteral diets in active Crohn's disease: clinical and nutritional outcome.

    PubMed Central

    Royall, D; Jeejeebhoy, K N; Baker, J P; Allard, J P; Habal, F M; Cunnane, S C; Greenberg, G R

    1994-01-01

    Elemental diets are considered an effective primary treatment for active Crohn's disease. This study examined the hypothesis that improvement occurs because of the presence of amino acids or the low fat content, or both. A randomised, controlled trial was undertaken in 40 patients with active Crohn's disease to evaluate clinical and nutritional outcomes after an amino acid based diet containing 3% fat was given by a feeding tube compared with a peptide based diet containing 33% fat. After three weeks' treatment, clinical remission occurred in 84% of patients who were given the amino acid diet and 75% of patients who received the peptide diet (p = 0.38). Plasma linoleic acid concentration was reduced after the amino acid but not the peptide diet. An increase in total body nitrogen was associated with the magnitude of nutritional depletion before treatment and at six months' follow up, only patients who showed gains in total body nitrogen after enteral nutrition had a sustained clinical remission. This study shows that peptide based high fat diets are as effective as amino acid low fat diets for achieving clinical remission in active Crohn's disease. Improved total body protein stores but not essential fatty acid depletion may be an important indicator of a sustained remission. PMID:8020806

  18. Challenges in developing a cross-serotype rhinovirus vaccine.

    PubMed

    Glanville, Nicholas; Johnston, Sebastian L

    2015-04-01

    A great burden of disease is attributable to human rhinovirus (HRV) infections which are the major cause of the common cold, exacerbations of both asthma and chronic obstructive pulmonary disease (COPD), and are associated with asthma development. Despite this there is currently no vaccine for HRV. The first vaccine studies showed some promise in terms of serotype-specific protection against cold symptoms, but antigenic heterogeneity amongst the >150 HRVs has been regarded as a major barrier to effective vaccine development and has resulted in little progress over 50 years. Here we review those vaccine studies conducted to date, discuss the difficulties posed by antigenic heterogeneity and describe some recent advances in generating cross-reactive antibodies and T cell responses using peptide immunogens. PMID:25829255

  19. Human Vaccines & Immunotherapeutics

    PubMed Central

    Riedmann, Eva M

    2013-01-01

    DNA vaccine for T1D promising in the clinic HPV vaccines halved infections in US teenage girls Modified DC immunotherapy against melanoma New study looks at clinical severity of human H7N9 infections Prevnar vaccines are valuable for healthcare systems GAPVAC: New consortium in the fight of brain cancer Cytomegalovirus vaccine to enter phase 3 Malaria vaccination using chemically attenuated parasites

  20. Fish Vaccines in Aquaculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccination is a proven, cost-effective method to prevent infectious diseases in animals. Current fish vaccines can be categorized as killed fish vaccines or modified live vaccines. The major advantage of live vaccine is their ability to stimulate both cell-mediated and humoral immune responses for ...

  1. Peptide-based allergen specific immunotherapy for the treatment of allergic disorders.

    PubMed

    El-Qutob, David; Reche, Pedro; Subiza, José L; Fernández-Caldas, Enrique

    2015-01-01

    Allergen specific immunotherapy (ASIT) and environmental control are the only etiologic treatments of allergic rhino-conjunctivitis, asthma and atopic dermatitis. The clinical benefit of ASIT relies on the selection of the patients and the identification and administration of the allergen, or allergens. Different routes of administration have been investigated, including subcutaneous, intradermal, epicutaneous, sublingual, inhaled, or intra-lymphatic. While subcutaneous and sublingual allergen specific immunotherapy may require from 3 to 5 years of treatment, clinical efficacy with intra-lymphatic treatment can be achieved after 3 injections. The most severe side effect of ASIT is anaphylaxis. Novel approaches are being investigated to reduce the allergenicity of immunotherapy vaccines, maintaining immunogenicity. Peptide immunotherapy has been directed mostly against autoimmune diseases, but the use of synthetic peptides for ASIT is a promising field in basic science, applied immunology and in clinical development. Short synthetic peptides bear allergen-specific CD4 T-cell epitopes which induce tolerance by stimulating regulatory (Treg) and Th1 cells. In the present patent review, we describe new trends in allergen immunotherapy using peptides, which, from a clinical point of view, are promising. PMID:25760734

  2. Influenza virus vaccine live intranasal--MedImmune vaccines: CAIV-T, influenza vaccine live intranasal.

    PubMed

    2003-01-01

    that it should be able to provide these data without conducting further clinical trials. In January 2002, Aviron submitted additional clinical and manufacturing data on FluMist to the US FDA. MedImmune received a second Complete Response Letter from the US FDA on 10 July 2002, requesting clarification and additional data relating to previously submitted information. One of the most significant issues raised by the US FDA was the exacerbated rate of asthma and wheezing in 18-35-month-old patients using FluMist. MedImmune is considering two options to address this issue; to either exclude patients with asthma and wheezing from the label, or to exclude 18- to 30-month-old patients from the proposed indication. On 26 August 2002, MedImmune reported that it had completed the submission of information requested by the US FDA for FluMist. On 17 December 2002, the US FDA's Vaccination and Related Biologicals Products Advisory Committee (VRBPAC) recommended that the FDA approve FluMist to prevent influenza in healthy children, adolescents and adults (ages 5-49 years). Even though the VRBPAC voted in favour of the product's safety in the 50- to 64-year age group, they believed that the data set on efficacy for this age group was insufficient. The committee has also recommended that head-to-head studies should be conducted comparing FluMist to the marketed trivalent inactivated vaccine. Additional clinical trials suggested by the VRBPAC were shedding studies to more clearly define the probability of transmitting the influenza vaccine virus to a high-risk patient and annual revaccination studies. On 30 January 2003, MedImmune announced that it had received a Complete Response Letter from the US FDA requesting clarification and additional information relating to data previously submitted. No additional clinical trials were requested. The company responded to the five questions contained in the letter on 7 February 2003. (ABSTRACT TRUNCATED) PMID:12952502

  3. Vaccine-Preventable Disease Photos

    MedlinePlus

    ... About | A-Z | Contact | Follow Vaccine Information You Need VACCINE BASICS Evaluating Online Health Information FAQs How Vaccines Work Importance of Vaccines Paying for Vaccines State Immunization Programs Tips for Finding Vaccine Records Trusted Sources of Vaccine ... PRETEENS Vaccines You Need ...

  4. Pneumococcal Polysaccharide Vaccine

    MedlinePlus

    Pneumococcal polysaccharide vaccine (PPSV)Treatment of pneumococcal infections with penicillin and other drugs used to be more effective. But ... the disease, through vaccination, even more important. Pneumococcal polysaccharide vaccine (PPSV) protects against 23 types of pneumococcal ...

  5. Childhood Vaccine Schedule

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues Childhood Vaccine Schedule Past Issues / Spring 2008 Table of Contents ... please turn Javascript on. When to Vaccinate What Vaccine Why Birth (or any age if not previously ...

  6. Vaccines Stop Illness

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Vaccines Stop Illness Past Issues / Spring 2008 Table of ... meningitis won't infect, cripple, or kill children. Vaccine Safety In light of recent questions about vaccine ...

  7. Your Baby's First Vaccines

    MedlinePlus

    ... Barcodes Related Link Vaccines & Immunizations Your Child's First Vaccines Format: Select one PDF [335 KB] RTF [260 ... child will get one or more of these vaccines today: DTaP Hib Hepatitis B Polio PCV13 Why ...

  8. Vaccines and Pregnancy

    MedlinePlus

    ... pregnancy, please see the MotherToBaby fact sheet Seasonal Influenza Vaccine (Flu Shot) during Pregnancy ( http: / / mothertobaby. org/ fact- sheets/ seasonal- influenza- vaccine- flu- shot- pregnancy/ pdf/ ). Nasal spray flu vaccines ...

  9. Vaccinations and HIV

    MedlinePlus

    ... Do not measure your viral load within 4 weeks of any vaccination. Flu shots have been studied ... live” vaccination in the past 2 or 3 weeks. Still, the “MMR” vaccine against measles, mumps and ...

  10. Varicella (Chickenpox) Vaccine

    MedlinePlus

    ... vaccine called MMRV, which contains both chickenpox and MMR vaccines, may be given instead of the two individual ... like rash (about 1 person in 20) than MMR and varicella vaccines given separately. Moderate Problems:Seizure (jerking or staring) ...

  11. Vaccines for Pregnant Women

    MedlinePlus

    ... virus (HBV) during pregnancy Vaccination and Pregnancy Resources, journal articles, more sources, etc., from Immunization Action Coalition Video: "Vaccines and Your Baby" (26:41 min) Vaccine Education Center, Children's Hospital of Philadelphia, November 2002 Also ...

  12. Vaccine refrigeration

    PubMed Central

    McColloster, Patrick J; Martin-de-Nicolas, Andres

    2014-01-01

    This commentary reviews recent changes in Centers for Disease Control (CDC) vaccine storage guidelines that were developed in response to an investigative report by the Office of the Inspector General. The use of temperature data loggers with probes residing in glycol vials is advised along with storing vaccines in pharmaceutical refrigerators. These refrigerators provide good thermal distribution but can warm to 8 °C in less than one hour after the power is discontinued. Consequently, electric grid instability influences appropriate refrigerator selection and the need for power back-up. System Average Interruption Duration Index (SAIDI) values quantify this instability and can be used to formulate region-specific guidelines. A novel aftermarket refrigerator regulator with a battery back-up power supply and microprocessor control system is also described. PMID:24442209

  13. Rotavirus Vaccine -- Questions and Answers

    MedlinePlus

    ... to these vaccines. The infant's immune response to influenza vaccine administered at the same time as rotavirus vaccine ... previously that an inactivated vaccine (e.g., inactivated influenza vaccine) may be administered either simultaneously or at any ...

  14. Subviral Particle as Vaccine and Vaccine Platform

    PubMed Central

    Tan, Ming; Jiang, Xi

    2014-01-01

    Recombinant subvirual particles retain similar antigenic features of their authentic viral capsids and thus have been applied as nonreplicating subunit vaccines against viral infection and illness. Additionally, the self-assembled, polyvalent subviral particles are excellent platforms to display foreign antigens for immune enhancement for vaccine development. These subviral particle-based vaccines are noninfectious and thus safer than the conventional live attenuated and inactivated vaccines. While several VLP vaccines are available in the markets, numerous others, including dual vaccines against more than one pathogen, are under clinical or preclinical development. This article provides an update of these efforts. PMID:24662314

  15. Human Vaccines & Immunotherapeutics

    PubMed Central

    Riedmann, Eva M

    2014-01-01

    Measles vaccination: Targeted and non-targeted benefits CDC reports: 2-dose regimen of chickenpox vaccine is a success Positive preliminary results from the CAPiTA study Seasonal flu vaccine associate with reduced stroke risk HPV vaccine shown to halve cervical abnormalities Global prize for mobile mast vaccine storage project Developmental pathway of potent HIV-neutralizing antibodies Burkholderia vaccine: US Dep of Defense collaborates with Bavarian Nordic

  16. Human Vaccines & Immunotherapeutics

    PubMed Central

    Riedmann, Eva M

    2014-01-01

    Efficacy and safety of first-ever Dengue vaccine candidate in Phase 3 Agenus‘ brain cancer vaccine doubles survival rate in GBM patients New study: Rotavirus vaccines dramatically cut hospitalization rates in US children Therapeutic vaccines – from heart disease to cancer Agenus‘ genital herpes vaccine significantly reduces viral burden in Phase 2 The latest on PaxVax‘ and Gotovax AB’s cholera vaccine candidates ACIP ponders recommendation for Prevnar use in seniors PMID:25424916

  17. Human Vaccines & Immunotherapeutics

    PubMed Central

    Riedmann, Eva M.

    2012-01-01

    Two therapeutic HPV vaccine candidates successful in phase 1 Flu shot may prevent heart attacks and stroke CDX-1401 combined with TLR agonist: Positive phase 1 results Three MRSA vaccines in early clincial trials Ovarian cancer vaccine candidate DPX-Survivac: Positive interim results from phase 1 Chinese biotech partnership brings first hepatitis E vaccine to the market Therapeutic vaccine for treatment of genital herpes enters phase 2 Visionary concept: Printable vaccines PMID:23817319

  18. Engineered human vaccines

    SciTech Connect

    Sandhu, J.S. . Div. of Immunology and Neurobiology)

    1994-01-01

    The limitations of human vaccines in use at present and the design requirements for a new generation of human vaccines are discussed. The progress in engineering of human vaccines for bacteria, viruses, parasites, and cancer is reviewed, and the data from human studies with the engineered vaccines are discussed, especially for cancer and AIDS vaccines. The final section of the review deals with the possible future developments in the field of engineered human vaccines and the requirement for effective new human adjuvants.

  19. Human Vaccines & Immunotherapeutics: News

    PubMed Central

    Riedmann, Eva M.

    2014-01-01

    Oncolytic immunotherapy reduces the size of melanoma tumors in phase 3 trial EV71 vaccine protects children against HFMD Influenza vaccination important for risk groups Bharat‘s rotavirus vaccine is safe and modestly efficacious Successfully avoiding the cold-chain for vaccines FDA approval for Stallergenes’ sublingual grass pollen allergy immunotherapy HPV vaccination campaign could change from three to two doses in the UK Valneva continues phase 2/3 trial of Pseudomonas aeruginosa vaccine PMID:25290656

  20. Cytocompatibility, antibacterial activity and biodegradability of self-assembling beta-hairpin peptide-based hydrogels for tissue regenerative applications

    NASA Astrophysics Data System (ADS)

    Salick, Daphne Ann

    Every year, millions of people suffer from tissue loss or failure. One approach to repair damaged or diseased tissue is through tissue/organ transplantation. However, one of the major problems which exist with this approach is that there are more people in need of a transplant than there are donors. Over the past several decades, scientists and doctors have come together to find a way to overcome this challenge. This collaboration has led to the development of biomimetic scaffolds, which closely mimic the desired tissue of interest to act as a substitute for the unfunctional tissue, with hopes to improve the quality of life. The Schneider and Pochan labs have developed a biomimetic scaffold using self-assembling beta-hairpin peptides. The self-assembly event can be triggered in response to physiological conditions, which is dictated by the monomer, to form non covalently crosslinked mechanically rigid hydrogels. In vitro studies showed that hydrogels were cytocompatible and may not elicit a pro-inflammatory response from murine macrophages. These material properties show promise for the use of these hydrogels in tissue engineering. When implanting a material into a host, a major concern is the introduction of infection. Infection, if not prevented or halted, results in poor tissue integration and function, ultimately leading to implant removal from the host. Interestingly, the beta-hairpin hydrogels were shown to exhibit antibacterial properties against pathogens commonly found in hospital environments. This inherently antibacterial hydrogel is advantageous because it may help decrease or diminish bacterial contamination when implanted in vivo, which may help to increase the success of implants. Also, a unique and exciting feature of these peptide-based hydrogels is their ability to shear-thin and self-heal. Hydrogels can be directly formed in a syringe and be subsequently delivered to a tissue defect in a minimally invasive manner where they will recover to their

  1. Vaccines.gov

    MedlinePlus

    ... Getting Vaccinated More Info Glossary Our Partners Related Websites AIDS.gov Biomedical Advanced Research and Development Authority (BARDA) CDC Vaccines Countermeasures Injury Compensation Program ...

  2. Vanishing vaccinations: why are so many Americans opting out of vaccinating their children?

    PubMed

    Calandrillo, Steve P

    2004-01-01

    Vaccinations against life-threatening diseases are one of the greatest public health achievements in history. Literally millions of premature deaths have been prevented, and countless more children have been saved from disfiguring illness. While vaccinations carry unavoidable risks, the medical, social and economic benefits they confer have led all fifty states to enact compulsory childhood vaccination laws to stop the spread of preventable diseases. Today, however, vaccines are becoming a victim of their success--many individuals have never witnessed the debilitating diseases that vaccines protect against, allowing complacency toward immunization requirements to build. Antivaccination sentiment is growing fast in the United States, in large part due to the controversial and hotly disputed link between immunizations and autism. The internet worsens fears regarding vaccination safety, as at least a dozen websites publish alarming information about the risks of vaccines. Increasing numbers of parents are refusing immunizations for their children and seeking legally sanctioned exemptions instead, apparently fearing vaccines more than the underlying diseases that they protect against. A variety of factors are at play: religious and philosophical beliefs, freedom and individualism, misinformation about risk, and overperception of risk. State legislatures and health departments now face a difficult challenge: respecting individual rights and freedoms while also safeguarding the public welfare. Nearly all states allow vaccination exemptions for religious reasons and a growing number provide "philosophical" opt-outs as well. However, in all but a handful of jurisdictions, neither objection is seriously documented or verified. Often, the law requires a parent to do no more than simply check a box indicating she does not wish her child to receive immunizations. The problem is exacerbated by financial incentives schools have to encourage students to opt out of vaccinations

  3. Strategies for Development of a Peptide Vaccine for Poultry Respiratory Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterial respiratory disease of turkeys causes millions of dollars in economic losses to the poultry industries. Poultry or avian respiratory disease complex may involve several pathogens both viral and bacterial, and disease is exacerbated by environmental stress. Live attenuated vaccines are avai...

  4. Paradoxical exacerbation of chronic plaque psoriasis by sorafenib.

    PubMed

    Yiu, Z Z N; Ali, F R; Griffiths, C E M

    2016-06-01

    Vascular endothelial growth factor (VEGF) antagonists have been investigated as a potential treatment for psoriasis, but there have been reports of VEGF antagonists triggering and/or exacerbating pre-existing psoriasis. We present the case of a 61-year old-man with exacerbation of pre-existing psoriasis after treatment with sorafenib, a small molecule inhibitor of the tyrosine kinase domain of the VEGF receptor, and we review the literature for other published cases of sorafenib-induced or sorafenib-exacerbated psoriasis. Clinicians, including both dermatologists and oncologists, should be aware of this potential side-effect of sorafenib in addition to the other cutaneous side effects reported for this drug. PMID:26667599

  5. Oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    Brill, Simon E; Wedzicha, Jadwiga A

    2014-01-01

    Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the history of this debilitating lung condition. Associated health care utilization and morbidity are high, and many patients require supplemental oxygen or ventilatory support. The last 2 decades have seen a substantial increase in our understanding of the best way to manage the respiratory failure suffered by many patients during this high-risk period. This review article examines the evidence underlying supplemental oxygen therapy during exacerbations of COPD. We first discuss the epidemiology and pathophysiology of respiratory failure in COPD during exacerbations. The rationale and evidence underlying oxygen therapy, including the risks when administered inappropriately, are then discussed, along with further strategies for ventilatory support. We also review current recommendations for best practice, including methods for improving oxygen provision in the future. PMID:25404854

  6. Simple, rapid detection of influenza A (H1N1) viruses using a highly sensitive peptide-based molecular beacon.

    PubMed

    Lim, Eun-Kyung; Guk, Kyeonghye; Kim, Hyeran; Chung, Bong-Hyun; Jung, Juyeon

    2016-01-01

    A peptide-based molecular beacon (PEP-MB) was prepared for the simple, rapid, and specific detection of H1N1 viruses using a fluorescence resonance energy transfer (FRET) system. The PEP-MB exhibited minimal fluorescence in its "closed" hairpin structure. However, in the presence of H1N1 viruses, the specific recognition of the hemagglutinin (HA) protein of H1 strains by the PEP-MB causes the beacon to assume an "open" structure that emits strong fluorescence. The PEP-MB could detect H1N1 viruses within 15 min or even 5 min and can exhibit strong fluorescence even at low viral concentrations, with a detection limit of 4 copies. PMID:26509476

  7. Immune functional impacts of oyster peptide-based enteral nutrition formula (OPENF) on mice: a pilot study

    NASA Astrophysics Data System (ADS)

    Cai, Bingna; Pan, Jianyu; Wu, Yuantao; Wan, Peng; Sun, Huili

    2013-07-01

    Oyster peptides were produced from Crassostrea hongkongensis and used as a new protein source for the preparation of an oyster peptide-based enteral nutrition formula (OPENF). Reserpineinduced malabsorption mice and cyclophosphamide-induced immunosuppression mice were used in this study. OPENF powder is light yellow green and has a protein-fat-carbohydrate ratio of 16:9:75 with good solubility in water. A pilot study investigating immune functional impacts of the OPENF on mice show that the OPENF enhanced spleen lymphocyte proliferation and the activity of natural killer (NK) cells in BALB/c mice. Furthermore, OPENF can improve intestinal absorption, increase food utilization ratio, and maintain the normal physiological function of mice. These results suggest that oyster peptides could serve as a new protein source for use in enteral nutrition formula, but more importantly, also indicate that OPENF has an immunostimulating effect in mice.

  8. Thiazolidinediones are associated with a reduced risk of COPD exacerbations

    PubMed Central

    Rinne, Seppo T; Liu, Chuan-Fen; Feemster, Laura C; Collins, Bridget F; Bryson, Christopher L; O’Riordan, Thomas G; Au, David H

    2015-01-01

    Background Thiazolidinediones (TZDs) are oral antihyperglycemic medications that are selective agonists to peroxisome proliferator-activated receptor gamma and have been shown to have potent anti-inflammatory effects in the lung. Objective The purpose of this study was to assess whether exposure to TZDs is associated with a decreased risk of chronic obstructive pulmonary disease (COPD) exacerbation. Methods A cohort study was performed by collecting data on all US veterans with diabetes and COPD who were prescribed oral antihyperglycemic medications during from period of October 1, 2005 to September 30, 2007. Patients who had two or more prescriptions for TZDs were compared with patients who had two or more prescriptions for an alternative oral anti-hyperglycemic medication. Multivariable negative binomial regression was performed with adjustment for potential confounding factors. The primary outcome was COPD exacerbations, including both inpatient and outpatient exacerbations. Results We identified 7,887 veterans who were exposed to TZD and 42,347 veterans who were exposed to non-TZD oral diabetes medications. COPD exacerbations occurred in 1,258 (16%) of the TZD group and 7,789 (18%) of the non-TZD group. In multivariable negative binomial regression, there was a significant reduction in the expected number of COPD exacerbations among patients who were exposed to TZDs with an incidence rate ratio of 0.86 (95% CI 0.81–0.92). Conclusion Exposure to TZDs was associated with a small but significant reduction in risk for COPD exacerbation among diabetic patients with COPD. PMID:26300638

  9. Oklahoma City bombing: exacerbation of symptoms in veterans with PTSD.

    PubMed

    Moyers, F

    1996-02-01

    Posttraumatic stress disorder (PTSD) develops following exposure to an extremely traumatic stressor and consists of reexperiencing, avoidance, and hyperarousal symptoms. Exposure to stimuli reminiscent of the original trauma often causes an exacerbation of symptoms. Models attempting to explain this phenomenon include classical conditioning, emotional network imagery, and memory consolidation. The recent bombing in Oklahoma City caused an exacerbation of symptoms in veterans from World War II, the Korean War, and Vietnam, ranging from images of combat to memories of being called "baby-killer." These various responses to identical stimuli might help to explain the importance of attached meaning to traumatic events. PMID:8904036

  10. Aspirin desensitization in aspirin-exacerbated respiratory disease.

    PubMed

    White, Andrew A; Stevenson, Donald D

    2013-05-01

    Although aspirin desensitization was discovered in 1922, it was not until 1979 that a therapeutic use for aspirin treatment, under the protection of desensitization, was discovered. In the last 33 years, details of aspirin treatment have been refined to the point where it is now recognized and accepted as a major therapeutic intervention in the treatment of aspirin-exacerbated respiratory disease, with therapeutic efficacy in approximately two-thirds of patients. It is only effective in patients who have aspirin-exacerbated respiratory disease and none of the other nonsteroidal anti-inflammatory drugs, despite their cross-reactive inhibition of cyclooxygenase-1, can effectively take the place of aspirin. PMID:23639709

  11. Avian influenza vaccines and vaccination for poultry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccines against avian influenza (AI) have had more limited use in poultry than vaccines against other poultry diseases such as Newcastle disease (ND) and infectious bronchitis, and have been used more commonly in the developing world. Over the past 40 years, AI vaccines have been primarily based o...

  12. History of vaccination

    PubMed Central

    Plotkin, Stanley

    2014-01-01

    Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before. PMID:25136134

  13. Hepatitis B Vaccination Protection

    MedlinePlus

    ... The hepatitis B vaccination is a non-infectious, vaccine prepared from recombinant yeast cultures, rather than human blood or plasma. There is no risk of contamination from other bloodborne pathogens nor is there any ... from the vaccine. The vaccine must be administered according to the ...

  14. Episodic Mood Changes Preceding an Exacerbation of Multiple Sclerosis

    PubMed Central

    Sharma, Priya; Morrow, Sarah A.; Owen, Richard J.

    2015-01-01

    Multiple sclerosis is a neurologic inflammatory disease that can manifest with psychiatric symptoms. Although depression is the most common psychiatric diagnosis in patients with multiple sclerosis, how depression develops is not fully understood. We present the case of an individual who displayed episodic mood changes preceding an exacerbation of multiple sclerosis symptoms. The clinical and research implications of this association are discussed. PMID:26835163

  15. Aminophylline Dosage In Asthma Exacerbations in Children: A Systematic Review

    PubMed Central

    2016-01-01

    Background Adequate asthma treatment of childhood exacerbations with IV aminophylline depends on appropriate dosage. Recommendations to aim for a target therapeutic range may be inappropriate as serum concentrations correlate poorly with clinical improvement. This review aims to evaluate the evidence for the optimum dosage strategy of intravenous aminophylline in children suffering an exacerbation of asthma. Methods A systematic review comparing dosage regimens of intravenous aminophylline in children suffering an exacerbation of asthma. Primary outcomes were time until resolution of symptoms, mortality and need for mechanical ventilation. Secondary outcomes were date until discharge criteria are met, actual discharge and adverse effects. Data sources CENTRAL, CINAHL, MEDLINE and Web of Science. Search performed in March 2016 Eligibility criteria Studies using intravenous aminophylline in children with an acute exacerbation of asthma which reported the dosage and clinical outcomes. Findings 14 RCTs were included. There is a poor relationship between the dosage administered to children and symptom resolution, length of stay or need for mechanical ventilation. This study is limited due to its use of indirect evidence. Conclusion The currently recommended dosage regimens may not represent the optimum safety and efficacy of intravenous aminophylline. There is a need to develop the evidence base correlating dosage with patient centered clinical outcomes, to improve prescribing practices. PMID:27483163

  16. Viral disruption of olfactory progenitors is exacerbated in allergic mice.

    PubMed

    Ueha, R; Mukherjee, S; Ueha, S; de Almeida Nagata, D E; Sakamoto, T; Kondo, K; Yamasoba, T; Lukacs, N W; Kunkel, S L

    2014-09-01

    Upper airway viral infection in patients with airway allergy often exacerbates olfactory dysfunction, but the mechanism for this exacerbation remains unclear. Here, we examined the effects of respiratory syncytial virus (RSV) infection, in the presence or absence of airway allergy, on olfactory receptor neurons (ORNs) and their progenitors in mice. Immunohistological analyses revealed that cockroach allergen (CRA)-induced airway allergy alone did not affect the number of OMP(+) mature ORNs and SOX2(+) ORN progenitors. Intranasal RSV line 19 infection in allergy-free mice resulted in a transient decrease in SOX2(+) ORN progenitors without affecting OMP(+) ORNs. In contrast, the RSV-induced decrease in SOX2(+) ORN progenitors was exacerbated and prolonged in allergic mice, which resulted in eventual loss of OMP(+) ORNs. In the allergic mice, reduction of RSV in the olfactory epithelium was delayed as compared with allergy-free mice. These results suggest that ORN progenitors were impaired by RSV infection and that airway allergy exacerbated damage to ORN progenitors by reducing viral clearance. PMID:24998164

  17. Mouse models of acute exacerbations of allergic asthma.

    PubMed

    Kumar, Rakesh K; Herbert, Cristan; Foster, Paul S

    2016-07-01

    Most of the healthcare costs associated with asthma relate to emergency department visits and hospitalizations because of acute exacerbations of underlying chronic disease. Development of appropriate animal models of acute exacerbations of asthma is a necessary prerequisite for understanding pathophysiological mechanisms and assessing potential novel therapeutic approaches. Most such models have been developed using mice. Relatively few mouse models attempt to simulate the acute-on-chronic disease that characterizes human asthma exacerbations. Instead, many reported models involve relatively short-term challenge with an antigen to which animals are sensitized, followed closely by an unrelated triggering agent, so are better described as models of potentiation of acute allergic inflammation. Triggers for experimental models of asthma exacerbations include (i) challenge with high levels of the sensitizing allergen (ii) infection by viruses or fungi, or challenge with components of these microorganisms (iii) exposure to environmental pollutants. In this review, we examine the strengths and weaknesses of published mouse models, their application for investigation of novel treatments and potential future developments. PMID:26922049

  18. Viruses in Idiopathic Pulmonary Fibrosis. Etiology and Exacerbation.

    PubMed

    Moore, Bethany B; Moore, Thomas A

    2015-11-01

    Viral infections are important contributors to exacerbation of asthma and chronic obstructive pulmonary disease; however, the role of viruses in the pathogenesis of idiopathic pulmonary fibrosis (IPF) is less clear. This likely reflects that fact that IPF acute exacerbations are defined clinically as "noninfectious," and little attention has been paid to the outcomes of patients with IPF with diagnosed infections. However, accumulating evidence suggests that infections (both bacterial and viral) may influence disease outcomes either as exacerbating agents or initiators of disease. Support for a viral role in disease initiation comes from studies demonstrating the presence of herpesviral DNA and epithelial cell stress in the lungs of asymptomatic relatives at risk for developing familial IPF. In addition, the number of studies that can associate viral (especially herpesviral) signatures in the lung with the development of IPF is steadily growing, and activated leukocyte signatures in patients with IPF provide further support for infectious processes driving IPF progression. Animal modeling has been used to better understand how a gamma herpesvirus infection can modulate the pathogenesis of lung fibrosis and has demonstrated that preceding infections appear to reprogram lung epithelial cells during latency to produce profibrotic factors, making the lung more susceptible to subsequent fibrotic insult, whereas exacerbations of existing fibrosis, or infections in susceptible hosts, involve active viral replication and are influenced by antiviral therapy. In addition, there is new evidence that bacterial burden in the lungs of patients with IPF may predict a poor prognosis. PMID:26595738

  19. How Clinical Diagnosis Might Exacerbate the Stigma of Mental Illness

    ERIC Educational Resources Information Center

    Corrigan, Patrick W.

    2007-01-01

    Stigma can greatly exacerbate the experience of mental illness. Diagnostic classification frequently used by clinical social workers may intensify this stigma by enhancing the public's sense of "groupness" and "differentness" when perceiving people with mental illness. The homogeneity assumed by stereotypes may lead mental health professionals and…

  20. Novel Human Rhinoviruses and Exacerbation of Asthma in Children1

    PubMed Central

    Khetsuriani, Nino; Lu, Xiaoyan; Teague, W. Gerald; Kazerouni, Neely; Anderson, Larry J.

    2008-01-01

    To determine links between human rhinoviruses (HRV) and asthma, we used data from a case–control study, March 2003–February 2004, among children with asthma. Molecular characterization identified several likely new HRVs and showed that association with asthma exacerbations was largely driven by HRV-A and a phylogenetically distinct clade of 8 strains, genogroup C. PMID:18976575

  1. Vaccines today, vaccines tomorrow: a perspective.

    PubMed

    Loucq, Christian

    2013-01-01

    Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts. PMID:23596584

  2. Vaccines today, vaccines tomorrow: a perspective

    PubMed Central

    2013-01-01

    Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts. PMID:23596584

  3. Human vaccines & immunotherapeutics: news.

    PubMed

    Riedmann, Eva M

    2013-07-01

    Recent advances in the development of immunotherapeutic mAbs for cancer New vaccine reduces malaria infection by 72% Bavarian Nordic's cancer immunotherapy shows promise in colorectal cancer Chinese HFMD vaccine shows high efficacy in Phase 3 Two-dose regimen of Merck's Gardasil looks effective Accelerating influenza vaccine development using synthetic biology A key role for gut microbes in vaccination Understanding of and attitudes towards vaccines: a study in teenagers. PMID:23863285

  4. Existing antiviral vaccines.

    PubMed

    Ravanfar, Parisa; Satyaprakash, Anita; Creed, Rosella; Mendoza, Natalia

    2009-01-01

    The innovation of vaccines has allowed for one of the greatest advancements in the history of public health. The first of the vaccines have been the antiviral vaccines, in particular the smallpox vaccine that was first developed by Edward Jenner in 1796. This article will review vaccination for the following viral diseases: measles, mumps, rubella, polio, hepatitis A, hepatitis B, influenza, rotavirus, rabies, monkeypox, smallpox, Japanese encephalitis, and yellow fever. PMID:19335723

  5. Countering Vaccine Hesitancy.

    PubMed

    Edwards, Kathryn M; Hackell, Jesse M

    2016-09-01

    Immunizations have led to a significant decrease in rates of vaccine-preventable diseases and have made a significant impact on the health of children. However, some parents express concerns about vaccine safety and the necessity of vaccines. The concerns of parents range from hesitancy about some immunizations to refusal of all vaccines. This clinical report provides information about addressing parental concerns about vaccination. PMID:27573088

  6. A respiratory syncytial virus (RSV) vaccine based on parainfluenza virus 5 (PIV5)

    PubMed Central

    Phan, Shannon I.; Chen, Zhenhai; Xu, Pei; Li, Zhuo; Gao, Xiudan; Foster, Stephanie L.; Teng, Michael N.; Tripp, Ralph A.; Sakamoto, Kaori; He, Biao

    2014-01-01

    Human respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease and hospitalizations in infants and young children. It also causes significant morbidity and mortality in elderly and immune compromised individuals. No licensed vaccine currently exists. Parainfluenza virus 5 (PIV5) is a paramyxovirus that causes no known human illness and has been used as a platform for vector-based vaccine development. To evaluate the efficacy of PIV5 as a RSV vaccine vector, we generated two recombinant PIV5 viruses - one expressing the fusion (F) protein and the other expressing the attachment glycoprotein (G) of RSV strain A2 (RSV A2). The vaccine strains were used separately for single-dose vaccinations in BALB/c mice. The results showed that both vaccines induced RSV antigen-specific antibody responses, with IgG2a/IgG1 ratios similar to those seen in wild-type RSV A2 infection. After challenging the vaccinated mice with RSV A2, histopathology of lung sections showed that the vaccines did not exacerbate lung lesions relative to RSV A2-immunized mice. Importantly, both F and G vaccines induced protective immunity. Therefore, PIV5 presents an attractive platform for vector-based vaccines against RSV infection. PMID:24717150

  7. Maturation of dendritic cells with lipopeptides that represent vaccine candidates for hepatitis C virus.

    PubMed

    Chua, Brendon Y; Healy, Anne; Cameron, Paul U; Stock, Owen; Rizkalla, Michael; Zeng, Weiguang; Torresi, Joseph; Brown, Lorena E; Fowler, Nina L; Gowans, Eric J; Jackson, David C

    2003-02-01

    The ability of antigens to elicit immune responses depends upon their initial recognition, uptake, processing and presentation by dendritic cells. This fact has been recognized by many workers and dendritic cells are now regarded as natural 'adjuvants' in the business of vaccine design. One way of persuading dendritic cells to become interested in foreign material is to decorate it with lipid moieties found in bacteria. This approach has been used in the context of synthetic peptide-based immunogens and depending on the nature of the epitopes included, can provide highly immunogenic structures capable of eliciting antibody or cytotoxic T cell responses. In this paper we describe the results of experiments in which the stimulatory effects of peptide-based vaccine candidates on human dendritic cells are examined. Our findings indicate that lipidated structures comprising vaccine target sequences of viral origin coupled to the synthetic lipid groups of bacteria are able to induce the maturation of dendritic cells, as measured by the expression of cell surface MHC class II molecules. PMID:12534949

  8. Typhoid fever vaccination strategies.

    PubMed

    Date, Kashmira A; Bentsi-Enchill, Adwoa; Marks, Florian; Fox, Kimberley

    2015-06-19

    Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control. PMID:25902360

  9. Clearance of depot vaccine SPIO-labeled antigen and substrate visualized using MRI.

    PubMed

    Brewer, Kimberly D; Lake, Kerry; Pelot, Nicole; Stanford, Marianne M; DeBay, Drew R; Penwell, Andrea; Weir, Genevieve M; Karkada, Mohan; Mansour, Marc; Bowen, Chris V

    2014-12-01

    Immunotherapies, including peptide-based vaccines, are a growing area of cancer research, and understanding their mechanism of action is crucial for their continued development and clinical application. Exploring the biodistribution of vaccine components may be key to understanding this action. This work used magnetic resonance imaging (MRI) to characterize the in vivo biodistribution of the antigen and oil substrate of the vaccine delivery system known as DepoVax(TM). DepoVax uses a novel adjuvanted lipid-in-oil based formulation to solubilise antigens and promote a depot effect. In this study, antigen or oil were tagged with superparamagnetic iron oxide (SPIO), making them visible on MR images. This enables tracking of individual vaccine components to determine changes in biodistribution. Mice were injected with SPIO-labeled antigen or SPIO-labeled oil, and imaged to examine clearance of labeled components from the vaccine site. The SPIO-antigen was steadily cleared, with nearly half cleared within two months post-vaccination. In contrast, the SPIO-oil remained relatively unchanged. The biodistribution of the SPIO-antigen component within the vaccine site was heterogeneous, indicating the presence of active clearance mechanisms, rather than passive diffusion or drainage. Mice injected with SPIO-antigen also showed MRI contrast for several weeks post-vaccination in the draining inguinal lymph node. These results indicate that MRI can visualize the in vivo longitudinal biodistribution of vaccine components. The sustained clearance is consistent with antigen up-take and trafficking by immune cells, leading to accumulation in the draining lymph node, which corresponds to the sustained immune responses and reduced tumor burden observed in vaccinated mice. PMID:25444822

  10. Obesity vaccines

    PubMed Central

    Monteiro, Mariana P

    2014-01-01

    Obesity is one of the largest and fastest growing public health problems in the world. Last century social changes have set an obesogenic milieu that calls for micro and macro environment interventions for disease prevention, while treatment is mandatory for individuals already obese. The cornerstone of overweight and obesity treatment is diet and physical exercise. However, many patients find lifestyle modifications difficult to comply and prone to failure in the long-term; therefore many patients consider anti-obesity drugs an important adjuvant if not a better alternative to behavioral approach or obesity surgery. Since the pharmacological options for obesity treatment remain quite limited, this is an exciting research area, with new treatment targets and strategies on the horizon. This review discusses the development of innovative therapeutic agents, focusing in energy homeostasis regulation and the use of molecular vaccines, targeting hormones such as somatostatin, GIP and ghrelin, to reduce body weight. PMID:24365968

  11. Rotavirus vaccine: a review.

    PubMed

    Kumar, Goel Manish; Arun, Kumar; Bilas, Jain Ram; Ruchi, Jain; Pardeep, Khanna; Pradeep, Siwach

    2012-12-01

    Worldwide, large proportion i.e., 37% of deaths due to diarrhea in young children is attributed to rotavirus. A monovalent P1A[8] G1 vaccine and a pentavalent bovine-human reassortant vaccine human rotavirus vaccine had shown good clinical efficacy without any increase in intussusception among vaccine recipients. WHO recommends that the first dose of rotavirus vaccine should be administered to infants up to age of 6-15 weeks irrespective of the prior history of rotavirus infection and the maximum age for administering the last dose of the vaccine should be 32 weeks. Booster doses are not recommended. The current update reviews the issues related to rotavirus vaccines and their usages like milestones in the development of rotavirus vaccines, concerns regarding their efficacy and cost-effectiveness, immunity after natural infection, potential for changes in virus strains, current recommendations, post marketing surveillance, and future challenges and scope for further research regarding rotavirus vaccines. PMID:25145068

  12. [Developments in HPV vaccination].

    PubMed

    de Melker, Hester; Kenter, Gemma; van Rossum, Tekla; Conyn-van Spaendonck, Marina

    2012-01-01

    Vaccination against the human papilloma virus (HPV) has been included in the national Vaccination Programme of the Netherlands for 12-year-old girls since 2010. Vaccination coverage for the birth cohort of 1997 was 56.; there is a gradual increase in uptake. Continuous safety monitoring brought no new unknown serious side effects to light; many girls suffered from transient symptoms such as painful arm, fatigue and headache. After the current vaccines that protect against HPV types 2 and 4 types, respectively and induce some cross protection, vaccines are being developed that can induce broader protection. HPV vaccination of 12-year-old girls is cost-effective, even for relatively low vaccination coverage. The potential protection of HPV vaccination extends beyond prevention of cervical cancer by preventing other oncological manifestations of HPV infection in women as well as men and genital warts. The preventive HPV vaccines do not appear to be effective in treating existing abnormalities. PMID:23171565

  13. Current Vaccine Shortages and Delays

    MedlinePlus

    ... Patient Education Programs and Tools VTrckS (Vaccine Tracking System) Immunization Registries (IIS) Vaccines for Children (VFC) Stop Transmission of Polio (STOP) Vaccine Management Business Improvement Project (VMBIP) Global Immunizations & Vaccinations Immunization Program ...

  14. Mumps - Vaccine Q and A

    MedlinePlus

    ... containing vaccine, given as combination measles, mumps, rubella (MMR) vaccine, separated by at least 28 days, are routinely ... been vaccinated should also receive 1 dose of MMR vaccine, but adults who work in healthcare, a school/ ...

  15. Vaccinations for Adults with Diabetes

    MedlinePlus

    Vaccinations for Adults with Diabetes The table below shows which vaccinations you should have to protect your health if ... sure you and your healthcare provider keep your vaccinations up to date. Vaccine Do you need it? ...

  16. Side Effects of Smallpox Vaccination

    MedlinePlus

    ... Index SMALLPOX FACT SHEET Side Effects of Smallpox Vaccination The smallpox vaccine prevents smallpox. For most people, ... go away without treatment: The arm receiving the vaccination may be sore and red where the vaccine ...

  17. Vaccination: An Act of Love

    MedlinePlus

    ... benefits of vaccines. For this reason, we created Vaccination Week in the Americas to get vaccines to ... and no one gets left behind. Help the vaccination teams when they come to your town, your ...

  18. Human Papillomavirus (HPV) Vaccine (Gardasil)

    MedlinePlus

    ... changes or ringing in the ears.Like all vaccines, HPV vaccines will continue to be monitored for unusual ... visit CDC's website at http://www.cdc.gov/vaccines. HPV Vaccine (Gardasil) Information Statement. U.S. Department of Health ...

  19. Human Papillomavirus (HPV) Vaccine (Cervarix)

    MedlinePlus

    ... changes or ringing in the ears. Like all vaccines, HPV vaccines will continue to be monitored for unusual ... gov/std/hpv and http://www.cdc.gov/vaccines HPV Vaccine (Cervarix) Information Statement. U.S. Department of Health ...

  20. Vaccines against poverty

    PubMed Central

    MacLennan, Calman A.; Saul, Allan

    2014-01-01

    With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented. PMID:25136089

  1. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  2. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  3. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  4. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  5. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  6. 75 FR 48712 - Proposed Vaccine Information Materials for Influenza Vaccine

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-11

    ... season, 2009 H1N1 influenza vaccine is being incorporated into the seasonal vaccine formulation... vaccine provides some protection. The 2010-2011 vaccine provides protection against H1N1 (pandemic.... People who got the 2009 H1N1 vaccine still need to get vaccinated with the 2010-2011 influenza...

  7. Genetic variation in BAFF and asthma exacerbations among African American individuals

    PubMed Central

    Kumar, Rajesh; Williams, L. Keoki; Kato, Atsushi; Peterson, Edward L.; Favoreto, Silvio; Hulse, Katie; Wang, Deli; Beckman, Kenneth; Thyne, Shannon; LeNoir, Michael; Meade, Kelley; Lanfear, David E.; Levin, Albert M.; Favro, David; Yang, James J.; Weiss, Kevin; Boushey, Homer A.; Grammer, Leslie; Avila, Pedro C; Burchard, Esteban G.; Schleimer, Robert

    2012-01-01

    Capsule Summary A BAFF polymorphism is associated with asthma exacerbations and serum BAFF levels. BAFF expression in vivo increases in natural rhinovirus infection. BAFF may play a role in airway antiviral immunity and impact asthma exacerbation rates. PMID:22728080

  8. A potential therapeutic peptide-based neutralizer that potently inhibits Shiga toxin 2 in vitro and in vivo

    PubMed Central

    Li, Tao; Tu, Wei; Liu, Yuenan; Zhou, Peng; Cai, Kun; Li, Zhan; Liu, Xiong; Ning, Nianzhi; Huang, Jie; Wang, Shenghan; Huang, Jian; Wang, Hui

    2016-01-01

    Shiga toxin 2 (Stx2) is a major virulence factor in infections with Stx-producing Escherichia coli (STEC), which can cause serious clinical complications in humans, such as hemolytic uremic syndrome (HUS). Recently, we screened and identified two peptide-based Stx2 neutralizers, TF-1 and WA-8, which specifically and directly bind to Stx2. Computer simulations suggested that the majority of TF-1 or WA-8 binds tightly at the receptor-binding site 3 of Stx2. The two peptides also effectively inhibited the cytotoxic activity of Stx2 by blocking the binding of Stx2 to target cells. TF-1 exhibits remarkable therapeutic potency in both mice and rat toxicity models. In mice toxicity models, TF-1 provided full protection when mice were injected with 5 LD50 of Stx2. In rat toxicity models, TF-1 reduced fatal tissue damage and completely protected rats from the lethal challenges of Stx2. In these rats, TF-1 significantly decreased the concentration of Stx2 in blood and diminished tissue distribution levels of Stx2. Furthermore, TF-1 effectively protected rats from the pathological effects caused by Stx2, especially in the kidney, thymus, adrenal gland, and lung. Taken together, these results indicate that TF-1 is a promising therapeutic agent against the pathogenicity of Stx2. PMID:26903273

  9. A potential therapeutic peptide-based neutralizer that potently inhibits Shiga toxin 2 in vitro and in vivo.

    PubMed

    Li, Tao; Tu, Wei; Liu, Yuenan; Zhou, Peng; Cai, Kun; Li, Zhan; Liu, Xiong; Ning, Nianzhi; Huang, Jie; Wang, Shenghan; Huang, Jian; Wang, Hui

    2016-01-01

    Shiga toxin 2 (Stx2) is a major virulence factor in infections with Stx-producing Escherichia coli (STEC), which can cause serious clinical complications in humans, such as hemolytic uremic syndrome (HUS). Recently, we screened and identified two peptide-based Stx2 neutralizers, TF-1 and WA-8, which specifically and directly bind to Stx2. Computer simulations suggested that the majority of TF-1 or WA-8 binds tightly at the receptor-binding site 3 of Stx2. The two peptides also effectively inhibited the cytotoxic activity of Stx2 by blocking the binding of Stx2 to target cells. TF-1 exhibits remarkable therapeutic potency in both mice and rat toxicity models. In mice toxicity models, TF-1 provided full protection when mice were injected with 5 LD50 of Stx2. In rat toxicity models, TF-1 reduced fatal tissue damage and completely protected rats from the lethal challenges of Stx2. In these rats, TF-1 significantly decreased the concentration of Stx2 in blood and diminished tissue distribution levels of Stx2. Furthermore, TF-1 effectively protected rats from the pathological effects caused by Stx2, especially in the kidney, thymus, adrenal gland, and lung. Taken together, these results indicate that TF-1 is a promising therapeutic agent against the pathogenicity of Stx2. PMID:26903273

  10. Iterative design of peptide-based hydrogels and the effect of network electrostatics on primary chondrocyte behavior

    PubMed Central

    Sinthuvanich, Chomdao; Haines-Butterick, Lisa A.; Nagy, Katelyn J.; Schneider, Joel P.

    2012-01-01

    Iterative peptide design was used to generate two peptide-based hydrogels to study the effect of network electrostatics on primary chondrocyte behavior. MAX8 and HLT2 peptides have formal charge states of +7 and +5 per monomer, respectively. These peptides undergo triggered folding and self-assembly to afford hydrogel networks having similar rheological behavior and local network morphologies, yet different electrostatic character. Each gel can be used to directly encapsulate and syringe-deliver cells. The influence of network electrostatics on cell viability after encapsulation and delivery, extracellular matrix deposition, gene expression, and the bulk mechanical properties of the gel-cell constructs as a function of culture time was assessed. The less electropositive HLT2 gel provides a microenvironment more conducive to chondrocyte encapsulation, delivery, and phenotype maintenance. Cell viability was higher for this gel and although a moderate number of cells dedifferentiated to a fibroblast-like phenotype, many retained their chondrocytic behavior. As a result, gel-cell constructs prepared with HLT2, cultured under static in vitro conditions, contained more GAG and type II collagen resulting in mechanically superior constructs. Chondrocytes delivered in the more electropositive MAX8 gel experienced a greater degree of cell death during encapsulation and delivery and the remaining viable cells were less prone to maintain their phenotype. As a result, MAX8 gel-cell constructs had fewer cells, of which a limited number were capable of laying down cartilage-specific ECM. PMID:22841922

  11. The development of peptide-based interfacial biomaterials for generating biological functionality on the surface of bioinert materials

    PubMed Central

    Meyers, Steven R.; Khoo, Xiaojuan; Huang, Xin; Walsh, Elisabeth B.; Grinstaff, Mark W.; Kenan, Daniel J.

    2013-01-01

    Biomaterials used in implants have traditionally been selected based on their mechanical properties, chemical stability, and biocompatibility. However, the durability and clinical efficacy of implantable biomedical devices remains limited in part due to the absence of appropriate biological interactions at the implant interface and the lack of integration into adjacent tissues. Herein, we describe a robust peptide-based coating technology capable of modifying the surface of existing biomaterials and medical devices through the non-covalent binding of modular biofunctional peptides. These peptides contain at least one material binding sequence and at least one biologically active sequence and thus are termed, “Interfacial Biomaterials” (IFBMs). IFBMs can simultaneously bind the biomaterial surface while endowing it with desired biological functionalities at the interface between the material and biological realms. We demonstrate the capabilities of model IFBMs to convert native polystyrene, a bioinert surface, into a bioactive surface that can support a range of cell activities. We further distinguish between simple cell attachment with insufficient integrin interactions, which in some cases can adversely impact downstream biology, versus biologically appropriate adhesion, cell spreading, and cell survival mediated by IFBMs. Moreover, we show that we can use the coating technology to create spatially resolved patterns of fluorophores and cells on substrates and that these patterns retain their borders in culture. PMID:18929406

  12. Use of Multiple Peptide-Based SERS Probes Binding to Different Epitopes on a Protein Biomarker To Improve Detection Sensitivity.

    PubMed

    Shin, Kayeong; Cho, Jun-Haeng; Yoon, Moon-Young; Chung, Hoeil

    2016-04-01

    We propose an analytical strategy to improve the sensitivity for detecting a protein biomarker through signal multiplication by manipulating multiple peptide-based surface-enhanced Raman scattering (SERS) probes to bind the biomarker. Protective antigen (PA) was used as an Anthrax biomarker in this study. For this purpose, five small peptides selective to various PA epitopes with different binding affinities were chosen and peptide-conjugated Au nanoparticle (AuNP) SERS probes were individually prepared using each peptide. Initially, five different SERS probes were separately used to detect PA and the sensitivities were compared. Next, the possibility of enhancing sensitivity by employing multiple SERS probes was examined. Rather than applying the probes simultaneously, which would induce competitive binding, each probe was added sequentially and an optimal probe-addition sequence was determined to provide maximal sensitivity. Finally, PA samples at seven different concentrations were measured with the optimal sequence. The limit of detection (LOD) was 0.1 aM, and the enhancement was more effective at lower PA concentrations. The proposed scheme can be further applicable to detect other protein biomarkers to diagnose various diseases. PMID:26948277

  13. Using MRI to evaluate and predict therapeutic success from depot-based cancer vaccines

    PubMed Central

    DeBay, Drew R; Brewer, Kimberly D; LeBlanc, Sarah A; Weir, Genevieve M; Stanford, Marianne M; Mansour, Marc; Bowen, Chris V

    2015-01-01

    In the preclinical development of immunotherapy candidates, understanding the mechanism of action and determining biomarkers that accurately characterize the induced host immune responses is critical to improving their clinical interpretation. Magnetic resonance imaging (MRI) was used to evaluate in vivo changes in lymph node size in response to a peptide-based cancer vaccine therapy, formulated using DepoVax (DPX). DPX is a novel adjuvant lipid-in-oil–based formulation that facilitates enhanced immune responses by retaining antigens at the injection site for extended latencies, promoting increased potentiation of immune cells. C57BL/6 mice were implanted with C3 (HPV) tumor cells and received either DPX or control treatments, 5 days post-implantation. Complete tumor eradication occurred in DPX-vaccinated animals and large volumetric increases were observed in the vaccine-draining right inguinal lymph node (VRILN) in DPX mice, likely corresponding to increased localized immune response to the vaccine. Upon evaluating the relative measure of vaccine-potentiated immune activation to tumor-induced immune response (VRILN/VLILN), receiver-operating characteristic (ROC) curves revealed an area under the curve (AUC) of 0.90 (±0.07), indicating high specificity and sensitivity as a predictive biomarker of vaccine efficacy. We have determined that for this tumor model, early MRI lymph node volumetric changes are predictive of depot immunotherapeutic success. PMID:26730395

  14. Pemphigus foliaceus exacerbated by radiation, in association with myasthenia gravis.

    PubMed

    Liebman, Tracey N; Lieberman, Miriam R; Burris, Katy

    2016-01-01

    Pemphigus foliaceus (PF) is a sporadic autoimmune blistering disease of unknown etiology. The production of immunoglobulin G4 antibodies against desmoglein-1 is responsible for the clinical manifestation of PF. We present a case of a woman with a recent diagnosis of myasthenia gravis (MG), who was also recently treated with radiation therapy for breast cancer. The clinical exam, supported by biopsy and direct immunofluorescence, were consistent with PF. We present this case to increase the awareness of the potential exacerbation or induction of PF with radiation, and of the association of PF and myasthenia gravis. Only five prior cases of radiation-exacerbated or radiation-induced PF have been reported in the literature to date. Furthermore, the co-existence of the autoimmune entities of myasthenia gravis and PF has been reported in the literature in only 9 cases and was also noted in this patient. PMID:27136623

  15. Reduction of exacerbation frequency in patients with COPD after participation in a comprehensive pulmonary rehabilitation program

    PubMed Central

    van Ranst, D; Stoop, WA; Meijer, JW; Otten, HJ; van de Port, IG

    2014-01-01

    Background Pulmonary rehabilitation (PR) is an important treatment option for chronic obstructive pulmonary disease (COPD) patients and might contribute to a reduction in exacerbation and exacerbation-related hospitalization rate. Methods In this prospective study, all COPD patients that completed a comprehensive pulmonary rehabilitation program (PRP) between June 2006 and December 2012 were included. Self-reported exacerbation and hospitalization frequency 1 year before PR was retrospectively recorded. During the year following PR, exacerbation and hospitalization frequency was recorded with questionnaires. Results For 343 patients, complete information on exacerbation and hospitalization rate was obtained. The mean number of exacerbations decreased significantly after participating in a PRP by 1.37 exacerbations/year (95% confidence interval 1.029 to 1.717) from 4.56±3.26 exacerbations in the year preceding PR to 3.18±2.53 in the year following PR (P<0.0005). The number of hospitalizations due to exacerbations decreased significantly by 0.68 hospitalizations/year (95% confidence interval 0.467 to 0.903) from 1.48±1.84 in the year preceding PR to 0.80±1.31 hospitalizations/year in the year following PR (P<0.0005). The proportion of patients with a frequent exacerbation type (more than two exacerbations/year) was reduced by 24%. Multivariate regression analysis to explore determinants that might predict reduction in exacerbation frequency or change in exacerbation pattern did not reveal clinically useful predictors, although patients with more exacerbations before PR had the highest potential for reduction. Conclusion In a large population of severely impaired COPD patients with high exacerbation rates, a significant reduction in exacerbation and hospitalization frequency was observed after participation in a comprehensive PRP. PMID:25336938

  16. HIV/AIDS and Vaccines

    MedlinePlus

    ... Prevention Research : Vaccines Subscribe Translate Text Size Print Vaccines What Are Vaccines and What Do They Do? A vaccine—also ... immune response against the disease. Is There a Vaccine for HIV? No. There is currently no vaccine ...

  17. Effects of N-acetylcysteine on asthma exacerbation.

    PubMed

    Aliyali, Masoud; Poorhasan Amiri, Ali; Sharifpoor, Ali; Zalli, Fatemeh

    2010-06-01

    Airway mucus hypersecretion and increased oxidative stress are clinical and pathophysiological features of asthma exacerbation. We studied effects of N-acetylcysteine (NAC) as a mucolytic and antioxidant agent in asthma exacerbation. In this randomized, single-blinded, placebo-controlled study 50 patients ( 17 male, 33 female, mean age 48.94+/-13.68) with asthma exacerbation were randomized to receive either oral 600 mg b.d. N-acetylcysteine or placebo in addition to standard treatment during 5 days hospitalization. Daily measurements of wheezing, dyspnea, cough, sputum, expectoration, night sleep scores and morning PEFR were performed. There was no significant difference in wheezing score between patients assigned NAC and those assigned placebo in day 5(0.84[SD 0.94] VS 0.87[SD 0.79]) and also in cough score (0.72[SD 0.84] VS 0.79[SD 0.97]), dyspnea score (0.84[SD 1.06] VS 0.91[SD 1.01]), sputum score(0.79[SD 0.83] VS 0.62[SD 0.71]), expectoration score(0.79[SD 0.97] VS 0.83[SD 1.09]), night sleep score(1[SD 1.17] VS 0.67[SD 0.98] and morning PEFR (256[SD 96.36] VS 282[SD 98.86]). We concluded that addition of N-acetylcysteine to usual asthma medication has no significant effect in treatment of asthma exacerbation. PMID:20683104

  18. Intranasal substituted cathinone "bath salts" psychosis potentially exacerbated by diphenhydramine.

    PubMed

    Gunderson, Erik W; Kirkpatrick, Matthew G; Willing, Laura M; Holstege, Christopher P

    2013-01-01

    In this report, we describe a case of intranasal "bath salts"-associated psychosis. Symptoms developed during a 3-week binge and were potentially exacerbated by oral diphenhydramine taken for insomnia. The clinical case conference includes expert discussion from 3 disciplines: emergency medicine toxicology, behavioral pharmacology, and addiction medicine. It is hoped that the discussion will provide insight into the clinical aspects and challenges of addressing acute substituted cathinone toxicity, including acute psychosis, a major adverse effect of bath salts consumption. PMID:23732955

  19. Chronic Rhinosinusitis and Aspirin-Exacerbated Respiratory Disease.

    PubMed

    Dunn, Neha M; Katial, Rohit K

    2016-08-01

    Patients with severe asthma and concomitant chronic rhinosinusitis often have severe, refractory upper and lower airway inflammation. This inflammation has been proposed to be similar throughout the upper and lower airways leading to the unified airways concept. This article reviews chronic rhinosinusitis with and without nasal polyps, and the subgroup with aspirin-exacerbated respiratory disease, while focusing on the relationship with asthma. Additionally, diagnosis and treatment with current and newer therapies are discussed. PMID:27401622

  20. Progression of female reproductive stages associated with bipolar illness exacerbation

    PubMed Central

    Marsh, Wendy K.; Ketter, Terence A.; Crawford, Sybil L.; Johnson, Julia V.; Kroll-Desrosiers, Aimee; Rothschild, Anthony J.

    2012-01-01

    Objectives Late perimenopause and early postmenopause confer an increased risk of depression in the population, yet bipolar disorder mood course during these times remains unclear. Methods Clinic visits in 519 premenopausal, 116 perimenopausal including 13 women transitioning from perimenopause to postmenopause, and 133 postmenopausal women with bipolar disorder who received naturalistic treatment in the multisite STEP-BD study over 19.8±15.5 months were analyzed for mood state. History of postpartum and perimenstrual mood exacerbation and current hormone therapy were evaluated as potential mood predictors. Results A progression in female reproductive stage (premenopause, perimenopause, and postmenopausae) was significantly associated with percent of visits decreasing in euthymia (29.3%, 27.0%, 25.0%, respectively, p<0.05) decreasing in syndromal mood elevation (5.3%, 4.1%, and 3.0%, respectively, p<0.001), and increasing in subsyndromal symptoms (47.3%, 50.7%, and 52.7%, respectively, p = 0.05). Thirteen women transitioning from peri- to postmenopause had a significantly greater proportion of visits in syndromal depression (24.4%, p<0.0005) compared to premenopausal, perimenopausal and postmenopausal women, while depression in the latter three groups (18.1%, 18.1%, and 19.3%, respectively) did not differ. Perimenstrual and/or postpartum mood exacerbation, or hormone therapy did not significantly alter depression during perimenopause. Conclusions A progression in female reproductive stages was associated with bipolar illness exacerbation. A small number of women transitioning from perimenopause to postmenopause had significantly greater depression than other female reproductive groups. Euthymia and mood elevation decreased with progressing female reproductive stage. Menstrual cycle or postpartum mood exacerbation, or current hormone therapy use, was not associated with perimenopausal depression. Future studies, which include hormonal assessments, are needed to

  1. Infection as an Environmental Trigger of Multiple Sclerosis Disease Exacerbation.

    PubMed

    Steelman, Andrew J

    2015-01-01

    Over the past several decades, significant advances have been made in identifying factors that contribute to the pathogenesis of multiple sclerosis (MS) and have culminated in the approval of some effective therapeutic strategies for disease intervention. However, the mechanisms by which environmental factors, such as infection, contribute to the pathogenesis and/or symptom exacerbation remain to be fully elucidated. Relapse frequency in MS patients contributes to neurological impairment and, in the initial phases of disease, serves as a predictor of poor disease prognosis. The purpose of this review is to examine the evidence that supports a role for peripheral infection in modulating the natural history of this disease. Evidence supporting a role for infection in promoting exacerbation in animal models of MS is also reviewed. Finally, a few mechanisms by which infection may exacerbate symptoms of MS and other neurological diseases are discussed. Those who comprise the majority of MS patients acquire approximately two upper-respiratory infections per year; furthermore, this type of infection doubles the risk for MS relapse, underscoring the contribution of this relationship as being potentially important and particularly detrimental. PMID:26539193

  2. Infection as an Environmental Trigger of Multiple Sclerosis Disease Exacerbation

    PubMed Central

    Steelman, Andrew J.

    2015-01-01

    Over the past several decades, significant advances have been made in identifying factors that contribute to the pathogenesis of multiple sclerosis (MS) and have culminated in the approval of some effective therapeutic strategies for disease intervention. However, the mechanisms by which environmental factors, such as infection, contribute to the pathogenesis and/or symptom exacerbation remain to be fully elucidated. Relapse frequency in MS patients contributes to neurological impairment and, in the initial phases of disease, serves as a predictor of poor disease prognosis. The purpose of this review is to examine the evidence that supports a role for peripheral infection in modulating the natural history of this disease. Evidence supporting a role for infection in promoting exacerbation in animal models of MS is also reviewed. Finally, a few mechanisms by which infection may exacerbate symptoms of MS and other neurological diseases are discussed. Those who comprise the majority of MS patients acquire approximately two upper-respiratory infections per year; furthermore, this type of infection doubles the risk for MS relapse, underscoring the contribution of this relationship as being potentially important and particularly detrimental. PMID:26539193

  3. Independent effect of prior exacerbation frequency and disease severity on the risk of future exacerbations of COPD: a retrospective cohort study.

    PubMed

    Margüello, Miguel Santibañez; Garrastazu, Roberto; Ruiz-Nuñez, Mario; Helguera, Jose Manuel; Arenal, Sandra; Bonnardeux, Cristina; León, Carlos; Miravitlles, Marc; García-Rivero, Juan Luis

    2016-01-01

    Few studies have researched the independent effect of COPD severity on the risk of future exacerbations adjusted by previous exacerbation frequency. We aimed to analyse the independent effect of COPD severity on the risk of exacerbations in the following year, and whether this effect was stronger or not than the effect of a previous history of exacerbations. We conducted a retrospective population-based cohort study including 900 patients with confirmed COPD. Exacerbation frequency was observed for the previous year and for the following year. Patients were defined as 'Frequent Exacerbator' (FE) phenotype if they suffered ⩾2 exacerbations in a year, and were categorised according to the severity of COPD (GOLD Grades 1-4). Odds ratios (ORs) were estimated by logistic regression adjusting for age, gender, smoking status, severity of COPD and being FE in the previous year. The main predictor of being FE among all grades of COPD severity was a history of frequent exacerbations in the previous year: adjusted OR 4.97; 95% confidence interval (CI) (3.54-6.97). COPD severity was associated with a higher risk of being FE: Crude OR GOLD Grade 4 3.86; 95% CI (1.50-9.93). However, this association diminished after adjusting for being FE in the previous year: adjusted OR 2.08; 95% CI (0.75-5.82). Our results support that a history of frequent exacerbations in the previous year is the most important independent predictor of exacerbations in the following year, also among the most severe COPD patients. Severity of COPD would be associated with a higher risk of exacerbations, but this effect would be partly determined by the exacerbations suffered in the previous year. PMID:27604472

  4. MMR Vaccine (Measles, Mumps, and Rubella)

    MedlinePlus

    Attenuvax® Measles Vaccine ... R-Vax® II (as a combination product containing Measles Vaccine, Rubella Vaccine) ... M-R® II (as a combination product containing Measles Vaccine, Mumps Vaccine, Rubella Vaccine)

  5. The HPV Vaccination Crisis

    Cancer.gov

    Following the release of a consensus statement from the NCI-Designated Cancer Centers urging HPV vaccination in the United States, Dr. Noel Brewer discusses the country’s low vaccination rates and how clinicians can help to improve them.

  6. Pneumococcal Vaccines (PCV, PPSV)

    MedlinePlus

    ... Know About Zika & Pregnancy Your Child's Immunizations: Pneumococcal Vaccines (PCV, PPSV) KidsHealth > For Parents > Your Child's Immunizations: ... or HIV infection); or cochlear implants. Why the Vaccines Are Recommended Children younger than 2 years old, ...

  7. Screening Tests and Vaccines

    MedlinePlus

    ... Contact Us Text size | Print | Screening Tests and Vaccines This information in Spanish ( en español ) Getting important screening tests and vaccines can save your life. Check this section of ...

  8. [Biotechnology and vaccinations].

    PubMed

    Peret, R

    1990-12-01

    Current biotechnologies used in the manufacture of new vaccines are of three kinds: Genetic recombinations leading to either vaccinal sub-units or living vaccines represented by recombinant vectors; Chemical synthesis techniques; Use of the spatial configuration of an anti-antibody similar to the initial antigen. These are the anti-idiotype vaccines. Genetic engineering is the basis of a new generation of vaccines, sought with the aim of attempting to eradicate a number of diseases throughout the world. However, there is presently an inadequacy in resources, most often linked to financial considerations, which limits widespread systematic vaccination. In the future, vaccines against dental caries will probably be obtained from purified proteins of hydrolase fractions common to cariogenic bacteria and resulting from genetic recombinations in the form of vaccinal sub-units. PMID:2077866

  9. Smallpox Vaccine Overview

    MedlinePlus

    ... complications from the vaccinia virus can be severe. Benefit of Vaccine Following Exposure Vaccination within 3 days ... Policies About CDC.gov Link to Us All Languages Contact CDC Centers for Disease Control and Prevention ...

  10. Hepatitis B Vaccine

    MedlinePlus

    ... as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... What is hepatitis B?Hepatitis B is a serious infection that affects the liver. It is caused by the hepatitis B virus. ...

  11. Tetanus (Lockjaw) Vaccination

    MedlinePlus

    ... adults - Tetanus-diphtheria-acellular Pertussis vaccine Tetanus (Lockjaw) Vaccination Recommend on Facebook Tweet Share Compartir Tetanus (lockjaw) ... Related Pages Diphtheria Pertussis Feature Story: Adults Need Immunizations, Too Also Known As & Abbreviations Tetanus = Lockjaw DTaP = ...

  12. Meningococcal Vaccine (For Parents)

    MedlinePlus

    ... Things to Know About Zika & Pregnancy Your Child's Immunizations: Meningococcal Vaccines KidsHealth > For Parents > Your Child's Immunizations: ... are at increased risk of developing meningococcal disease. Immunization Schedule Vaccination with MCV4 is recommended: when kids ...

  13. Hepatitis A Vaccine

    MedlinePlus

    Twinrix® (as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... What is hepatitis A?Hepatitis A is a serious liver disease caused by the hepatitis A virus (HAV). HAV is found in ...

  14. Your child's first vaccines

    MedlinePlus

    ... these vaccines today: [ ] DTaP [ ] Hib [ ] Hepatitis B [ ] Polio [ ] PCV13 (Provider: Check appropriate boxes) 1. Why get vaccinated? ... the 6-month dose is not needed. Pneumococcal (PCV13) 4 2 months, 4 months, 6 months, 12- ...

  15. Vaccines and animal welfare.

    PubMed

    Morton, D B

    2007-04-01

    Vaccination promotes animal welfare by protecting animal health, but it also has other welfare benefits, e.g. recent investigations have looked at the potential of vaccines in immunoneutering such as immunocastration--a humane alternative to the painful traditional methods. Similarly, vaccination can be used during disease outbreaks as a viable alternative to stamping-out, thus avoiding the welfare problems that on-farm mass slaughter can cause. Protecting animal health through vaccination leads to improved animal welfare, and maintaining good welfare ensures that animals can respond successfully to vaccination (as poor welfare can lead to immunosuppression, which can affect the response to vaccination). It is clear that vaccination has tremendous advantages for animal welfare and although the possible side effects of vaccination can have a negative effect on the welfare of some individual animals, the harm caused by these unwanted effects must be weighed against the undoubted benefits for groups of animals. PMID:17633300

  16. Clinical vaccine development

    PubMed Central

    2015-01-01

    Vaccination is regarded as one of the biggest triumphs in the history of medicine. We are living in the most successful period of vaccine development. The accumulation of multidisciplinary knowledge and the investment of massive funding have enabled the development of vaccines against many infectious diseases as well as other diseases including malignant tumors. The paradigm of clinical vaccine evaluation and licensure has also been modernized based on scientific improvements and historical experience. However, there remain a number of hurdles to overcome. Continuous efforts are focused on increasing the efficacy and reducing the risks related to vaccine use. Cutting-edge knowledge about immunology and microbiology is being rapidly translated to vaccine development. Thus, physicians and others involved in the clinical development of vaccines should have sufficient understanding of the recent developmental trends in vaccination and the diseases of interest. PMID:25648742

  17. Vaccine Reaction Images

    MedlinePlus

    ... Training Materials Q fever Info & Guidance for Clinicians Salmonella Shigella Smallpox Smallpox Basics Vaccine Basics Clinicians Vaccination ... Metals Nerve Agents Pulmonary Agents Riot Control Agents Toxic Alcohols Vesicants Chemical-Specific Fact Sheets Toxicology FAQs ...

  18. Vaccine Safety Datalink

    Cancer.gov

    The Vaccine Safety Datalink is part of the National Immunization Program within the Centers for Disease Control and Prevention and was started in recognition of gaps in the scientific knowledge of rare vaccine side effects.

  19. Role of Humoral versus Cellular Responses Induced by a Protective Dengue Vaccine Candidate

    PubMed Central

    Zellweger, Raphaël M.; Miller, Robyn; Eddy, William E.; White, Laura J.; Johnston, Robert E.; Shresta, Sujan

    2013-01-01

    With 2.5 billion people at risk, dengue is a major emerging disease threat and an escalating public health problem worldwide. Dengue virus causes disease ranging from a self-limiting febrile illness (dengue fever) to the potentially fatal dengue hemorrhagic fever/dengue shock syndrome. Severe dengue disease is associated with sub-protective levels of antibody, which exacerbate disease upon re-infection. A dengue vaccine should generate protective immunity without increasing severity of disease. To date, the determinants of vaccine-mediated protection against dengue remain unclear, and additional correlates of protection are urgently needed. Here, mice were immunized with viral replicon particles expressing the dengue envelope protein ectodomain to assess the relative contribution of humoral versus cellular immunity to protection. Vaccination with viral replicon particles provided robust protection against dengue challenge. Vaccine-induced humoral responses had the potential to either protect from or exacerbate dengue disease upon challenge, whereas cellular immune responses were beneficial. This study explores the immunological basis of protection induced by a dengue vaccine and suggests that a safe and efficient vaccine against dengue should trigger both arms of the immune system. PMID:24204271

  20. Improving Multi-Epitope Long Peptide Vaccine Potency by Using a Strategy that Enhances CD4+ T Help in BALB/c Mice

    PubMed Central

    Ghaffari-Nazari, Haniyeh; Tavakkol-Afshari, Jalil; Jaafari, Mahmoud Reza; Tahaghoghi-Hajghorbani, Sahar; Masoumi, Elham; Jalali, Seyed Amir

    2015-01-01

    Peptide-based vaccines are attractive approaches for cancer immunotherapy; but the success of these vaccines in clinical trials have been limited. Our goal is to improve immune responses and anti-tumor effects against a synthetic, multi-epitope, long peptide from rat Her2/neu (rHer2/neu) using the help of CD4+ T cells and appropriate adjuvant in a mouse tumor model. Female BALB/c mice were vaccinated with P5+435 multi-epitope long peptide that presents epitopes for cytotoxic T lymphocytes (CTL) in combination with a universal Pan DR epitope (PADRE) or CpG-oligodeoxynucleotides (CpG-ODNs) as a Toll-like receptor agonist adjuvant. The results show that vaccination with the multi-epitope long peptide in combination with the PADRE peptide and CpG-ODN induced expansion of subpopulations of CD4+ and CD8+ cells producing IFN-γ, the average tumor size in the vaccinated mice was less than that of the other groups, and tumor growth was inhibited in 40% of the mice in the vaccinated group. The mean survival time was 82.6 ± 1.25 days in mice vaccinated with P5+435 + CpG+ PADRE. Our results demonstrate that inclusion of PADRE and CpG with the peptide vaccine enhanced significant tumor specific-immune responses in vaccinated mice. PMID:26556756

  1. Improving Multi-Epitope Long Peptide Vaccine Potency by Using a Strategy that Enhances CD4+ T Help in BALB/c Mice.

    PubMed

    Ghaffari-Nazari, Haniyeh; Tavakkol-Afshari, Jalil; Jaafari, Mahmoud Reza; Tahaghoghi-Hajghorbani, Sahar; Masoumi, Elham; Jalali, Seyed Amir

    2015-01-01

    Peptide-based vaccines are attractive approaches for cancer immunotherapy; but the success of these vaccines in clinical trials have been limited. Our goal is to improve immune responses and anti-tumor effects against a synthetic, multi-epitope, long peptide from rat Her2/neu (rHer2/neu) using the help of CD4+ T cells and appropriate adjuvant in a mouse tumor model. Female BALB/c mice were vaccinated with P5+435 multi-epitope long peptide that presents epitopes for cytotoxic T lymphocytes (CTL) in combination with a universal Pan DR epitope (PADRE) or CpG-oligodeoxynucleotides (CpG-ODNs) as a Toll-like receptor agonist adjuvant. The results show that vaccination with the multi-epitope long peptide in combination with the PADRE peptide and CpG-ODN induced expansion of subpopulations of CD4+ and CD8+ cells producing IFN-γ, the average tumor size in the vaccinated mice was less than that of the other groups, and tumor growth was inhibited in 40% of the mice in the vaccinated group. The mean survival time was 82.6 ± 1.25 days in mice vaccinated with P5+435 + CpG+ PADRE. Our results demonstrate that inclusion of PADRE and CpG with the peptide vaccine enhanced significant tumor specific-immune responses in vaccinated mice. PMID:26556756

  2. Mapping the HLA ligandome landscape of acute myeloid leukemia: a targeted approach toward peptide-based immunotherapy.

    PubMed

    Berlin, C; Kowalewski, D J; Schuster, H; Mirza, N; Walz, S; Handel, M; Schmid-Horch, B; Salih, H R; Kanz, L; Rammensee, H-G; Stevanović, S; Stickel, J S

    2015-03-01

    Identification of physiologically relevant peptide vaccine targets calls for the direct analysis of the entirety of naturally presented human leukocyte antigen (HLA) ligands, termed the HLA ligandome. In this study, we implemented this direct approach using immunoprecipitation and mass spectrometry to define acute myeloid leukemia (AML)-associated peptide vaccine targets. Mapping the HLA class I ligandomes of 15 AML patients and 35 healthy controls, more than 25 000 different naturally presented HLA ligands were identified. Target prioritization based on AML exclusivity and high presentation frequency in the AML cohort identified a panel of 132 LiTAAs (ligandome-derived tumor-associated antigens), and 341 corresponding HLA ligands (LiTAPs (ligandome-derived tumor-associated peptides)) represented subset independently in >20% of AML patients. Functional characterization of LiTAPs by interferon-γ ELISPOT (Enzyme-Linked ImmunoSpot) and intracellular cytokine staining confirmed AML-specific CD8(+) T-cell recognition. Of note, our platform identified HLA ligands representing several established AML-associated antigens (e.g. NPM1, MAGED1, PRTN3, MPO, WT1), but found 80% of them to be also represented in healthy control samples. Mapping of HLA class II ligandomes provided additional CD4(+) T-cell epitopes and potentially synergistic embedded HLA ligands, allowing for complementation of a multipeptide vaccine for the immunotherapy of AML. PMID:25092142

  3. Polysaccharide-Based Vaccines

    NASA Astrophysics Data System (ADS)

    Santana, Violeta Fernández; Balbin, Yury Valdés; Calderón, Janoi Chang; Icart, Luis Peña; Verez-Bencomo, Vicente

    Capsular polysaccharides (CPS) and lipopolysaccharides from bacteria are employed for the production of vaccines against human diseases. Initial development of CPS as a vaccine was followed by the development and introduction of conjugate polysaccharide-protein vaccines. The principles leading to both developments are reviewed.

  4. Vaccines in Dermatology

    PubMed Central

    Shah, Mitali M; Shah, Aishani C; Mahajan, Rashmi S; Bilimoria, Freny E

    2015-01-01

    A vaccine is a biological preparation that improves immunity to a specific disease. More than two centuries have passed since the first successful vaccine for smallpox was developed. We’ve come a long way since. Today's vaccines are among the 21st century's most successful and cost-effective public health tools for preventing diseases. PMID:26120155

  5. A Dengue Vaccine.

    PubMed

    Durbin, Anna P

    2016-06-30

    Denvaxia is the first licensed vaccine for the prevention of dengue. It is a live vaccine developed using recombinant DNA technology. The vaccine is given as three doses over the course of a year and has the potential to prevent hundreds of thousands of hospitalizations each year. PMID:27368091

  6. Yellow Fever Vaccine

    MedlinePlus

    What is yellow fever?Yellow fever is a serious disease caused by the yellow fever virus. It is found in certain parts of Africa ... How can I prevent yellow fever?Yellow fever vaccine can prevent yellow fever. ... only at designated vaccination centers. After getting the vaccine, you ...

  7. Vaccines in dermatological diseases.

    PubMed

    Magel, G D; Mendoza, N; Digiorgio, C M; Haitz, K A; Lapolla, W J; Tyring, S K

    2011-06-01

    Vaccines have been a cornerstone in medicine and public health since their inception in the 18th century by Edward Jenner. Today, greater than 20 vaccines are used worldwide for the prevention of both viral and bacterial diseases. This article will review the vaccines used for the following dermatological diseases: smallpox, measles, mumps, rubella, chickenpox, shingles, and human papillomavirus. PMID:21566552

  8. The Use of Microwave-Assisted Solid-Phase Peptide Synthesis and Click Chemistry for the Synthesis of Vaccine Candidates Against Hookworm Infection.

    PubMed

    Fuaad, Abdullah A H Ahmad; Skwarczynski, Mariusz; Toth, Istvan

    2016-01-01

    A protein-based vaccine approach against hookworm infection has failed to deliver the expected outcome, due to a problem with an allergic response in the patient or difficulties in the proteins' production. This implication could be overcome by using a chemically synthesized peptide-based vaccine approach. This approach utilizes minimal pathogenic components that are necessary for the stimulation of the immune response without triggering adverse side effects. To boost the peptide's immunogenicity, a lipid core peptide (LCP) system can be utilized as a carrier molecule/immunostimulant. This chapter describes in detail the synthesizing of protected lipoamino acid, the self-adjuvanting moiety (LCP core), the peptide epitope, and the final vaccine candidate. The subunit peptide and the LCP core were synthesized using microwave-assisted solid-phase peptide synthesis (SPPS). Then the final hookworm vaccine construct was assembled using the copper-catalyzed azide-alkyne cycloaddition, or "click," reaction. PMID:27076158

  9. A new peptide-based urethane polymer: synthesis, biodegradation, and potential to support cell growth in vitro

    PubMed Central

    Zhang, Jian Ying; Beckman, Eric J.; Piesco, Nicholas P.; Agarwal, Sudha

    2016-01-01

    A novel non-toxic biodegradable lysine-di-isocyanate (LDI)-based urethane polymer was developed for use in tissue engineering applications. This matrix was synthesized with highly purified LDI made from the lysine diethylester. The ethyl ester of LDI was polymerized with glycerol to form a prepolymer. LDI–glycerol prepolymer when reacted with water foamed with the liberation of CO2 to provide a pliable spongy urethane polymer. The LDI–glycerol matrix degraded in aqueous solutions at 100, 37, 22, and 4°C at a rate of 27.7, 1.8, 0.8, and 0.1 mM per 10 days, respectively. Its thermal stability in water allowed its sterilization by autoclaving. The degradation of the LDI–glycerol polymer yielded lysine, ethanol, and glycerol as breakdown products. The degradation products of LDI–glycerol polymer did not significantly affect the pH of the solution. The glass transition temperature (Tg) of this polymer was found to be 103.4°C. The physical properties of the polymer network were found to be adequate to support the cell growth in vitro, as evidenced by the fact that rabbit bone marrow stromal cells (BMSC) attached to the polymer matrix and remained viable on its surface. Culture of BMSC on LDI–glycerol matrix for long durations resulted in the formation of multilayered confluent cultures, a characteristic typical of bone cells. Furthermore, cells grown on LDI–glycerol matrix did not differ phenotypically from the cells grown on the tissue culture polystyrene plates as assessed by the cell growth, and expression of mRNA for collagen type I, and transforming growth factor-β1 (TGF-β1). The observations suggest that biodegradable peptide-based urethane polymers can be synthesized which may pave their way for possible use in tissue engineering applications. PMID:10811306

  10. A Peptide-Based Positron Emission Tomography Probe for In Vivo Detection of Caspase Activity in Apoptotic Cells

    PubMed Central

    Hight, Matthew R.; Cheung, Yiu-Yin; Nickels, Michael L.; Dawson, Eric S.; Zhao, Ping; Saleh, Samir; Buck, Jason R.; Tang, Dewei; Washington, M. Kay; Coffey, Robert J.; Manning, H. Charles

    2014-01-01

    Purpose Apoptosis, or programmed cell death, can be leveraged as a surrogate measure of response to therapeutic interventions in medicine. Cysteine aspartic acid-specific proteases, or caspases, are essential determinants of apoptosis signaling cascades and represent promising targets for molecular imaging. Here, we report development and in vivo validation of [18F]4-fluorobenzylcarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone ([18F]FB-VAD-FMK), a novel peptide-based molecular probe suitable for quantification of caspase activity in vivo using positron emission tomography (PET). Experimental Design Supported by molecular modeling studies and subsequent in vitro assays suggesting probe feasibility the labeled pan-caspase inhibitory peptide, [18F]FB-VAD-FMK, was produced in high radiochemical yield and purity using a simple two-step, radiofluorination. The biodistribution of [18F]FB-VAD-FMK in normal tissue and its efficacy to predict response to molecularly targeted therapy in tumors was evaluated using microPET imaging of mouse models of human colorectal cancer (CRC). Results Accumulation of [18F]FB-VAD-FMK was found to agree with elevated caspase-3 activity in response to Aurora B kinase inhibition as well as a multi-drug regimen that combined an inhibitor of mutant BRAF and a dual PI3K/mTOR inhibitor in V600EBRAF colon cancer. In the latter setting, [18F]FB-VAD-FMK PET was also elevated in the tumors of cohorts that exhibited reduction in size. Conclusions These studies illuminate [18F]FB-VAD-FMK as a promising PET imaging probe to detect apoptosis in tumors and as a novel, potentially translatable biomarker for predicting response to personalized medicine. PMID:24573549

  11. Importance of vaccination habit and vaccine choice on influenza vaccination among healthy working adults.

    PubMed

    Lin, Chyongchiou J; Nowalk, Mary Patricia; Toback, Seth L; Rousculp, Matthew D; Raymund, Mahlon; Ambrose, Christopher S; Zimmerman, Richard K

    2010-11-10

    This randomized cluster trial was designed to improve workplace influenza vaccination rates using enhanced advertising, choice of vaccine type (intranasal or injectable) and an incentive. Workers aged 18-49 years were surveyed immediately following vaccination to determine factors associated with vaccination behavior and choice. The questionnaire assessed attitudes, beliefs and social support for influenza vaccine, demographics, and historical, current, and intentional vaccination behavior. Of the 2389 vaccinees, 83.3% received injectable vaccine and 16.7% received intranasal vaccine. Factors associated with previous influenza vaccination were older age, female sex, higher education and greater support for injectable vaccine (all P<.02). Current influenza vaccination with intranasal vaccine vs. injectable vaccine was associated with higher education, the study interventions, greater support for the intranasal vaccine and nasal sprays, less support of injectable vaccine, more negative attitudes about influenza vaccine, and a greater likelihood of reporting that the individual would not have been vaccinated had only injectable vaccine been offered (all P<.01). Intentional vaccine choice was most highly associated with previous vaccination behavior (P<.001). A key to long term improvements in workplace vaccination is to encourage first time influenza vaccination through interventions that include incentives, publicity and vaccine choice. PMID:20638452

  12. C-Peptide-Based Index Is More Related to Incident Type 2 Diabetes in Non-Diabetic Subjects than Insulin-Based Index

    PubMed Central

    Kang, Sung Ju; Lee, Min Kyung; Park, Se Eun; Rhee, Eun Jung; Park, Cheol-Young; Oh, Ki-Won; Park, Sung-Woo

    2016-01-01

    Background Diabetes can be efficiently prevented by life style modification and medical therapy. So, identification for high risk subjects for incident type 2 diabetes is important. The aim of this study is to identify the best β-cell function index to identify high risk subjects in non-diabetic Koreans. Methods This is a retrospective longitudinal study. Total 140 non-diabetic subjects who underwent standard 2-hour 75 g oral glucose tolerance test from January 2007 to February 2007 at Kangbuk Samsung Hospital and followed up for more than 1 year were analyzed (mean follow-up, 54.9±16.4 months). The subjects were consist of subjects with normal glucose tolerance (n=44) and subjects with prediabetes (n=97) who were 20 years of age or older. Samples for insulin and C-peptide levels were obtained at 0 and 30 minutes at baseline. Results Thirty subjects out of 140 subjects (21.4%) developed type 2 diabetes. When insulin-based index and C-peptide-based index are compared between progressor and non-progressor to diabetes, all C-peptide-based indices were statistically different between two groups, but only insulinogenic index and disposition index among insulin-based index were statistically different. C-peptide-based index had higher value of area under receiver operating characteristic curve (AROC) value than that of insulin-based index. "C-peptidogenic" index had highest AROC value among indices (AROC, 0.850; 95% confidence interval, 0.761 to 0.915). C-peptidogenic index had significantly higher AROC than insulinogenic index (0.850 vs. 0.731 respectively; P=0.014). Conclusion C-peptide-based index was more closely related to incident type 2 diabetes in non-diabetic subjects than insulin-based index. PMID:27349701

  13. Immunogenicity and Safety of Influenza Vaccination in Systemic Lupus Erythematosus Patients Compared with Healthy Controls: A Meta-Analysis

    PubMed Central

    Liao, Zhengfa; Tang, Hao; Xu, Xiaojia; Liang, Yaping; Xiong, Yongzhen; Ni, Jindong

    2016-01-01

    Objective To assess the immunogenicity and safety of influenza vaccine in patients with systemic lupus erythematosus (SLE). Methods Relevant articles were retrieved from electronic databases. Seroprotection rate, seroconversion rate and factors that increase antibody geometric mean titer (GMT) were used as indices to measure the immunogenicity. The safety of vaccine was assessed through monitoring adverse events, which included side effects and SLE exacerbations. We performed a meta-analysis of influenza vaccine seroprotection, seroconversion and adverse effects. SLE exacerbation after vaccination was comprehensively described. We used the Committee for Proprietary Medicinal Products (CPMP) guidelines to determine whether influenza can induce adequate immunogenicity in patients with SLE. Results Eighteen studies with 1966 subjects met the inclusion criteria. At least 565 of the subjects were patients with low-to-moderate SLE Disease Activity Index (SLEDAI) score or stable SLE disease. Compared with the general population, seroprotection rate in SLE patients was significantly decreased in patients with H1N1 [odds ratio (OR) = 0.36, 95% confidence interval (CI): 0.27–0.50] and H3N2 vaccination (OR = 0.48, 95% CI: 0.24–0.93), but not influenza B vaccination (OR = 0.55, 95% CI: 0.24–1.25). Seroconversion rate also significantly decreased in patients with H1N1 (OR = 0.39, 95% CI: 0.27–0.57) and influenza B (OR = 0.47, 95% CI: 0.29–0.76) vaccination, but not H3N2 vaccination (OR = 0.62, 95% CI: 0.21–1.79). However, the immunogenicity of influenza vaccine in SLE patients almost reached that of the CPMP guidelines. The OR for side effects (patients versus healthy controls) was 3.24 (95% CI: 0.62–16.76). Among 1966 patients with SLE, 32 experienced mild exacerbation of SLE and five had serious side effects for other reasons. Conclusion Influenza vaccine has moderate effect on protecting patients with SLE. The side effects of influenza vaccine are not serious

  14. Suspected acute exacerbation of idiopathic pulmonary fibrosis as an outcome measure in clinical trials

    PubMed Central

    2013-01-01

    Background Acute exacerbation of idiopathic pulmonary fibrosis has become an important outcome measure in clinical trials. This study aimed to explore the concept of suspected acute exacerbation as an outcome measure. Methods Three investigators retrospectively reviewed subjects enrolled in the Sildenafil Trial of Exercise Performance in IPF who experienced a respiratory serious adverse event during the course of the study. Events were classified as definite acute exacerbation, suspected acute exacerbation, or other, according to established criteria. Results Thirty-five events were identified. Four were classified as definite acute exacerbation, fourteen as suspected acute exacerbation, and seventeen as other. Definite and suspected acute exacerbations were clinically indistinguishable. Both were most common in the winter and spring months and were associated with a high risk of disease progression and short-term mortality. Conclusions In this study one half of respiratory serious adverse events were attributed to definite or suspected acute exacerbations. Suspected acute exacerbations are clinically indistinguishable from definite acute exacerbations and represent clinically meaningful events. Clinical trialists should consider capturing both definite and suspected acute exacerbations as outcome measures. PMID:23848435

  15. Human immunodeficiency virus vaccines.

    PubMed

    Goepfert, Paul; Bansal, Anju

    2014-12-01

    Although some success was achieved in recent years in HIV prevention, an effective vaccine remains the means with the most potential of curtailing HIV-1 infections worldwide. Despite multiple failed attempts, a recent HIV vaccine regimen demonstrated modest protection from infection. Although the protective efficacy in this trial was not sufficient to warrant licensure, it spurred renewed optimism in the field and has provided valuable insights for improving future vaccine designs. This review summarizes the pertinent details of vaccine development and discusses ways the field is moving forward to develop a vaccine to prevent HIV infection and disease progression. PMID:25287587

  16. Vaccination for Disease

    NASA Astrophysics Data System (ADS)

    Oehen, Stephan; Hengartner, Hans; Zinkernagel, Rolf M.

    1991-01-01

    Recombinant virus vaccines that express a limited number of epitopes are currently being developed to prevent disease by changing the relative balance between viral spread and the immune response. Some circumstances, however, were found in infections with a noncytopathic virus in which vaccination caused disease; sensitive parameters included the genetic background of the host, the time or dose of infection, and the constituents of the vaccine. Thus, immunopathologic damage by T cells may be an unwanted consequence of vaccination with the new types of peptide or recombinant vaccines that are being investigated for the human immunodeficiency viruses and other pathogens.

  17. Vaccine-Associated Uveitis.

    PubMed

    Benage, Matthew; Fraunfelder, Frederick W

    2016-01-01

    All of the widely administered vaccines have been reported to cause uveitis. The ocular inflammation is usually temporary and resolves with topical ocular steroids. During a 26-year period, a total of 289 cases of vaccine-associated uveitis were reported to three adverse reaction reporting databases. Hepatitis B vaccine, either alone or administered with other vaccines, appears to be the leading offender. Clinicians are encouraged to report cases of vaccine- or drug-associated ocular adverse reactions to www.eyedrugregistry.com. PMID:27039491

  18. Daily activity during stability and exacerbation of chronic obstructive pulmonary disease

    PubMed Central

    2014-01-01

    Background During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data. Methods Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer. Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators. Results The 73 COPD patients (88% male) had a mean (±SD) age 71(±8) years and FEV1 53(±16)% predicted. They recorded pedometer data on a median 198 days (IQR 134–353). At exacerbation onset, symptom count rose by 1.9(±1.3) and PEF fell by 7(±13) l/min. Mean daily step count fell from 4154(±2586) steps/day during a preceding baseline week to 3673(±2258) step/day during the initial 7 days of exacerbation (p = 0.045). Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = −0.56; p < 0.001). Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001). Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030). Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002). Conclusions COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time. PMID:24885188

  19. Predictors of Hospitalized Exacerbations and Mortality in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Santibáñez, Miguel; Garrastazu, Roberto; Ruiz-Nuñez, Mario; Helguera, Jose Manuel; Arenal, Sandra; Bonnardeux, Cristina; León, Carlos; García-Rivero, Juan Luis

    2016-01-01

    Background and Aim Exacerbations of chronic obstructive pulmonary disease (COPD) carry significant consequences for patients and are responsible for considerable health-care costs—particularly if hospitalization is required. Despite the importance of hospitalized exacerbations, relatively little is known about their determinants. This study aimed to analyze predictors of hospitalized exacerbations and mortality in COPD patients. Methods This was a retrospective population-based cohort study. We selected 900 patients with confirmed COPD aged ≥35 years by simple random sampling among all COPD patients in Cantabria (northern Spain) on December 31, 2011. We defined moderate exacerbations as events that led a care provider to prescribe antibiotics or corticosteroids and severe exacerbations as exacerbations requiring hospital admission. We observed exacerbation frequency over the previous year (2011) and following year (2012). We categorized patients according to COPD severity based on forced expiratory volume in 1 second (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 1–4). We estimated the odds ratios (ORs) by logistic regression, adjusting for age, sex, smoking status, COPD severity, and frequent exacerbator phenotype the previous year. Results Of the patients, 16.4% had ≥1 severe exacerbations, varying from 9.3% in mild GOLD grade 1 to 44% in very severe COPD patients. A history of at least two prior severe exacerbations was positively associated with new severe exacerbations (adjusted OR, 6.73; 95% confidence interval [CI], 3.53–12.83) and mortality (adjusted OR, 7.63; 95%CI, 3.41–17.05). Older age and several comorbidities, such as heart failure and diabetes, were similarly associated. Conclusions Hospitalized exacerbations occurred with all grades of airflow limitation. A history of severe exacerbations was associated with new hospitalized exacerbations and mortality. PMID:27362765

  20. Vaccinations for Pregnant Women

    PubMed Central

    Swamy, Geeta K.; Heine, R. Phillips

    2014-01-01

    In the United States, eradication and reduction of vaccine-preventable diseases through immunization has directly increased life expectancy by reducing mortality. Although immunization is a public priority, vaccine coverage among adult Americans is inadequate. The Institute of Medicine, the Community Preventive Services Task Force, and other public health entities have called for the development of innovative programs to incorporate adult vaccination into routine clinical practice. Obstetrician–gynecologists are well-suited to serve as vaccinators of women in general and more specifically pregnant women. Pregnant women are at risk for vaccine-preventable disease–related morbidity and mortality and adverse pregnancy outcomes, including congenital anomalies, spontaneous abortion, preterm birth, and low birth weight. In addition to providing direct maternal benefit, vaccination during pregnancy likely provides direct fetal and infant benefit through passive immunity (transplacental transfer of maternal vaccine-induced antibodies). This article reviews: 1) types of vaccines; 2) vaccines specifically recommended during pregnancy and postpartum; 3) vaccines recommended during pregnancy and postpartum based on risk factors and special circumstances; 4) vaccines currently under research and development for licensure for maternal-fetal immunization; and 5) barriers to maternal immunization and available patient and provider resources. PMID:25560127

  1. Emerging Vaccine Informatics

    PubMed Central

    He, Yongqun; Rappuoli, Rino; De Groot, Anne S.; Chen, Robert T.

    2010-01-01

    Vaccine informatics is an emerging research area that focuses on development and applications of bioinformatics methods that can be used to facilitate every aspect of the preclinical, clinical, and postlicensure vaccine enterprises. Many immunoinformatics algorithms and resources have been developed to predict T- and B-cell immune epitopes for epitope vaccine development and protective immunity analysis. Vaccine protein candidates are predictable in silico from genome sequences using reverse vaccinology. Systematic transcriptomics and proteomics gene expression analyses facilitate rational vaccine design and identification of gene responses that are correlates of protection in vivo. Mathematical simulations have been used to model host-pathogen interactions and improve vaccine production and vaccination protocols. Computational methods have also been used for development of immunization registries or immunization information systems, assessment of vaccine safety and efficacy, and immunization modeling. Computational literature mining and databases effectively process, mine, and store large amounts of vaccine literature and data. Vaccine Ontology (VO) has been initiated to integrate various vaccine data and support automated reasoning. PMID:21772787

  2. Vaccinations for pregnant women.

    PubMed

    Swamy, Geeta K; Heine, R Phillips

    2015-01-01

    In the United States, eradication and reduction of vaccine-preventable diseases through immunization has directly increased life expectancy by reducing mortality. Although immunization is a public priority, vaccine coverage among adult Americans is inadequate. The Institute of Medicine, the Community Preventive Services Task Force, and other public health entities have called for the development of innovative programs to incorporate adult vaccination into routine clinical practice. Obstetrician-gynecologists are well suited to serve as vaccinators of women in general and more specifically pregnant women. Pregnant women are at risk for vaccine-preventable disease-related morbidity and mortality and adverse pregnancy outcomes, including congenital anomalies, spontaneous abortion, preterm birth, and low birth weight. In addition to providing direct maternal benefit, vaccination during pregnancy likely provides direct fetal and neonatal benefit through passive immunity (transplacental transfer of maternal vaccine-induced antibodies). This article reviews: 1) types of vaccines; 2) vaccines specifically recommended during pregnancy and postpartum; 3) vaccines recommended during pregnancy and postpartum based on risk factors and special circumstances; 4) vaccines currently under research and development for licensure for maternal-fetal immunization; and 5) barriers to maternal immunization and available patient and health care provider resources. PMID:25560127

  3. Cervical spinal cord injury exacerbates ventilator-induced diaphragm dysfunction.

    PubMed

    Smuder, Ashley J; Gonzalez-Rothi, Elisa J; Kwon, Oh Sung; Morton, Aaron B; Sollanek, Kurt J; Powers, Scott K; Fuller, David D

    2016-01-15

    Cervical spinal cord injury (SCI) can dramatically impair diaphragm muscle function and often necessitates mechanical ventilation (MV) to maintain adequate pulmonary gas exchange. MV is a life-saving intervention. However, prolonged MV results in atrophy and impaired function of the diaphragm. Since cervical SCI can also trigger diaphragm atrophy, it may create preconditions that exacerbate ventilator-induced diaphragm dysfunction (VIDD). Currently, no drug therapy or clinical standard of care exists to prevent or minimize diaphragm dysfunction following SCI. Therefore, we first tested the hypothesis that initiating MV acutely after cervical SCI will exacerbate VIDD and enhance proteolytic activation in the diaphragm to a greater extent than either condition alone. Rats underwent controlled MV for 12 h following acute (∼24 h) cervical spinal hemisection injury at C2 (SCI). Diaphragm tissue was then harvested for comprehensive functional and molecular analyses. Second, we determined if antioxidant therapy could mitigate MV-induced diaphragm dysfunction after cervical SCI. In these experiments, SCI rats received antioxidant (Trolox, a vitamin E analog) or saline treatment prior to initiating MV. Our results demonstrate that compared with either condition alone, the combination of SCI and MV resulted in increased diaphragm atrophy, contractile dysfunction, and expression of atrophy-related genes, including MuRF1. Importantly, administration of the antioxidant Trolox attenuated proteolytic activation, fiber atrophy, and contractile dysfunction in the diaphragms of SCI + MV animals. These findings provide evidence that cervical SCI greatly exacerbates VIDD, but antioxidant therapy with Trolox can preserve diaphragm contractile function following acute SCI. PMID:26472866

  4. Vaccines for allergy

    PubMed Central

    Linhart, Birgit; Valenta, Rudolf

    2012-01-01

    Vaccines aim to establish or strengthen immune responses but are also effective for the treatment of allergy. The latter is surprising because allergy represents a hyper-immune response based on immunoglobulin E production against harmless environmental antigens, i.e., allergens. Nevertheless, vaccination with allergens, termed allergen-specific immunotherapy is the only disease-modifying therapy of allergy with long-lasting effects. New forms of allergy diagnosis and allergy vaccines based on recombinant allergen-derivatives, peptides and allergen genes have emerged through molecular allergen characterization. The molecular allergy vaccines allow sophisticated targeting of the immune system and may eliminate side effects which so far have limited the use of traditional allergen extract-based vaccines. Successful clinical trials performed with the new vaccines indicate that broad allergy vaccination is on the horizon and may help to control the allergy pandemic. PMID:22521141

  5. Vaccines for allergy.

    PubMed

    Linhart, Birgit; Valenta, Rudolf

    2012-06-01

    Vaccines aim to establish or strengthen immune responses but are also effective for the treatment of allergy. The latter is surprising because allergy represents a hyper-immune response based on immunoglobulin E production against harmless environmental antigens, i.e., allergens. Nevertheless, vaccination with allergens, termed allergen-specific immunotherapy is the only disease-modifying therapy of allergy with long-lasting effects. New forms of allergy diagnosis and allergy vaccines based on recombinant allergen-derivatives, peptides and allergen genes have emerged through molecular allergen characterization. The molecular allergy vaccines allow sophisticated targeting of the immune system and may eliminate side effects which so far have limited the use of traditional allergen extract-based vaccines. Successful clinical trials performed with the new vaccines indicate that broad allergy vaccination is on the horizon and may help to control the allergy pandemic. PMID:22521141

  6. Immunology of vaccination.

    PubMed

    Beverley, P C L

    2002-01-01

    An ideal vaccine is relatively easy to define, but few real vaccines approach the ideal and no vaccines exist for many organisms, for which a vaccine is the only realistic protective strategy in the foreseeable future. Many difficulties account for the failure to produce these vaccines. All micro-organisms deploy evasion mechanisms that interfere with effective immune responses and, for many organisms, it is not clear which immune responses provide effective protection. However, recent advances in methods for studying immune response to pathogens have provided a better understanding of immune mechanisms, including immunological memory, and led to the realisation that the initiation of immune responses is a key event requiring triggering through 'danger' signals. Based on these findings, the development of novel adjuvants, vectors and vaccine formulations allowing stimulation of optimal and prolonged protective immunity should lead to the introduction of vaccines for previously resistant organisms. PMID:12176847

  7. Vaccine epidemiology: A review

    PubMed Central

    Lahariya, Chandrakant

    2016-01-01

    This review article outlines the key concepts in vaccine epidemiology, such as basic reproductive numbers, force of infection, vaccine efficacy and effectiveness, vaccine failure, herd immunity, herd effect, epidemiological shift, disease modeling, and describes the application of this knowledge both at program levels and in the practice by family physicians, epidemiologists, and pediatricians. A case has been made for increased knowledge and understanding of vaccine epidemiology among key stakeholders including policy makers, immunization program managers, public health experts, pediatricians, family physicians, and other experts/individuals involved in immunization service delivery. It has been argued that knowledge of vaccine epidemiology which is likely to benefit the society through contributions to the informed decision-making and improving vaccination coverage in the low and middle income countries (LMICs). The article ends with suggestions for the provision of systematic training and learning platforms in vaccine epidemiology to save millions of preventable deaths and improve health outcomes through life-course. PMID:27453836

  8. [Vaccinations for the travellers].

    PubMed

    Gendrel, Dominique

    2004-03-15

    Immunisations for the traveller include, before specific vaccine, a correct immunisation schedule according to national recommendations with appropriate boosters and hepatitis B immunisation. The yellow fever vaccine is required to entry in countries of endemic area and quadrivalent ACYW135 meningococcal vaccine for entry in Saudi Arabia. Hepatitis A immunisation could be performed at 1 year of age and is recommended for travellers in tropical areas and children vaccination control the disease both in the patient and in the contacts. Meningococcal A+C vaccines are required for travellers in meningitis-prone areas of tropical Africa during the dry season (December to June), and quadrivalent ACYW135 is useful only in Burkina-Faso and Niger. Typhoid and rabies vaccines are required for ambulatory travellers in endemic areas, as Japanese encephalitis in south-west Asia. In central Europe, tick-borne encephalitis vaccination is recommended for patients travelling in forest areas during spring and summer. PMID:15176511

  9. Update on the Management of Aspirin-Exacerbated Respiratory Disease.

    PubMed

    Buchheit, Kathleen M; Laidlaw, Tanya M

    2016-07-01

    Aspirin-exacerbated respiratory disease (AERD) is an adult-onset upper and lower airway disease consisting of eosinophilic nasal polyps, asthma, and respiratory reactions to cyclooxygenase 1 (COX-1) inhibitors. Management includes guideline-based treatment of asthma and sinus disease, avoidance of COX-1 inhibitors, and for some patients aspirin desensitization followed by high-dose aspirin therapy. Despite this, many patients have inadequately controlled symptoms and require multiple sinus surgeries. In this review, we discuss the current standard approaches to the management of AERD, and we introduce several therapeutics under development that may hold promise for the treatment of AERD. PMID:27126722

  10. [How I prevent...exacerbation of atopic dermatitis].

    PubMed

    Xhauflaire-Uhoda, E; Piérard-Franchimont, C; Nikkels, A F; Piérard, G E

    2006-01-01

    Atopic dermatitis is under the influence of series of environmental factors. The contact with unsuited cleaning agents and rough textiles can exacerbate pruritus and inflammation. Preventive and adjuvant measures can thus help the care procedures of the disease. Appropriate hygiene measures and the use of emollients are particularly helpful. Clothing measures are also in place. Undergarments and pyjamas made of knitted natural silk are available. Other measures, sometimes corresponding to anecdotal claims--antihistamines, thermal cures, unconventional medicine, probiotics, chinese herbals, essential fatty acids--have not proven their preventive efficacy in atopic dermatitis. PMID:17020235

  11. Cold Storage Exacerbates Renal and Mitochondrial Dysfunction Following Transplantation

    PubMed Central

    Shrum, S; MacMillan-Crow, LA; Parajuli, N

    2016-01-01

    Long-term renal function is compromised in patients receiving deceased donor kidneys which require cold storage exposure prior to transplantation. It is well established that extended cold storage induces renal damage and several labs, including our own, have demonstrated renal mitochondrial damage after cold storage alone. However, to our knowledge, few studies have assessed renal and mitochondrial function after transplantation of rat kidneys exposed to short-term (4 hr) cold storage compared to transplant without cold storage (autotransplantation). Our data reveal that cold storage plus transplantation exacerbated renal and mitochondrial dysfunction when compared to autotransplantation alone. PMID:27066594

  12. Mould counts and exacerbations of allergic bronchopulmonary aspergillosis.

    PubMed

    Radin, R C; Greenberger, P A; Patterson, R; Ghory, A

    1983-05-01

    The purpose of this study was to determine whether exacerbations of allergic bronchopulmonary aspergillosis (ABPA) were associated with the total outdoor mould counts in the Chicago area. From 1976-1980, forty-nine flares of ABPA (new pulmonary infiltrate with elevation in total serum IgE) occurred in nineteen patients. Thirty-eight (77.5%) of flares occurred during months June through November in association with increased outdoor mould counts in Chicago. This association confirms earlier observations from the U.K. where during the peak mould season which occurs in winter months, there was an increased number of pulmonary infiltrates and average prednisone doses required in ABPA. PMID:6342846

  13. Update on the Management of Aspirin-Exacerbated Respiratory Disease

    PubMed Central

    Laidlaw, Tanya M.

    2016-01-01

    Aspirin-exacerbated respiratory disease (AERD) is an adult-onset upper and lower airway disease consisting of eosinophilic nasal polyps, asthma, and respiratory reactions to cyclooxygenase 1 (COX-1) inhibitors. Management includes guideline-based treatment of asthma and sinus disease, avoidance of COX-1 inhibitors, and for some patients aspirin desensitization followed by high-dose aspirin therapy. Despite this, many patients have inadequately controlled symptoms and require multiple sinus surgeries. In this review, we discuss the current standard approaches to the management of AERD, and we introduce several therapeutics under development that may hold promise for the treatment of AERD. PMID:27126722

  14. Aspirin-exacerbated respiratory disease: pathophysiological insights and clinical advances

    PubMed Central

    Steinke, John W; Wilson, Jeff M

    2016-01-01

    Asthma and chronic rhinosinusitis are heterogeneous airway diseases of the lower and upper airways, respectively. Molecular and cellular studies indicate that these diseases can be categorized into unique endotypes, which have therapeutic implications. One such endotype is aspirin-exacerbated respiratory disease (AERD), which encompasses the triad of asthma, aspirin (or nonsteroidal anti-inflammatory drug) hypersensitivity, and nasal polyposis. AERD has unique pathophysiological features that distinguish it from aspirin-tolerant asthma and other forms of chronic rhinosinusitis. This review details molecular and cellular features of AERD and highlights current and future therapies that are based on these insights. PMID:27022293

  15. Aspirin-exacerbated respiratory disease: pathophysiological insights and clinical advances.

    PubMed

    Steinke, John W; Wilson, Jeff M

    2016-01-01

    Asthma and chronic rhinosinusitis are heterogeneous airway diseases of the lower and upper airways, respectively. Molecular and cellular studies indicate that these diseases can be categorized into unique endotypes, which have therapeutic implications. One such endotype is aspirin-exacerbated respiratory disease (AERD), which encompasses the triad of asthma, aspirin (or nonsteroidal anti-inflammatory drug) hypersensitivity, and nasal polyposis. AERD has unique pathophysiological features that distinguish it from aspirin-tolerant asthma and other forms of chronic rhinosinusitis. This review details molecular and cellular features of AERD and highlights current and future therapies that are based on these insights. PMID:27022293

  16. New tuberculosis vaccines.

    PubMed

    Martín Montañés, Carlos; Gicquel, Brigitte

    2011-03-01

    The current tuberculosis (TB) vaccine, bacille Calmette-Guerin (BCG), is a live vaccine used worldwide, as it protects against severe forms of the disease, saving thousands of lives every year, but its efficacy against pulmonary forms of TB, responsible for transmission of the diseases, is variable. For more than 80 years now no new TB vaccines have been successfully developed. Over the last decade the effort of the scientific community has resulted in the design and construction of promising vaccine candidates. The goal is to develop a new generation of vaccines effective against respiratory forms of the disease. We will focus this review on new prophylactic vaccine candidates that aim to prevent TB diseases. Two are the main strategies used to improve the immunity conferred by the current BCG vaccine, by boosting it with new subunit vaccines, and a second strategy is focused on the construction of new more effective live vaccines, capable to replace the current BCG and to be used as prime vaccines. After rigorous preclinical studies in different animal models new TB vaccine candidates enter in clinical trials in humans. First, a small Phase I for safety followed by immunological evaluation in Phase II trials and finally evaluated in large population Phase III efficacy trials in endemic countries. At present BCG prime and boost with different subunit vaccine candidates are the more advanced assessed in Phase II. Two prime vaccines (based on recombinant BCG) have been successfully evaluated for safety in Phase I trials. A short number of live attenuated vaccines are in advance preclinical studies and the candidates ready to enter Phase I safety trials are produced under current good manufacturing practices. PMID:21420568

  17. Recommended routine vaccinations for older adults.

    PubMed

    Planton, Jonathan; Meyer, Jennifer O; Edlund, Barbara J

    2012-07-01

    A goal of primary prevention is to avoid the development of disease. Immunizations are one of several strategies used by clinicians in primary prevention. Influenza and pneumococcal disease--both preventable--cause significant morbidity and mortality in older adults who have an altered immune system, often have several chronic health problems, and are at higher risk for complications. Tetanus, while not as common in older adults, carries a high mortality rate in those 65 and older. These infections are associated with significant disability that results from hospitalizations for congestive heart failure, hip fracture, stroke, and pneumonia. The goal of immunizing older adults is to decrease functional decline and disability, as well as potential hospital admissions linked to these preventable diseases, which often exacerbate underlying health problems. Age-defined recommendations are available to guide clinicians on the appropriate vaccinations and schedules for administration to older adults. PMID:22715960

  18. Current progress in the development of therapeutic vaccines for chronic hepatitis B virus infection

    PubMed Central

    Ghasemi, Faezeh; Rostami, Sina; Ghayour-Mobarhan, Majid; Meshkat, Zahra

    2016-01-01

    Chronic hepatitis B is still a major public health issue despite the successful prophylactic vaccination attempts. Chronicity of hepatitis B virus (HBV) is mainly due to its ability to debilitate host’s immune system. Therefore, major measures have been taken to stop this process and help patients with chronic hepatitis B infection recover from their illness. While satisfactory results have been achieved using preventive HBV vaccines, a reliable and effective therapeutic treatment is still in need of extensive studies. Current treatments for chronic hepatitis B include direct antiviral agents and nucleoside/nucleotide analogs, which are not always effective and are also costly. In addition, due to the fact that chronic HBV is responsible for debilitation of the immune system, studies have focused on developing therapeutic vaccines to help host’s immune system recover and limit the infection. Several approaches including but not restricted to recombinant peptide-based, DNA-based, viral vector-based, and cell-based approaches are currently in use to develop therapeutic vaccines against the chronic form of HBV infection. In the current review, the authors will first discuss the role of the immune system in chronic hepatitis B infection and will then focus on latest advancements in therapeutic vaccination of HBV especially the clinical trials that have been carried out so far.

  19. Efficacy of combined vaccination against Mycoplasma hyopneumoniae and porcine reproductive and respiratory syndrome virus in dually infected pigs.

    PubMed

    Bourry, Olivier; Fablet, Christelle; Simon, Gaëlle; Marois-Créhan, Corinne

    2015-11-18

    Porcine respiratory disease complex (PRDC) is one of the main causes of economic losses for swine producers. This complex is due to a combination of different pathogens and their interactions. Two major pathogens involved in PRDC are Mycoplasma hyopneumoniae (Mhp) and porcine reproductive and respiratory syndrome virus (PRRSV). The objectives of this study were (i) to develop an experimental model of dual Mhp/PRRSV infection in SPF pigs with European strains of Mhp and PRRSV and (ii) to assess and compare the effects of single Mhp, single PRRSV or combined Mhp/PRRSV vaccination against this dual infection. Pigs dually infected with Mhp and PRRSV showed a combination of symptoms characteristic of each pathogen but no significant exacerbation of pathogenicity. Thus, the co-infected pigs displayed coughing and pneumonia typical of Mhp infection in addition to PRRSV-related hyperthermia and decrease in average daily gain (ADG). Hyperthermia was reduced in PRRSV vaccinated animals (single or combined vaccination), whereas ADG was restored in Mhp/PRRSV vaccinated pigs only. Regarding respiratory symptoms and lung lesions, no vaccine decreased coughing. However, all vaccines reduced the pneumonia score but more so in animals receiving the Mhp vaccine, whether single or combined. This vaccine also decreased the Mhp load in the respiratory tract. In conclusion, combined vaccination against both Mhp and PRRSV efficiently pooled the efficacy of each single PRRSV and Mhp vaccination and could be an interesting tool to control PRDC in European swine production. PMID:26422712

  20. Incidence and outcomes of patients hospitalized with COPD exacerbation with and without pneumonia

    PubMed Central

    Søgaard, Mette; Madsen, Morten; Løkke, Anders; Hilberg, Ole; Sørensen, Henrik Toft; Thomsen, Reimar W

    2016-01-01

    Background Pneumonia may be a major contributor to hospitalizations for chronic obstructive pulmonary disease (COPD) exacerbation and influence their outcomes. Methods We examined hospitalization rates, health resource utilization, 30-day mortality, and risk of subsequent hospitalizations for COPD exacerbations with and without pneumonia in Denmark during 2006–2012. Results We identified 179,759 hospitalizations for COPD exacerbations, including 52,520 first-time hospitalizations (29.2%). Pneumonia was frequent in first-time exacerbations (36.1%), but declined in successive exacerbations to 25.6% by the seventh or greater exacerbation. Pneumonic COPD exacerbations increased 20% from 0.92 per 1,000 population in 2006 to 1.10 per 1,000 population in 2012. Nonpneumonic exacerbations decreased by 6% from 1.74 per 1,000 population to 1.63 per 1,000 population during the same period. A number of markers of health resource utilization were more prevalent in pneumonic exacerbations than in nonpneumonic exacerbations: length of stay (median 7 vs 4 days), intensive care unit admission (7.7% vs 12.5%), and several acute procedures. Thirty-day mortality was 12.1% in first-time pneumonic COPD exacerbations versus 8.3% in first-time nonpneumonic cases (adjusted HR [aHR] 1.20, 95% confidence interval [CI] 1.17–1.24). Pneumonia also predicted increased mortality associated with a second exacerbation (aHR 1.14, 95% CI 1.11–1.18), and up to a seventh or greater exacerbation (aHR 1.10, 95% CI 1.07–1.13). In contrast, the aHR of a subsequent exacerbation was 8%–13% lower for patients with pneumonic exacerbations. Conclusions Pneumonia is frequent among patients hospitalized for COPD exacerbations and is associated with increased health care utilization and higher mortality. Nonpneumonic COPD exacerbations predict increased risk of subsequent exacerbations. PMID:27042038

  1. Influenza Vaccines: Challenges and Solutions

    PubMed Central

    Houser, Katherine; Subbarao, Kanta

    2015-01-01

    Vaccination is the best method for the prevention and control of influenza. Vaccination can reduce illness and lessen severity of infection. This review focuses on how currently licensed influenza vaccines are generated in the U.S., why the biology of influenza poses vaccine challenges, and vaccine approaches on the horizon that address these challenges. PMID:25766291

  2. Pharmacological strategies to reduce exacerbation risk in COPD: a narrative review.

    PubMed

    Miravitlles, Marc; D'Urzo, Anthony; Singh, Dave; Koblizek, Vladimir

    2016-01-01

    Identifying patients at risk of exacerbations and managing them appropriately to reduce this risk represents an important clinical challenge. Numerous treatments have been assessed for the prevention of exacerbations and their efficacy may differ by patient phenotype. Given their centrality in the treatment of COPD, there is strong rationale for maximizing bronchodilation as an initial strategy to reduce exacerbation risk irrespective of patient phenotype. Therefore, in patients assessed as frequent exacerbators (>1 exacerbation/year) we propose initial bronchodilator treatment with a long-acting muscarinic antagonist (LAMA)/ long-acting β2-agonist (LABA). For those patients who continue to experience >1 exacerbation/year despite maximal bronchodilation, we advocate treating according to patient phenotype. Based on currently available data on adding inhaled corticosteroids (ICS) to a LABA, ICS might be added to a LABA/LAMA combination in exacerbating patients who have an asthma-COPD overlap syndrome or high blood eosinophil counts, while in exacerbators with chronic bronchitis, consideration should be given to treating with a phosphodiesterase (PDE)-4 inhibitor (roflumilast) or high-dose mucolytic agents. For those patients who experience frequent bacterial exacerbations and/or bronchiectasis, addition of mucolytic agents or a macrolide antibiotic (e.g. azithromycin) should be considered. In all patients at risk of exacerbations, pulmonary rehabilitation should be included as part of a comprehensive management plan. PMID:27613392

  3. [Mercury in vaccines].

    PubMed

    Hessel, Luc

    2003-01-01

    Thiomersal, also called thimerosal, is an ethyl mercury derivative used as a preservative to prevent bacterial contamination of multidose vaccine vials after they have been opened. Exposure to low doses of thiomersal has essentially been associated with hypersensitivity reactions. Nevertheless there is no evidence that allergy to thiomersal could be induced by thiomersal-containing vaccines. Allergy to thiomersal is usually of delayed-hypersensitivity type, but its detection through cutaneous tests is not very reliable. Hypersensitivity to thiomersal is not considered as a contraindication to the use of thiomersal-containing vaccines. In 1999 in the USA, thiomersal was present in approximately 30 different childhood vaccines, whereas there were only 2 in France. Although there were no evidence of neurological toxicity in infants related to the use of thiomersal-containing vaccines, the FDA considered that the cumulative dose of mercury received by young infants following vaccination was high enough (although lower than the FDA threshold for methyl mercury) to request vaccine manufacturers to remove thiomersal from vaccine formulations. Since 2002, all childhood vaccines used in Europe and the USA are thiomersal-free or contain only minute amounts of thiomersal. Recently published studies have shown that the mercury levels in the blood, faeces and urine of children who had received thiomersal-containing vaccines were much lower than those accepted by the American Environmental Protection Agency. It has also been demonstrated that the elimination of mercury in children was much faster than what was expected on the basis of studies conducted with methyl mercury originating from food. Recently, the hypothesis that mercury contained in vaccines could be the cause of autism and other neurological developmental disorders created a new debate in the medical community and the general public. To date, none of the epidemiological studies conducted in Europe and elsewhere

  4. Osteoarthritis accelerates and exacerbates Alzheimer's disease pathology in mice

    PubMed Central

    2011-01-01

    Background The purpose of this study was to investigate whether localized peripheral inflammation, such as osteoarthritis, contributes to neuroinflammation and neurodegenerative disease in vivo. Methods We employed the inducible Col1-IL1βXAT mouse model of osteoarthritis, in which induction of osteoarthritis in the knees and temporomandibular joints resulted in astrocyte and microglial activation in the brain, accompanied by upregulation of inflammation-related gene expression. The biological significance of the link between peripheral and brain inflammation was explored in the APP/PS1 mouse model of Alzheimer's disease (AD) whereby osteoarthritis resulted in neuroinflammation as well as exacerbation and acceleration of AD pathology. Results Induction of osteoarthritis exacerbated and accelerated the development of neuroinflammation, as assessed by glial cell activation and quantification of inflammation-related mRNAs, as well as Aβ pathology, assessed by the number and size of amyloid plaques, in the APP/PS1; Col1-IL1βXAT compound transgenic mouse. Conclusion This work supports a model by which peripheral inflammation triggers the development of neuroinflammation and subsequently the induction of AD pathology. Better understanding of the link between peripheral localized inflammation, whether in the form of osteoarthritis, atherosclerosis or other conditions, and brain inflammation, may prove critical to our understanding of the pathophysiology of disorders such as Alzheimer's, Parkinson's and other neurodegenerative diseases. PMID:21899735

  5. Prolonged sleep fragmentation of mice exacerbates febrile responses to lipopolysaccharide

    PubMed Central

    Ringgold, Kristyn M.; Barf, R. Paulien; George, Amrita; Sutton, Blair C.; Opp, Mark R.

    2013-01-01

    Background Sleep disruption is a frequent occurrence in modern society. Whereas many studies have focused on the consequences of total sleep deprivation, few have investigated the condition of sleep disruption. New Method We disrupted sleep of mice during the light period for 9 consecutive days using an intermittently-rotating disc. Results Electroencephalogram (EEG) data demonstrated that non-rapid eye movement (NREM) sleep was severely fragmented and REM sleep was essentially abolished during the 12 h light period. During the dark period, when sleep was not disrupted, neither NREM sleep nor REM sleep times differed from control values. Analysis of the EEG revealed a trend for increased power in the peak frequency of the NREM EEG spectra during the dark period. The fragmentation protocol was not overly stressful as body weights and water consumption remained unchanged, and plasma corticosterone did not differ between mice subjected to 3 or 9 days of sleep disruption and home cage controls. However, mice subjected to 9 days of sleep disruption by this method responded to lipopolysaccharide with an exacerbated febrile response. Comparison with existing methods Existing methods to disrupt sleep of laboratory rodents often subject the animal to excessive locomotion, vibration, or sudden movements. This method does not suffer from any of these confounds. Conclusions This study demonstrates that prolonged sleep disruption of mice exacerbates febrile responses to lipopolysaccharide. This device provides a method to determine mechanisms by which chronic insufficient sleep contributes to the etiology of many pathologies, particularly those with an inflammatory component. PMID:23872243

  6. Geogenic PM₁₀ exposure exacerbates responses to influenza infection.

    PubMed

    Clifford, Holly D; Perks, Kara L; Zosky, Graeme R

    2015-11-15

    Particulate matter (PM) exposure has been linked epidemiologically to exacerbations of lung disease, including respiratory infections. We investigated the effects of geogenic (earth-derived) PM10 (PM<10 μm diameter) on the response to a respiratory viral infection. Geogenic dust was sampled from four communities in arid environments in Western Australia. Adult female BALB/c mice were intranasally exposed to chronic doses of PM10 (10 μg/day for 10 days), and/or infected with influenza (A/Mem/1/71) virus. Inflammation (cells, IL-6, IFN-γ) was measured in bronchoalveolar lavage. Lung mechanics were measured using the forced oscillation technique. Geogenic PM10 induced lung inflammation (neutrophils, macrophages) with additive effects in mice also infected with influenza. PM10 also modified the influenza-induced IL-6 and IFN-γ responses. Geogenic PM10 increased airway resistance, and increased hysteresivity in those exposed to both insults. Viral titres were significantly higher after PM10 exposure. Iron concentration was inversely associated with IFN-γ and positively associated with viral titre and hysteresivity. Geogenic PM10 exposure increases inflammation, impairs lung function and increases viral load, exacerbating the response to respiratory viral infection. Iron in the particles may be a driver of these responses. This has important implications for respiratory health in communities exposed to high geogenic PM10, such as those in arid environments. PMID:26172594

  7. Oxidation pathway and exacerbations in COPD: the role of NAC.

    PubMed

    Matera, Maria Gabriella; Calzetta, Luigino; Cazzola, Mario

    2016-01-01

    Oxidative stress is an important trait in the pathogenesis of chronic obstructive pulmonary disease (COPD). Consequently, targeting oxidative stress is likely to be beneficial as a treatment in COPD. Glutathione (GSH) is an intracellular antioxidant that protects against a variety of different antioxidant species. The increase of lung GSH in COPD is an attempt to counter excess oxidant production but it is inadequate during exacerbations due to the excessive production of ROS. N-acetyl-l-cysteine (NAC) acts as a precursor for the substrate cysteine in synthesis of GSH and also as a mucolytic and anti-inflammatory agent. NAC prevents COPD exacerbations at high dosage (≥1200 mg daily), while a regular treatment with 600 mg daily is enough in chronic bronchitis. Nonetheless, we must still establish whether the level of bronchial obstruction may influence its effects, the effect of high-dose NAC in Caucasian patients with COPD, and the role of NAC in the escalation and de-escalation of therapy in COPD. PMID:26567752

  8. Impact of mild exacerbation on COPD symptoms in a Japanese cohort

    PubMed Central

    Sato, Minako; Chubachi, Shotaro; Sasaki, Mamoru; Haraguchi, Mizuha; Kameyama, Naofumi; Tsutsumi, Akihiro; Takahashi, Saeko; Nakamura, Hidetoshi; Asano, Koichiro; Betsuyaku, Tomoko

    2016-01-01

    Background Patients with COPD might not report mild exacerbation. The frequency, risk factors, and impact of mild exacerbation on COPD status are unknown. Objectives The present study was performed to compare features between mild exacerbation and moderate or severe exacerbation in Japanese patients with COPD. Patients and methods An observational COPD cohort was designed at Keio University and affiliated hospitals to prospectively investigate the management of COPD comorbidities. This study analyzes data only from patients with COPD who had completed annual examinations and questionnaires over a period of 2 years (n=311). Results Among 59 patients with mild exacerbations during the first year, 32.2% also experienced only mild exacerbations in the second year. Among 60 patients with moderate or severe exacerbations during the first year, 40% also had the same severity of exacerbation during the second year. Findings of the COPD assessment test and the symptom component of the St George’s Respiratory Questionnaire at steady state were worse in patients with mild exacerbations than in those who were exacerbation free during the 2-year study period, although the severity of the ratio of predicted forced expiratory volume in 1 second did not differ between them. Severe airflow limitation (the ratio of predicted forced expiratory volume in 1 second <50%) and experience of mild exacerbations independently advanced the likelihood of an elevated COPD assessment test score to ≥2 per year. Conclusion The severity of COPD exacerbation seemed to be temporally stable over 2 years, and even mild exacerbations adversely impacted the health-related quality of life of patients with COPD. PMID:27354785

  9. The Danish vaccination register.

    PubMed

    Grove Krause, T; Jakobsen, S; Haarh, M; Mølbak, K

    2012-01-01

    Immunisation information systems (IIS) are valuable tools for monitoring vaccination coverage and for estimating vaccine effectiveness and safety. Since 2009, an advanced IIS has been developed in Denmark and will be implemented during 2012–14. This IIS is based on a database existing since 2000. The reporting of all administered vaccinations including vaccinations outside the national programme will become mandatory. Citizens will get access to data about their own vaccinations and healthcare personnel will get access to information on the vaccinations of their patients. A national concept of identification, a national solution combining a personal code and a card with codes, ensures easy and secure access to the register. From the outset, the IIS will include data on childhood vaccinations administered from 1996 and onwards. All Danish citizens have a unique identifier, a so called civil registration number, which allows the linking of information on vaccinations coming from different electronic data sources. The main challenge will be to integrate the IIS with the different electronic patient record systems currently existing at general practitioner, vaccination clinic and hospital level thereby avoiding double-entry. A need has been identified for an updated international classification of vaccine products on the market. Such a classification would also be useful for the future exchange of data on immunisations from IIS between countries. PMID:22551494

  10. Nasal vaccine innovation.

    PubMed

    Jabbal-Gill, Inderjit

    2010-12-01

    The current vaccine market is gaining momentum in the development of alternative administration routes namely intranasal, oral, topical, pulmonary, vaginal, and rectal; the nasal route offers the most promising opportunity for vaccine administration. It can enhance convenience, safety, elicit both local and systemic immune responses; thus potentially provide protection from pathogens at the site of entry. Nasal vaccine innovation comes with both opportunities and challenges. The innovative strategies used by industry and researchers to overcome the hurdles are discussed in this article: these include live-attenuated vaccines, adjuvants, mucoadhesives, particulate delivery systems, virus-like particles, vaccine manufacture, challenges of regulatory authorities, and the nasal vaccine impact on market potential. Critical issues for effective nasal vaccination are the antigen-retention period that enables its interaction with the lymphatic system and choice of an adjuvant that is nontoxic and induces the required immune response. Co-adjuvanting by means of a mucoadhesive technology addresses some of these issues. ChiSys(®), a natural bioadhesive with proven intranasal safety profile, has already demonstrated efficacy for several nasally delivered vaccines including norovirus. With the looming threat of a pandemic, alternatives such as intranasal vaccination will ultimately facilitate greater public compliance and rapid mass global vaccination. PMID:21047271

  11. The Meningitis Vaccine Project.

    PubMed

    LaForce, F Marc; Konde, Kader; Viviani, Simonetta; Préziosi, Marie-Pierre

    2007-09-01

    Epidemic meningococcal meningitis is an important public health problem in sub-Saharan Africa. Current control measures rely on reactive immunizations with polysaccharide (PS) vaccines that do not induce herd immunity and are of limited effectiveness in those under 2 years of age. Conversely, polysaccharide conjugate vaccines are effective in infants and have consistently shown an important effect on decreasing carriage, two characteristics that facilitate disease control. In 2001 the Meningitis Vaccine Project (MVP) was created as a partnership between PATH and the World Health Organization (WHO) with the goal of eliminating meningococcal epidemics in Africa through the development, licensure, introduction, and widespread use of conjugate meningococcal vaccines. Since group A Neisseria meningitidis (N. meningitidis) is the dominant pathogen causing epidemic meningitis in Africa MVP is developing an affordable (US$ 0.40 per dose) meningococcal A (Men A) conjugate vaccine through an innovative international partnership that saw transfer of a conjugation and fermentation technology to a developing country vaccine manufacturer. A Phase 1 study of the vaccine in India has shown that the product is safe and immunogenic. Phase 2 studies have begun in Africa, and a large demonstration study of the conjugate vaccine is envisioned for 2008-2009. After extensive consultations with African public health officials a vaccine introduction plan has been developed that includes introduction of the Men A conjugate vaccine into standard Expanded Programme on Immunization (EPI) schedules but also emphasizes mass vaccination of 1-29 years old to induce herd immunity, a strategy that has been shown to be highly effective when the meningococcal C (Men C) conjugate vaccine was introduced in several European countries. The MVP model is a clear example of the usefulness of a "push mechanism" to finance the development of a needed vaccine for the developing world. PMID:17521780

  12. Cutaneous reactions to vaccinations.

    PubMed

    Rosenblatt, Adena E; Stein, Sarah L

    2015-01-01

    Vaccinations are important for infectious disease prevention; however, there are adverse effects of vaccines, many of which are cutaneous. Some of these reactions are due to nonspecific inflammation and irritation at the injection site, whereas other reactions are directly related to the live attenuated virus. Rarely, vaccinations have been associated with generalized hypersensitivity reactions, such as erythema multiforme, Stevens-Johnson syndrome, urticaria, acute generalized exanthematous pustulosis, and drug hypersensitivity syndrome. The onset of certain inflammatory dermatologic conditions, such as lichen planus, granuloma annulare, and pemphigoid, were reported to occur shortly after vaccine administration. Allergic contact dermatitis can develop at the injection site, typically due to adjuvant ingredients in the vaccine, such as thimerosal and aluminum. Vaccinations are important to promote development of both individual and herd immunity. Although most vaccinations are considered relatively safe, there may be adverse effects associated with any vaccine. Cutaneous manifestations make up a large portion of the types of reactions associated with vaccines. There are many different reasons for the development of a cutaneous reaction to a vaccination. Some are directly related to the injection of a live attenuated virus, such as varicella or vaccinia (for immunity to smallpox), whereas others cause more nonspecific erythema and swelling at the injection site, as a result of local inflammation or irritation. Vaccinations have also been associated in rare reports with generalized hypersensitivity reactions, such as erythema multiforme, Stevens-Johnson syndrome, urticaria, acute generalized exanthematous pustulosis, and drug hypersensitivity syndrome. There have been case reports associating the administration of a vaccine with the new onset of a dermatologic condition, such as lichen planus, granuloma annulare, and Sweet syndrome. Finally, allergic contact

  13. Meningitis C vaccine (North American vaccine).

    PubMed

    Lattanzi, Maria; Del Giudice, Giuseppe

    2002-01-01

    North American Vaccine Inc (NAVI) has launched a conjugate polysaccharide vaccinefor the prevention of meningitis caused by group C meningococcal bacteria [433475]. The vaccine is based upon conjugate technology, incorporating the serogroup C polysaccharide (CPS) of all three major serogroups. Antibody-dependent, complement-mediated activity was demonstrated in mice and non-human primates, with no detectable adverse effects [277193]. Approval was filed for in the UK in January 2000 [353305]. In July 2000, Baxter received approval for NeisVac-C in the UK, and by September 2000 the vaccine was expected to be incorporated into the NHS's immunization campaign against meningitis C [381225]. NeisVac-C will initially appear labeled from NAVI; Baxter completed its acquisition of NAVI in June 2000 [375389]. Baxter estimates the worldwide global market for the vaccine at US $600 million per year [376204]. PMID:12054072

  14. VACCINES. A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells.

    PubMed

    Stary, Georg; Olive, Andrew; Radovic-Moreno, Aleksandar F; Gondek, David; Alvarez, David; Basto, Pamela A; Perro, Mario; Vrbanac, Vladimir D; Tager, Andrew M; Shi, Jinjun; Yethon, Jeremy A; Farokhzad, Omid C; Langer, Robert; Starnbach, Michael N; von Andrian, Ulrich H

    2015-06-19

    Genital Chlamydia trachomatis (Ct) infection induces protective immunity that depends on interferon-γ-producing CD4 T cells. By contrast, we report that mucosal exposure to ultraviolet light (UV)-inactivated Ct (UV-Ct) generated regulatory T cells that exacerbated subsequent Ct infection. We show that mucosal immunization with UV-Ct complexed with charge-switching synthetic adjuvant particles (cSAPs) elicited long-lived protection in conventional and humanized mice. UV-Ct-cSAP targeted immunogenic uterine CD11b(+)CD103(-) dendritic cells (DCs), whereas UV-Ct accumulated in tolerogenic CD11b(-)CD103(+) DCs. Regardless of vaccination route, UV-Ct-cSAP induced systemic memory T cells, but only mucosal vaccination induced effector T cells that rapidly seeded uterine mucosa with resident memory T cells (T(RM) cells). Optimal Ct clearance required both T(RM) seeding and subsequent infection-induced recruitment of circulating memory T cells. Thus, UV-Ct-cSAP vaccination generated two synergistic memory T cell subsets with distinct migratory properties. PMID:26089520

  15. Safety of Tdap vaccine in pregnant women: an observational study

    PubMed Central

    Petousis-Harris, Helen; Walls, Tony; Watson, Donna; Paynter, Janine; Graham, Patricia; Turner, Nikki

    2016-01-01

    Objectives Actively recruit and intensively follow pregnant women receiving a dose of acellular pertussis vaccine for 4 weeks after vaccination. Design and settings A prospective observational study conducted in 2 New Zealand regions. Participants Women in their 28th–38th week of pregnancy, recruited from primary care and antenatal clinics at the time of Tdap administration. Telephone interviews were conducted at 48 h and 4 weeks postvaccination. Main outcomes measures Outcomes were injection site reactions, systemic symptoms and serious adverse events (SAEs). Where available, data have been classified and reported according to Brighton Collaboration definitions. Results 793 women participated with 27.9% receiving trivalent inactivated influenza vaccine concomitantly. 79% of participants reported mild or moderate pain and 2.6% severe pain. Any swelling was reported by 7.6%, induration by 12.0% (collected from 1 site only, n=326), and erythema by 5.8% of participants. Fever was reported by 17 (2.1%) participants, 14 of these occurred within 24 h. Headache, dizziness, nausea, myalgia or arthralgia was reported by <4% of participants, respectively, and fatigue by 8.4%. During the study period, there were 115 adverse events in 113 participants, most of which were minor. At the end of the reporting period, 31 events were classified as serious (eg, obstetric bleeding, hypertension, infection, tachycardia, preterm labour, exacerbation of pre-existing condition and pre-eclampsia). All had variable onset time from vaccination. There were two perinatal deaths. Clinician assessment of all SAEs found none likely to be vaccine related. Conclusions Vaccination with Tdap in pregnant women was well tolerated with no SAE likely to be caused by the vaccine. Trial registration number ACTRN12613001045707. PMID:27091823

  16. 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

  17. Recombinant influenza vaccines.

    PubMed

    Sedova, E S; Shcherbinin, D N; Migunov, A I; Smirnov, Iu A; Logunov, D Iu; Shmarov, M M; Tsybalova, L M; Naroditskiĭ, B S; Kiselev, O I; Gintsburg, A L

    2012-10-01

    This review covers the problems encountered in the construction and production of new recombinant influenza vaccines. New approaches to the development of influenza vaccines are investigated; they include reverse genetics methods, production of virus-like particles, and DNA- and viral vector-based vaccines. Such approaches as the delivery of foreign genes by DNA- and viral vector-based vaccines can preserve the native structure of antigens. Adenoviral vectors are a promising gene-delivery platform for a variety of genetic vaccines. Adenoviruses can efficiently penetrate the human organism through mucosal epithelium, thus providing long-term antigen persistence and induction of the innate immune response. This review provides an overview of the practicability of the production of new recombinant influenza cross-protective vaccines on the basis of adenoviral vectors expressing hemagglutinin genes of different influenza strains. PMID:23346377

  18. [Vaccination for international travelers].

    PubMed

    Arrazola, M Pilar; Serrano, Almudena; López-Vélez, Rogelio

    2016-05-01

    Traveler's vaccination is one of the key strategies for the prevention of infectious diseases during international travel. The risk of acquiring an infectious disease is determined in each case by the characteristics of the traveler and the travel, so the pre-departure medical advice of the traveler must be individualized. The World Health Organization classifies travelerś vaccines into three groups. - Vaccines for routine use in national immunization programs: Haemophilus influenzae type b, hepatitis B, polio, measles-mumps-rubella, tetanus-diphtheria-whooping a cough, and chickenpox. - Vaccinations required by law in certain countries before to enter them: yellow fever, meningococcal disease and poliomyelitis. - Vaccines recommended depending on the circumstances: cholera, japanese encephalitis, tick-borne encephalitis, meningococcal disease, typhoid fever, influenza, hepatitis A, hepatitis B, rabies and BCG. This review is intended to introduce the reader to the field of international vaccination. PMID:26920587

  19. Vaccines against leptospirosis.

    PubMed

    Adler, Ben

    2015-01-01

    Vaccines against leptospirosis followed within a year of the first isolation of Leptospira, with the first use of a killed whole cell bacterin vaccine in guinea pigs published in 1916. Since then, bacterin vaccines have been used in humans, cattle, swine, and dogs and remain the only vaccines licensed at the present time. The immunity elicited is restricted to serovars with related lipopolysaccharide (LPS) antigen. Likewise, vaccines based on LPS antigens have clearly demonstrated protection in animal models, which is also at best serogroup specific. The advent of leptospiral genome sequences has allowed a reverse vaccinology approach for vaccine development. However, the use of inadequate challenge doses and inappropriate statistical analysis invalidates many of the claims of protection with recombinant proteins. PMID:25388138

  20. Chikungunya vaccines in development

    PubMed Central

    Schwameis, Michael; Buchtele, Nina; Wadowski, Patricia Pia; Schoergenhofer, Christian; Jilma, Bernd

    2016-01-01

    ABSTRACT Chikungunya virus has become a global health threat, spreading to the industrial world of Europe and the Americas; no treatment or prophylactic vaccine is available. Since the late 1960s much effort has been put into the development of a vaccine, and several heterogeneous strategies have already been explored. Only two candidates have recently qualified to enter clinical phase II trials, a chikungunya virus-like particle-based vaccine and a recombinant live attenuated measles virus-vectored vaccine. This review focuses on the current status of vaccine development against chikungunya virus in humans and discusses the diversity of immunization strategies, results of recent human trials and promising vaccine candidates. PMID:26554522

  1. What Vaccinations Do You Need?

    MedlinePlus

    ... Newsroom Contact Us You are here Home » What Vaccinations Do You Need? A Guide for Adults with ... a Kidney Transplant Why do I need a vaccination? Vaccinations, usually given as a shot, protect you ...

  2. Vaccine Treatment for Prostate Cancer

    MedlinePlus

    ... Preventing and treating prostate cancer spread to bones Vaccine treatment for prostate cancer Sipuleucel-T (Provenge) is ... less advanced prostate cancer. Possible side effects of vaccine treatment Side effects from the vaccine tend to ...

  3. What Vaccines Do You Need?

    MedlinePlus

    ... Why Immunize? Vaccines: The Basics Adolescent and Adult Vaccine Quiz Recommend on Facebook Tweet Share Compartir Españ ... adolescentes y adultos Did you know that certain vaccines are recommended for adults and adolescents?* Take this ...

  4. Renal Disease and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals Renal Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  5. Diphtheria Vaccination: Who Needs It?

    MedlinePlus

    ... and adults - Tetanus-diphtheria-acellular Pertussis vaccine Diphtheria Vaccination: Who Needs It? Recommend on Facebook Tweet Share ... need this vaccine? Yes, the Advisory Committee on Immunization Practices (ACIP) recommends 5 doses of diphtheria and ...

  6. Liver Disease and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  7. HIV Infection and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals HIV Infection and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... percentage is less than 15%. Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  8. New technologies for influenza vaccines.

    PubMed

    Dormitzer, Philip R; Tsai, Theodore F; Del Giudice, Giuseppe

    2012-01-01

    Influenza vaccine preparations have been administered to humans since the late 1930s, and the diversity of approaches in licensed trivalent seasonal or monovalent pandemic products is unparalleled by vaccines against any other target. These approaches include inactivated whole virus vaccines, detergent or solvent "split" vaccines, subunit vaccines, live attenuated vaccines, adjuvanted vaccines, intramuscular vaccines, intradermal vaccines, intranasal vaccines, egg-produced vaccines and mammalian cell culture-produced vaccines. The challenges of influenza immunization, including multiple co-circulating strains, antigenic change over time, a broad age spectrum of disease, and the threat of pandemics, continue to drive the development of new approaches. This review describes some of the new approaches to influenza immunization that are the subjects of active research and development. PMID:22251994

  9. Biomarkers that predict and guide therapy for exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Brightling, C E

    2013-12-01

    Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. COPD exacerbations have a major impact on morbidity and mortality. The etiology of COPD exacerbations is largely due to viral and bacterial infections in combination with underlying inflammation that is typically neutrophilic, although it is eosinophilic in 10 to 25% of cases. We review the recent studies that have defined novel biological clusters at exacerbation events and consequently identified important biomarkers to direct therapy. These biomarkers include C-reactive protein, procalcitonin, and peripheral blood eosinophil count, which are readily available. We are therefore at a point of making personalized antibiotic and corticosteroid therapy in COPD exacerbations a reality. Integration of the wealth of emerging data to further define the complexity of exacerbations also promises to identify new targets and biomarkers to treat COPD exacerbations. PMID:24313775

  10. Japanese Encephalitis Vaccines

    PubMed Central

    McArthur, Monica A.; Holbrook, Michael R.

    2012-01-01

    Japanese encephalitis (JE) is a significant human health concern in Asia, Indonesia and parts of Australia with more than 3 billion people potentially at risk of infection with Japanese encephalitis virus (JEV), the causative agent of JE. Given the risk to human health and the theoretical potential for JEV use as a bioweapon, the development of safe and effective vaccines to prevent JEV infection is vital for preserving human health. The development of vaccines for JE began in the 1940s with formalin-inactivated mouse brain-derived vaccines. These vaccines have been shown to induce a protective immune response and to be very effective. Mouse brain-derived vaccines were still in use until May 2011 when the last lots of the BIKEN® JE-VAX® expired. Development of modern JE vaccines utilizes cell culture-derived viruses and improvements in manufacturing processes as well as removal of potential allergens or toxins have significantly improved vaccine safety. China has developed a live-attenuated vaccine that has proven to induce protective immunity following a single inoculation. In addition, a chimeric vaccine virus incorporating the prM and E structural proteins derived from the live-attenuated JE vaccine into the live-attenuated yellow fever 17D vaccine virus backbone is currently in clinical trials. In this article, we provide a summary of JE vaccine development and on-going clinical trials. We also discuss the potential risk of JEV as a bioweapon with a focus on virus sustainability if used as a weapon. PMID:23125946

  11. [Does vaccination cause disease?].

    PubMed

    Zingg, W

    2005-10-01

    Not many inventions in medical history have influenced our society as much as vaccination. The concept is old and simple. When Edward Jenner published his work on cowpox, "variolation" was quite common. In this procedure, pus of patients with mild smallpox was transferred to healthy individuals. Meanwhile smallpox has been eradicated worldwide. Diseases such as poliomyelitis, diphtheria or tetanus almost disappeared in industrialized countries. The same happened with epiglottitis and meningitis due to Haemophilus influenzae type b (Hib) after vaccination against Hib was introduced in Switzerland in 1990. This success was possible because of routine vaccination. Immunization is a save procedure and adverse events are much lower than complications in the natural course of the prevented diseases. However vaccinations were accused to cause diseases themselves such as asthma, multiple sclerosis, diabetes mellitus, chronic arthritis or autism. Hitherto no large cohort study or case-control-study was able to proof responsibility of vaccines in any of these diseases. Public media are eager to publish early data from surveillance reports or case reports which are descriptive and never a principle of cause and effect. In large controlled trials there was no proof that vaccination causes asthma, hepatitis-B-vaccination causes multiple sclerosis or macrophagic myofasciitis, Hib-vaccination causes diabetes mellitus, rubella-vaccination causes chronic arthritis, measles-mumps-rubella-vaccination causes gait disturbance or thiomersal causes autism. These results are rarely published in newspapers or television. Thus, many caring parents are left with negative ideas about immunization. Looking for the best for their children they withhold vaccination and give way to resurgence of preventable diseases in our communities. This must be prevented. There is more evidence than expected that vaccination is safe and this can and must be told to parents. PMID:16277033

  12. Emerging Vaccine Technologies

    PubMed Central

    Loomis, Rebecca J.; Johnson, Philip R.

    2015-01-01

    Vaccination has proven to be an invaluable means of preventing infectious diseases by reducing both incidence of disease and mortality. However, vaccines have not been effectively developed for many diseases including HIV-1, hepatitis C virus (HCV), tuberculosis and malaria, among others. The emergence of new technologies with a growing understanding of host-pathogen interactions and immunity may lead to efficacious vaccines against pathogens, previously thought impossible. PMID:26343196

  13. Vaccines for Drug Abuse

    PubMed Central

    Shen, Xiaoyun; Orson, Frank M.; Kosten, Thomas R.

    2012-01-01

    Current medications for drug abuse have had only limited success. Anti-addiction vaccines to elicit antibodies that block the pharmacological effects of drugs have great potential for treating drug abuse. We review the status for two vaccines that are undergoing clinical trials (cocaine and nicotine) and two that are still in pre-clinical development (methamphetamine and heroin). We also outline the challenges and ethical concerns for anti-addiction vaccine development and their use as future therapeutics. PMID:22130115

  14. Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909.

    PubMed

    Speiser, Daniel E; Liénard, Danielle; Rufer, Nathalie; Rubio-Godoy, Verena; Rimoldi, Donata; Lejeune, Ferdy; Krieg, Arthur M; Cerottini, Jean-Charles; Romero, Pedro

    2005-03-01

    The induction of potent CD8+ T cell responses by vaccines to fight microbes or tumors remains a major challenge, as many candidates for human vaccines have proved to be poorly immunogenic. Deoxycytidyl-deoxyguanosin oligodeoxynucleotides (CpG ODNs) trigger Toll-like receptor 9, resulting in dendritic cell maturation that can enhance immunogenicity of peptide-based vaccines in mice. We tested whether a synthetic ODN, CpG 7909, could improve human tumor antigen-specific CD8+ T cell responses. Eight HLA-A2+ melanoma patients received 4 monthly vaccinations of low-dose CpG 7909 mixed with melanoma antigen A (Melan-A; identical to MART-1) analog peptide and incomplete Freund's adjuvant. All patients exhibited rapid and strong antigen-specific T cell responses: the frequency of Melan-A-specific T cells reached over 3% of circulating CD8+ T cells. This was one order of magnitude higher than the frequency seen in 8 control patients treated similarly but without CpG and 1-3 orders of magnitude higher than that seen in previous studies with synthetic vaccines. The enhanced T cell populations consisted primarily of effector memory cells, which in part secreted IFN- and expressed granzyme B and perforin ex vivo. In vitro, T cell clones recognized and killed melanoma cells in an antigen-specific manner. Thus, CpG 7909 is an efficient vaccine adjuvant that promotes strong antigen-specific CD8+ T cell responses in humans. PMID:15696196

  15. Dengue virus vaccine development.

    PubMed

    Yauch, Lauren E; Shresta, Sujan

    2014-01-01

    Dengue virus (DENV) is a significant cause of morbidity and mortality in tropical and subtropical regions, causing hundreds of millions of infections each year. Infections range from asymptomatic to a self-limited febrile illness, dengue fever (DF), to the life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). The expanding of the habitat of DENV-transmitting mosquitoes has resulted in dramatic increases in the number of cases over the past 50 years, and recent outbreaks have occurred in the United States. Developing a dengue vaccine is a global health priority. DENV vaccine development is challenging due to the existence of four serotypes of the virus (DENV1-4), which a vaccine must protect against. Additionally, the adaptive immune response to DENV may be both protective and pathogenic upon subsequent infection, and the precise features of protective versus pathogenic immune responses to DENV are unknown, complicating vaccine development. Numerous vaccine candidates, including live attenuated, inactivated, recombinant subunit, DNA, and viral vectored vaccines, are in various stages of clinical development, from preclinical to phase 3. This review will discuss the adaptive immune response to DENV, dengue vaccine challenges, animal models used to test dengue vaccine candidates, and historical and current dengue vaccine approaches. PMID:24373316

  16. Rabies vaccines and interferon

    PubMed Central

    Turner, G. S.

    1972-01-01

    Samples of Fermi, Semple, modified Semple, Duck embryo and tissue culture rabies vaccine were inoculated by different routes and in different doses into rabbits, mice and hamsters. The vaccines induced neither detectable interferon nor immediate protection against lethal challenge with CVS rabies virus. Under similar conditions, high but transient levels of interferon were induced in control animals of the same species with the polynucleotide complex Poly I.C. Hamsters but not mice were protected by Poly I.C.-induced interferon. No autointerference by vaccine with challenge virus was established. Vaccine-induced protection in mice was directly related to immune response. PMID:4506993

  17. Polyvalent AIDS Vaccines

    PubMed Central

    Lu, Shan; Grimes Serrano, Jill M.; Wang, Shixia

    2013-01-01

    A major hurdle in the development of a global HIV-1 vaccine is viral diversity. For close to three decades, HIV vaccine development has focused on either the induction of T cell immune responses or antibody responses, and only rarely on both components. After the failure of the STEP trial, the scientific community concluded that a T cell-based vaccine would likely not be protective if the T cell immune responses were elicited against only a few dominant epitopes. Similarly, for vaccines focusing on antibody responses, one of the main criticisms after VaxGen’s failed Phase III trials was on the limited antigen breadth included in the two formulations used. The successes of polyvalent vaccine approaches against other antigenically variable pathogens encourage implementation of the same approach for the design of HIV-1 vaccines. A review of the existing HIV-1 vaccination approaches based on the polyvalent principle is included here to provide a historical perspective for the current effort of developing a polyvalent HIV-1 vaccine. Results summarized in this review provide a clear indication that the polyvalent approach is a viable one for the future development of an effective HIV vaccine. PMID:21054250

  18. Cochlear-Meningitis Vaccination

    MedlinePlus

    ... and otolaryngologists) and families should review the vaccination records of current and prospective cochlear implant recipients to ensure that all ... of Use Join Donate ENTConnect Contact Us ...

  19. Vaccines: the Fourth Century▿

    PubMed Central

    Plotkin, Stanley A.

    2009-01-01

    Vaccine development, which began with Edward Jenner's observations in the late 18th century, has entered its 4th century. From its beginnings, with the use of whole organisms that had been weakened or inactivated, to the modern-day use of genetic engineering, it has taken advantage of the tools discovered in other branches of microbiology. Numerous successful vaccines are in use, but the list of diseases for which vaccines do not exist is long. However, the multiplicity of strategies now available, discussed in this article, portends even more successful development of vaccines. PMID:19793898

  20. Anthrax vaccination strategies

    PubMed Central

    Cybulski, Robert J.; Sanz, Patrick; O'Brien, Alison D.

    2009-01-01

    The biological attack conducted through the U.S. postal system in 2001 broadened the threat posed by anthrax from one pertinent mainly to soldiers on the battlefield to one understood to exist throughout our society. The expansion of the threatened population placed greater emphasis on the reexamination of how we vaccinate against Bacillus anthracis. The currently-licensed Anthrax Vaccine, Adsorbed (AVA) and Anthrax Vaccine, Precipitated (AVP) are capable of generating a protective immune response but are hampered by shortcomings that make their widespread use undesirable or infeasible. Efforts to gain U.S. Food and Drug Administration (FDA) approval for licensure of a second generation recombinant protective antigen (rPA)-based anthrax vaccine are ongoing. However, this vaccine's reliance on the generation of a humoral immune response against a single virulence factor has led a number of scientists to conclude that the vaccine is likely not the final solution to optimal anthrax vaccine design. Other vaccine approaches, which seek a more comprehensive immune response targeted at multiple components of the B. anthracis organism, are under active investigation. This review seeks to summarize work that has been done to build on the current PA-based vaccine methodology and to evaluate the search for future anthrax prophylaxis strategies. PMID:19729034

  1. Vaccine delivery using nanoparticles

    PubMed Central

    Gregory, Anthony E.; Titball, Richard; Williamson, Diane

    2013-01-01

    Vaccination has had a major impact on the control of infectious diseases. However, there are still many infectious diseases for which the development of an effective vaccine has been elusive. In many cases the failure to devise vaccines is a consequence of the inability of vaccine candidates to evoke appropriate immune responses. This is especially true where cellular immunity is required for protective immunity and this problem is compounded by the move toward devising sub-unit vaccines. Over the past decade nanoscale size (<1000 nm) materials such as virus-like particles, liposomes, ISCOMs, polymeric, and non-degradable nanospheres have received attention as potential delivery vehicles for vaccine antigens which can both stabilize vaccine antigens and act as adjuvants. Importantly, some of these nanoparticles (NPs) are able to enter antigen-presenting cells by different pathways, thereby modulating the immune response to the antigen. This may be critical for the induction of protective Th1-type immune responses to intracellular pathogens. Their properties also make them suitable for the delivery of antigens at mucosal surfaces and for intradermal administration. In this review we compare the utilities of different NP systems for the delivery of sub-unit vaccines and evaluate the potential of these delivery systems for the development of new vaccines against a range of pathogens. PMID:23532930

  2. Vaccines, our shared responsibility.

    PubMed

    Pagliusi, Sonia; Jain, Rishabh; Suri, Rajinder Kumar

    2015-05-01

    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. PMID:25749248

  3. Molecular basis of vaccination.

    PubMed

    Del Giudice, G; Pizza, M; Rappuoli, R

    1998-02-01

    Vaccines represent the most cost-effective means to prevent infectious diseases. Most of the vaccines which are currently available were developed long before the era of molecular biology and biotechnology. They were obtained following empirical approaches leading to the inactivation or to the attenuation of microorganisms, without any knowledge neither of the mechanisms of pathogenesis of the disease they were expected to protect from, nor of the immune responses elicited by the infectious agents or by the vaccine itself. The past two decades have seen an impressive progress in the field of immunology and molecular biology, which have allowed a better understanding of the interactions occurring between microbes and their hosts. This basic knowledge has represented an impetus towards the generation of better vaccines and the development of new vaccines. In this monograph we briefly summarize some of the most important biotechnological approaches that are currently followed in the development of new vaccines, and provide details on an approach to vaccine development: the genetic detoxification of bacterial toxins. Such an approach has been particularly successful in the rational design of a new vaccine against pertussis, which has been shown to be extremely efficacious and safe. It has been applied to the construction of powerful mucosal adjuvants, for administration of vaccines at mucosal surfaces. PMID:9789264

  4. Tetanus, Diphtheria, Pertussis (Tdap) Vaccine

    MedlinePlus

    Adacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Boostrix® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

  5. Monitoring asthma in childhood: symptoms, exacerbations and quality of life.

    PubMed

    Brand, Paul L P; Mäkelä, Mika J; Szefler, Stanley J; Frischer, Thomas; Price, David

    2015-06-01

    Monitoring asthma in children in clinical practice is primarily performed by reviewing disease activity (daytime and night-time symptoms, use of reliever medication, exacerbations requiring frequent use of reliever medication and urgent visits to the healthcare professional) and the impact of the disease on children's daily activities, including sports and play, in a clinical interview. In such an interview, most task force members also discuss adherence to maintenance therapy and the patients' (and parents') views and beliefs on the goals of treatment and the amount of treatment required to achieve those goals. Composite asthma control and quality of life measures, although potentially useful in research, have limited value in clinical practice because they have a short recall window and do not cover the entire spectrum of asthma control. Telemonitoring of children with asthma cannot replace face-to-face follow-up and monitoring because there is no evidence that it is associated with improved health outcomes. PMID:26028631

  6. A20-Deficient Mast Cells Exacerbate Inflammatory Responses In Vivo

    PubMed Central

    Vahl, J. Christoph; Aszodi, Attila; Peschke, Katrin; Schenten, Dominik; Hammad, Hamida; Beyaert, Rudi; Saur, Dieter; van Loo, Geert; Roers, Axel; Lambrecht, Bart N.; Kool, Mirjam; Schmidt-Supprian, Marc

    2014-01-01

    Mast cells are implicated in the pathogenesis of inflammatory and autoimmune diseases. However, this notion based on studies in mast cell-deficient mice is controversial. We therefore established an in vivo model for hyperactive mast cells by specifically ablating the NF-κB negative feedback regulator A20. While A20 deficiency did not affect mast cell degranulation, it resulted in amplified pro-inflammatory responses downstream of IgE/FcεRI, TLRs, IL-1R, and IL-33R. As a consequence house dust mite- and IL-33-driven lung inflammation, late phase cutaneous anaphylaxis, and collagen-induced arthritis were aggravated, in contrast to experimental autoimmune encephalomyelitis and immediate anaphylaxis. Our results provide in vivo evidence that hyperactive mast cells can exacerbate inflammatory disorders and define diseases that might benefit from therapeutic intervention with mast cell function. PMID:24453940

  7. [Etiological and exacerbation factors for COPD. Body weight loss].

    PubMed

    Yokoyama, Akihito

    2016-05-01

    Hunger or malnutrition is not only a historical issue but also a current problem worldwide. Biological responses to hunger are evolutionary prepared in our body, including energy generation by degradation of body proteins. Extreme weight loss (malnutrition) can cause air space enlargement in human and rodents. However, the changes in rodents could be reversible, since refeeding could repair the pathology. On the other hand, weight loss is a common feature in patients with more severe COPD. Complex factors, such as increased energy consumption, decreased food uptake by low grade inflammation, socio-economic factors and so on, are involved in weight loss. Weight loss in patients with COPD also increases the risk of exacerbation, hospitalization, and death. PMID:27254941

  8. Molecular and clinical diseasome of comorbidities in exacerbated COPD patients.

    PubMed

    Faner, Rosa; Gutiérrez-Sacristán, Alba; Castro-Acosta, Ady; Grosdidier, Solène; Gan, Wenqi; Sánchez-Mayor, Milagros; Lopez-Campos, Jose Luis; Pozo-Rodriguez, Francisco; Sanz, Ferran; Mannino, David; Furlong, Laura I; Agusti, Alvar

    2015-10-01

    The frequent occurrence of comorbidities in patients with chronic obstructive pulmonary disease (COPD) suggests that they may share pathobiological processes and/or risk factors.To explore these possibilities we compared the clinical diseasome and the molecular diseasome of 5447 COPD patients hospitalised because of an exacerbation of the disease. The clinical diseasome is a network representation of the relationships between diseases, in which diseases are connected if they co-occur more than expected at random; in the molecular diseasome, diseases are linked if they share associated genes or interaction between proteins.The results showed that about half of the disease pairs identified in the clinical diseasome had a biological counterpart in the molecular diseasome, particularly those related to inflammation and vascular tone regulation. Interestingly, the clinical diseasome of these patients appears independent of age, cumulative smoking exposure or severity of airflow limitation.These results support the existence of shared molecular mechanisms among comorbidities in COPD. PMID:26250499

  9. Does aspirin-induced oxidative stress cause asthma exacerbation?

    PubMed Central

    Kacprzak, Dorota

    2015-01-01

    Aspirin-induced asthma (AIA) is a distinct clinical syndrome characterized by severe asthma exacerbations after ingestion of aspirin or other non-steroidal anti-inflammatory drugs. The exact pathomechanism of AIA remains unknown, though ongoing research has shed some light. Recently, more and more attention has been focused on the role of aspirin in the induction of oxidative stress, especially in cancer cell systems. However, it has not excluded the similar action of aspirin in other inflammatory disorders such as asthma. Moreover, increased levels of 8-isoprostanes, reliable biomarkers of oxidative stress in expired breath condensate in steroid-naïve patients with AIA compared to AIA patients treated with steroids and healthy volunteers, has been observed. This review is an attempt to cover aspirin-induced oxidative stress action in AIA and to suggest a possible related pathomechanism. PMID:26170841

  10. Non-invasive ventilation in exacerbations of COPD

    PubMed Central

    Ambrosino, Nicolino; Vagheggini, Guido

    2007-01-01

    Randomized controlled trials have confirmed the evidence and helped to define when and where non invasive mechanical ventilation (NIV) should be the first line treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Noninvasive ventilation has its best indication in moderate-to-severe respiratory acidosis in patients with AECOPD. For this indication, studies conducted in ICU, in wards and in accident and emergency departments confirmed its effectiveness in preventing endotracheal intubation and reducing mortality. The skill of the health care team promotes proper NIV utilization and improves the patient outcome. Patients with severe acidosis or with altered levels of consciousness due to hypercapnic acute respiratory failure are exposed to high risk of NIV failure. In these patients a NIV trial may be attempted in closely monitored clinical settings where prompt endotracheal intubation may be assured. PMID:18268921

  11. Fine particulate matter in acute exacerbation of COPD.

    PubMed

    Ni, Lei; Chuang, Chia-Chen; Zuo, Li

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a common airway disorder. In particular, acute exacerbations of COPD (AECOPD) can significantly reduce pulmonary function. The majority of AECOPD episodes are attributed to infections, although environmental stress also plays a role. Increasing urbanization and associated air pollution, especially in developing countries, have been shown to contribute to COPD pathogenesis. Elevated levels of particulate matter (PM) in polluted air are strongly correlated with the onset and development of various respiratory diseases. In this review, we have conducted an extensive literature search of recent studies of the role of PM2.5 (fine PM) in AECOPD. PM2.5 leads to AECOPD via inflammation, oxidative stress (OS), immune dysfunction, and altered airway epithelial structure and microbiome. Reducing PM2.5 levels is a viable approach to lower AECOPD incidence, attenuate COPD progression and decrease the associated healthcare burden. PMID:26557095

  12. Fine particulate matter in acute exacerbation of COPD

    PubMed Central

    Ni, Lei; Chuang, Chia-Chen; Zuo, Li

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a common airway disorder. In particular, acute exacerbations of COPD (AECOPD) can significantly reduce pulmonary function. The majority of AECOPD episodes are attributed to infections, although environmental stress also plays a role. Increasing urbanization and associated air pollution, especially in developing countries, have been shown to contribute to COPD pathogenesis. Elevated levels of particulate matter (PM) in polluted air are strongly correlated with the onset and development of various respiratory diseases. In this review, we have conducted an extensive literature search of recent studies of the role of PM2.5 (fine PM) in AECOPD. PM2.5 leads to AECOPD via inflammation, oxidative stress (OS), immune dysfunction, and altered airway epithelial structure and microbiome. Reducing PM2.5 levels is a viable approach to lower AECOPD incidence, attenuate COPD progression and decrease the associated healthcare burden. PMID:26557095

  13. [Etiological and exacerbation factors for COPD. Air pollution].

    PubMed

    Ogawa, Kazumasa; Kishi, Kazuma

    2016-05-01

    Recently, it has been found that the number of patients with chronic obstructive pulmonary disease (COPD) who do not have a history of smoking is higher than expected, and a number of factors affect the development of COPD. Although adequate evidence for the relation of ambient air pollution, including the presence of particulate matter (PM2.5), with the development of COPD is lacking, higher mortality from respiratory and cardiovascular diseases has been reported among patients exposed to air pollution for a long time. In addition, several reports have pointed out the possibility that acute exacerbation of COPD can be caused by short-term exposure to air pollution. Tobacco smoke is the main cause of highly concentrated PM2.5 indoors, and second hand smoke is related with the development of COPD and the high mortality from COPD. In developing countries, biomass fuel combustion contributes to COPD, especially among housewives who do not smoke. PMID:27254939

  14. Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology

    SciTech Connect

    Schneider, Brent C.; Constant, Stephanie L.; Patierno, Steven R.; Jurjus, Rosalyn A.; Ceryak, Susan M.

    2012-02-15

    Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. -- Highlights: ► Allergic asthma correlated with exposure to certain inhaled particulate chromates. ► Direct causal association between Cr(VI) and allergic asthma not established. ► Cr exacerbated pathology and airway hyperresponsiveness in an OVA-challenged mouse. ► Particulate Cr

  15. Predicting Healthcare Utilization by Patients Admitted for COPD Exacerbation

    PubMed Central

    Kaza, Anupama Murthy; Balasubramanian, Nithilavalli; Chandrasekaran, Siddhuraj

    2016-01-01

    Background Healthcare utilization, especially length of hospital stay and ICU admission, for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) determine overall outcomes in terms of morbidity, mortality and cost burden. Predicting prolonged hospital stay (PHS) and prolonged intensive care (PIC) for AECOPD is useful for rational allocation of resources in healthcare centres. Aim To characterize the pattern of healthcare utilization by COPD patients hospitalized for acute exacerbation, and to identify clinical and laboratory predictors of ‘prolonged hospital stay’ (PHS) and ‘prolonged intensive care’(PIC) Materials and Methods This study attempted through retrospective data analysis, to identify risk factors and evolve prediction models for increased healthcare utilization namely PHS and PIC for AECOPD. The data were extracted from 255 eligible admissions for AECOPD by 166 patients from Aug 2012 to July 2013. Logistic regression analysis was used for identifying predictors and models were tested with area under receiver operating characteristic curve. Results Independent predictors of prolonged hospital stay (≥ 6 days) were chronic respiratory failure at baseline, low saturation at admission, high HbA1c level and positive isolates in sputum culture. Independent predictors of prolonged intensive care (for ≥ 48 hours) were past history of pulmonary tuberculosis, chronic respiratory failure at baseline, low saturation at admission, high leukocyte count and positive culture isolates in sputum. Prediction models evolved from variables available at admission showed AUC 0.805 (95% CI 0.729 – 0.881) and 0.825 (95% CI 0.75 – 0.90) for PHS and ICU admissions respectively. Conclusion Our prediction models derived from simple and easily available variables show good discriminative properties in predicting PHS and PIC for AECOPD. When prospectively validated, these models are useful for rational allocation of services especially in resource

  16. IL-33 Exacerbates Periodontal Disease through Induction of RANKL.

    PubMed

    Malcolm, J; Awang, R A; Oliver-Bell, J; Butcher, J P; Campbell, L; Adrados Planell, A; Lappin, D F; Fukada, S Y; Nile, C J; Liew, F Y; Culshaw, S

    2015-07-01

    Cytokines mediate the balance between protective and destructive immunity in periodontitis. We sought to investigate the role of IL-33 in periodontitis. The expression of IL-33 in gingival tissue from healthy controls (n = 10) and patients with chronic periodontitis (n = 17) was investigated. Based on a murine model of periodontal disease, the function of IL-33 was determined first by administration of exogenous IL-33 and second by inhibition of IL-33 signaling using mice deficient in the IL-33 receptor ST2. Alveolar bone level, serum antibody, and lymphocyte responses were assessed in the murine model. Expression of IL-33 and ST2 was elevated in gingival tissues from patients with chronic periodontitis as compared with healthy tissues (P < 0.05). Similarly, Il33 expression was higher in periodontal tissues of Porphyromonas gingivalis-infected mice as compared with sham-infected controls (P < 0.05). IL-33 treatment of P. gingivalis-infected mice significantly exacerbated alveolar bone loss when compared with infection or IL-33 treatment alone (P < 0.001). Conversely, P. gingivalis infection-induced alveolar bone loss was attenuated in mice lacking ST2. The percentages of T and B lymphocytes expressing nuclear factor κB ligand (RANKL) in the gingival tissues and T lymphocytes expressing RANKL in the cervical draining lymph nodes were higher in IL-33-treated P. gingivalis-infected mice versus phosphate buffered saline-treated P. gingivalis-infected controls (all P < 0.001). Targeting the RANKL pathway by osteoprotegerin administration abrogated periodontal bone destruction in P. gingivalis-infected, IL-33-treated mice. These data demonstrate a previously unrecognized role for IL-33 in exacerbating bone loss in a RANKL-dependent manner in the context of bacterial infection and suggest that this pathway may be amenable to manipulation as a novel therapeutic target in periodontitis. PMID:25808546

  17. Soluble CD93 as a Novel Biomarker in Asthma Exacerbation

    PubMed Central

    Jalili, Ali; Mahdawi, Laili; Ghaderi, Ebrahim; Shilan, Mohammadi

    2016-01-01

    Asthma research is shifting from studying symptoms and lung functions to the narrow-focus cellular profiles protein analysis, biomarkers, and genetic markers. The transmembrane glycoprotein CD93 is involved in endothelial cell migration, angiogenesis, leukocytes extravasation, apoptosis, innate immunity and inflammation. Relationships between the serum level of soluble CD93 (sCD93) and acute myocardial infarction/premature MI/inflammatory arthritis/skin sclerosis have recently been reported. We hypothesized that sCD93 would be elevated during the acute phase of asthma. We measured the serum level of sCD93 in 57 patients with asthma exacerbation and 57 age-and gender-matched healthy controls. Additionally, sCD93 was reassessed at the time of discharge from the hospital. Clinical characteristics and peak expiratory flow (PEF) of the patients were assessed. The primary outcome was the comparison of serum level of sCD93 between asthmatics and healthy subjects. The sCD93 values ranged from 128 to 789 ng/mL in asthmatics (345.83±115.81) and from 31 to 289 ng/mL in control subjects (169.46±62.43). The difference between the 2 groups was statistically significant (P<0.001). The association between sCD93 and asthma remained significant after adjusting for age, sex, and BMI. The differences between asthmatics and controls remained significant on the last day of hospital stay. The association between sCD93 and PEF was not significant. In conclusion, the serum level of soluble CD93 is increased in patients with asthma exacerbation. It also showed that serum levels of sCD93 decreased with treatment of asthma attack. The clinical usefulness of determination of sCD93 as a biomarker of asthma requires further studies. PMID:27334785

  18. Soluble CD93 as a Novel Biomarker in Asthma Exacerbation.

    PubMed

    Sigari, Naseh; Jalili, Ali; Mahdawi, Laili; Ghaderi, Ebrahim; Shilan, Mohammadi

    2016-09-01

    Asthma research is shifting from studying symptoms and lung functions to the narrow-focus cellular profiles protein analysis, biomarkers, and genetic markers. The transmembrane glycoprotein CD93 is involved in endothelial cell migration, angiogenesis, leukocytes extravasation, apoptosis, innate immunity and inflammation. Relationships between the serum level of soluble CD93 (sCD93) and acute myocardial infarction/premature MI/inflammatory arthritis/skin sclerosis have recently been reported. We hypothesized that sCD93 would be elevated during the acute phase of asthma. We measured the serum level of sCD93 in 57 patients with asthma exacerbation and 57 age-and gender-matched healthy controls. Additionally, sCD93 was reassessed at the time of discharge from the hospital. Clinical characteristics and peak expiratory flow (PEF) of the patients were assessed. The primary outcome was the comparison of serum level of sCD93 between asthmatics and healthy subjects. The sCD93 values ranged from 128 to 789 ng/mL in asthmatics (345.83±115.81) and from 31 to 289 ng/mL in control subjects (169.46±62.43). The difference between the 2 groups was statistically significant (P<0.001). The association between sCD93 and asthma remained significant after adjusting for age, sex, and BMI. The differences between asthmatics and controls remained significant on the last day of hospital stay. The association between sCD93 and PEF was not significant. In conclusion, the serum level of soluble CD93 is increased in patients with asthma exacerbation. It also showed that serum levels of sCD93 decreased with treatment of asthma attack. The clinical usefulness of determination of sCD93 as a biomarker of asthma requires further studies. PMID:27334785

  19. Universal influenza vaccines: Shifting to better vaccines.

    PubMed

    Berlanda Scorza, Francesco; Tsvetnitsky, Vadim; Donnelly, John J

    2016-06-01

    Influenza virus causes acute upper and lower respiratory infections and is the most likely, among known pathogens, to cause a large epidemic in humans. Influenza virus mutates rapidly, enabling it to evade natural and vaccine-induced immunity. Furthermore, influenza viruses can cross from animals to humans, generating novel, potentially pandemic strains. Currently available influenza vaccines induce a strain specific response and may be ineffective against new influenza viruses. The difficulty in predicting circulating strains has frequently resulted in mismatch between the annual vaccine and circulating viruses. Low-resource countries remain mostly unprotected against seasonal influenza and are particularly vulnerable to future pandemics, in part, because investments in vaccine manufacturing and stockpiling are concentrated in high-resource countries. Antibodies that target conserved sites in the hemagglutinin stalk have been isolated from humans and shown to confer protection in animal models, suggesting that broadly protective immunity may be possible. Several innovative influenza vaccine candidates are currently in preclinical or early clinical development. New technologies include adjuvants, synthetic peptides, virus-like particles (VLPs), DNA vectors, messenger RNA, viral vectors, and attenuated or inactivated influenza viruses. Other approaches target the conserved exposed epitope of the surface exposed membrane matrix protein M2e. Well-conserved influenza proteins, such as nucleoprotein and matrix protein, are mainly targeted for developing strong cross-protective T cell responses. With multiple vaccine candidates moving along the testing and development pipeline, the field is steadily moving toward a product that is more potent, durable, and broadly protective than previously licensed vaccines. PMID:27038130

  20. Vaccine hesitancy, vaccine refusal and the anti-vaccine movement: influence, impact and implications.

    PubMed

    Dubé, Eve; Vivion, Maryline; MacDonald, Noni E

    2015-01-01

    Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of parents. Anti-vaccination movements have been implicated in lowered vaccine acceptance rates and in the increase in vaccine-preventable disease outbreaks and epidemics. In this review, we will look at determinants of parental decision-making about vaccination and provide an overview of the history of anti-vaccination movements and its clinical impact. PMID:25373435

  1. Selected anti-tumor vaccines merit a place in multimodal tumor therapies

    PubMed Central

    Weiss, Eva-Maria; Wunderlich, Roland; Ebel, Nina; Rubner, Yvonne; Schlücker, Eberhard; Meyer-Pittroff, Roland; Ott, Oliver J.; Fietkau, Rainer; Gaipl, Udo S.; Frey, Benjamin

    2012-01-01

    Multimodal approaches are nowadays successfully applied in cancer therapy. Primary locally acting therapies such as radiotherapy (RT) and surgery are combined with systemic administration of chemotherapeutics. Nevertheless, the therapy of cancer is still a big challenge in medicine. The treatments often fail to induce long-lasting anti-tumor responses. Tumor recurrences and metastases result. Immunotherapies are therefore ideal adjuncts to standard tumor therapies since they aim to activate the patient's immune system against malignant cells even outside the primary treatment areas (abscopal effects). Especially cancer vaccines may have the potential both to train the immune system against cancer cells and to generate an immunological memory, resulting in long-lasting anti-tumor effects. However, despite promising results in phase I and II studies, most of the concepts finally failed. There are some critical aspects in development and application of cancer vaccines that may decide on their efficiency. The time point and frequency of medication, usage of an adequate immune adjuvant, the vaccine's immunogenic potential, and the tumor burden of the patient are crucial. Whole tumor cell vaccines have advantages compared to peptide-based ones since a variety of tumor antigens (TAs) are present. The master requirements of cell-based, therapeutic tumor vaccines are the complete inactivation of the tumor cells and the increase of their immunogenicity. Since the latter is highly connected with the cell death modality, the inactivation procedure of the tumor cell material may significantly influence the vaccine's efficiency. We therefore also introduce high hydrostatic pressure (HHP) as an innovative inactivation technology for tumor cell-based vaccines and outline that HHP efficiently inactivates tumor cells by enhancing their immunogenicity. Finally studies are presented proving that anti-tumor immune responses can be triggered by combining RT with selected immune

  2. History of polio vaccination

    PubMed Central

    Baicus, Anda

    2012-01-01

    Poliomyelitis is an acute paralytic disease caused by three poliovirus (PV) serotypes. Less than 1% of PV infections result in acute flaccid paralysis. The disease was controlled using the formalin-inactivated Salk polio vaccine (IPV) and the Sabin oral polio vaccine (OPV). Global poliomyelitis eradication was proposed in 1988 by the World Health Organization to its member states. The strategic plan established the activities required for polio eradication, certification for regions, OPV cessation phase and post-OPV phase. OPV is the vaccine of choice for the poliomyelitis eradication program because it induces both a systemic and mucosal immune response. The major risks of OPV vaccination are the appearance of Vaccine-Associated Paralytic Poliomyelitis cases (VAPP) and the emergence of Vaccine Derived Polioviruses strains. The supplementary immunization with monovalent strains of OPV type 1 or type 3 or with a new bivalent oral polio vaccine bOPV (containing type 1 and type 3 PV) has been introduced in those regions where the virus has been difficult to control. Most countries have switched the schedule of vaccination by using IPV instead of OPV because it poses no risk of vaccine-related disease. Until 2008, poliomyelitis was controlled in Romania, an Eastern European country, predominantly using OPV. The alternative vaccination schedule (IPV/OPV) was implemented starting in September 2008, while beginning in 2009, the vaccination was IPV only. The risk of VAPP will disappear worldwide with the cessation of use of OPV. The immunization for polio must be maintained for at least 5 to 10 years using IPV. PMID:24175215

  3. [HPV prophylactic vaccines].

    PubMed

    Konopnicki, D

    2014-09-01

    Since 2007, two prophylactic vaccines against Human Papillomavirus (HPV) infection and HPV. induced lesions (both precancerous dysplasia and cancer) have been registered in Belgium. In multicentre randomized trials including more than 64,000 patients, these vaccines were shown to be highly efficient against the occurrence of condyloma and of dysplastic lesion in the cervix, vagina and vulva in females and in the anus in males. These vaccines display an excellent tolerance and safety profile, the most common adverse event being minor and transient side effects at the injection site. The protection given by these vaccines is more important in subjects that have not been in contact with HPV previously ; moreover the title of neutralizing antibodies against HPV are significantly higher in children vaccinated before 15 years-old age compared to young person vaccinated after this age. For these two reasons, it is recommended to vaccinate before the first sexual relationships. Recently, several studies have demonstrated that vaccination by two doses given at 0 and 6 months in children before 15 years-old was equivalent to the three doses scheme that should be given at 0, 1 or 2 and 6 months in subjects aged 15 years or more. In the countries that have achieved a high vaccine coverage among their young female population, the prevalence of HPV infection and the incidence of high grade cervical dysplasia have significantly decreased while condyloma has almost disappeared four years after the implementation of HPV vaccination. In HIV-positive subjects who are particularly susceptible to infection and lesions induced by HPV, vaccination brings levels of antibody comparable to what is found in the general population with similar safety. PMID:25675641

  4. Vaccination in elite athletes.

    PubMed

    Gärtner, Barbara C; Meyer, Tim

    2014-10-01

    Public health vaccination guidelines cannot be easily transferred to elite athletes. An enhanced benefit from preventing even mild diseases is obvious but stronger interference from otherwise minor side effects has to be considered as well. Thus, special vaccination guidelines for adult elite athletes are required. In most of them, protection should be strived for against tetanus, diphtheria, pertussis, influenza, hepatitis A, hepatitis B, measles, mumps and varicella. When living or traveling to endemic areas, the athletes should be immune against tick-borne encephalitis, yellow fever, Japanese encephalitis, poliomyelitis, typhoid fever, and meningococcal disease. Vaccination against pneumococci and Haemophilus influenzae type b is only relevant in athletes with certain underlying disorders. Rubella and papillomavirus vaccination might be considered after an individual risk-benefit analysis. Other vaccinations such as cholera, rabies, herpes zoster, and Bacille Calmette-Guérin (BCG) cannot be universally recommended for athletes at present. Only for a very few diseases, a determination of antibody titers is reasonable to avoid unnecessary vaccinations or to control efficacy of an individual's vaccination (especially for measles, mumps, rubella, varicella, hepatitis B and, partly, hepatitis A). Vaccinations should be scheduled in a way that possible side effects are least likely to occur in periods of competition. Typically, vaccinations are well tolerated by elite athletes, and resulting antibody titers are not different from the general population. Side effects might be reduced by an optimal selection of vaccines and an appropriate technique of administration. Very few discipline-specific considerations apply to an athlete's vaccination schedule mainly from the competition and training pattern as well as from the typical geographical distribution of competitive sites. PMID:24986118

  5. Clinical development of Ebola vaccines.

    PubMed

    Sridhar, Saranya

    2015-09-01

    The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751

  6. Clinical development of Ebola vaccines

    PubMed Central

    Sridhar, Saranya

    2015-01-01

    The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751

  7. Vaccines for lymphomas: idiotype vaccines and beyond.

    PubMed

    Houot, Roch; Levy, Ronald

    2009-05-01

    Therapeutic vaccines for lymphomas have been developed to induce active and long-lasting immune responses against lymphoma capable of eradicating the tumor. Most of these vaccines use the tumor B cell idiotype (the unique variable region of the surface immunoglobulin) as a tumor-specific antigen. The first human clinical trial for lymphoma vaccine was initiated 20 years ago. Along with several other phase I/II trials, it showed encouraging results which supported the initiation of three phase III trials. The results of these trials have recently been released (although not published yet) which failed to demonstrate a prolongation in progression-free survival following chemotherapy. Despite this disappointing result, a number of observations have accumulated over the years that suggest some clinical efficacy of lymphoma vaccines. Several strategies are being developed to improve these results that include optimization of antigen delivery and presentation as well as enhancement of anti-tumor T cell function. This review describes the clinical development of lymphoma vaccines and delineates advances, problems and prospects towards integration of this strategy in the therapeutic armamentarium for lymphoma. PMID:18951668

  8. Long-acting muscarinic antagonists for the prevention of exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Jones, Paul W

    2015-06-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) have important consequences for lung function, health status and mortality. Furthermore, they are associated with high economic costs, predominantly related to hospitalization. They are managed acutely with short-acting bronchodilators, systemic corticosteroids or antibiotics; however, a large proportion of COPD exacerbations are unreported and therefore untreated or self-managed. There is evidence to suggest that these unreported exacerbations also have important consequences for health status; therefore, reducing exacerbation risk is an important goal in the management of COPD. Current guidelines recommend long-acting muscarinic antagonists (LAMAs) as first-line bronchodilator therapy in patients with stable COPD who have a high risk of exacerbation or increased symptoms. To date, three LAMAs, tiotropium bromide, aclidinium bromide and glycopyrronium bromide, have been approved as maintenance bronchodilator treatments for stable COPD. These all provide clinically significant improvements in lung function, reduce symptoms and improve health status compared with placebo in patients with COPD. This paper reviews evidence from randomized, controlled clinical trials demonstrating that tiotropium, aclidinium and glycopyrronium reduce exacerbation risk in patients with COPD. Reductions were seen irrespective of the exacerbation measure used, whether time to first event or annualized exacerbation rate. Furthermore, studies with aclidinium suggest LAMAs can reduce exacerbation risk irrespective of whether exacerbation events are assessed, using an event-based approach or a symptom-based method which includes unreported events. Together these results demonstrate that LAMAs have the potential to provide clinical benefit in the management of exacerbations in patients with stable COPD. PMID:25801643

  9. Advances in influenza vaccination

    PubMed Central

    Reperant, Leslie A.; Rimmelzwaan, Guus F.

    2014-01-01

    Influenza virus infections yearly cause high morbidity and mortality burdens in humans, and the development of a new influenza pandemic continues to threaten mankind as a Damoclean sword. Influenza vaccines have been produced by using egg-based virus growth and passaging techniques that were developed more than 60 years ago, following the identification of influenza A virus as an etiological agent of seasonal influenza. These vaccines aimed mainly at eliciting neutralizing antibodies targeting antigenically variable regions of the hemagglutinin (HA) protein, which requires regular updates to match circulating seasonal influenza A and B virus strains. Given the relatively limited protection induced by current seasonal influenza vaccines, a more universal influenza vaccine that would protect against more—if not all—influenza viruses is among the largest unmet medical needs of the 21st century. New insights into correlates of protection from influenza and into broad B- and T-cell protective anti-influenza immune responses offer promising avenues for innovative vaccine development as well as manufacturing strategies or platforms, leading to the development of a new generation of vaccines. These aim at the rapid and massive production of influenza vaccines that provide broad protective and long-lasting immunity. Recent advances in influenza vaccine research demonstrate the feasibility of a wide range of approaches and call for the initiation of preclinical proof-of-principle studies followed by clinical trials in humans. PMID:24991424

  10. Influenza Vaccine, Live Intranasal

    MedlinePlus

    ... the next 7 days, who requires a protected environment (for example, following a bone marrow transplant). Sometimes ... The National Vaccine Injury Compensation ProgramThe National Vaccine Injury Compensation Program (VICP) is a federal program that was created to compensate people who may have ...

  11. Emerging human papillomavirus vaccines

    PubMed Central

    Ma, Barbara; Maraj, Bharat; Tran, Nam Phuong; Knoff, Jayne; Chen, Alexander; Alvarez, Ronald D; Hung, Chien-Fu; Wu, T.-C.

    2013-01-01

    Introduction Identification of human papillomavirus (HPV) as the etiologic factor of cervical, anogenital, and a subset of head and neck cancers has stimulated the development of preventive and therapeutic HPV vaccines to control HPV-associated malignancies. Excitement has been generated by the commercialization of two preventive L1-based vaccines, which use HPV virus-like particles (VLPs) to generate capsid-specific neutralizing antibodies. However, factors such as high cost and requirement for cold chain have prevented widespread implementation where they are needed most. Areas covered Next generation preventive HPV vaccine candidates have focused on cost-effective stable alternatives and generating broader protection via targeting multivalent L1 VLPs, L2 capsid protein, and chimeric L1/L2 VLPs. Therapeutic HPV vaccine candidates have focused on enhancing T cell-mediated killing of HPV-transformed tumor cells, which constitutively express HPV-encoded proteins, E6 and E7. Several therapeutic HPV vaccines are in clinical trials. Expert opinion Although progress is being made, cost remains an issue inhibiting the use of preventive HPV vaccines in countries that carry the majority of the cervical cancer burden. In addition, progression of therapeutic HPV vaccines through clinical trials may require combination strategies employing different therapeutic modalities. As research in the development of HPV vaccines continues, we may generate effective strategies to control HPV-associated malignancies. PMID:23163511

  12. Vaccination to Prevent Cancer.

    PubMed

    Clements, Dennis

    2016-01-01

    Vaccines stimulate the immune system, mimicking infectious attacks and thereby promoting the development of protective antibodies and/or cellular immunity so that the body is immune to infection when live native infections attack. Some of these infections are associated with cancer-causing changes in the body; thus some vaccines may help prevent cancer. PMID:27621345

  13. Influenza vaccination during pregnancy.

    PubMed

    2016-02-01

    In a randomised, double-blind trial in pregnant women, a seasonal inactivated influenza vaccine without a lipid adjuvant and covering strain A/H1N1v was partially effective: the incidence of influenza in the mothers and their infants was about 1.8% with the vaccine versus 3.6% with placebo. No noteworthy adverse reactions were reported. PMID:27042735

  14. Pricing of new vaccines

    PubMed Central

    McGlone, Sarah M

    2010-01-01

    New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following eleven components: (1) Conduct a target population analysis; (2) Map potential competitors and alternatives; (3) Construct a vaccine target product profile (TPP) and compare it to projected or actual TPPs of competing vaccines; (4) Quantify the incremental value of the new vaccine's characteristics; (5) Determine vaccine positioning in the marketplace; (6) Estimate the vaccine price-demand curve; (7) Calculate vaccine costs (including those of manufacturing, distribution, and research and development); (8) Account for various legal, regulatory, third party payer and competitor factors; (9) Consider the overall product portfolio; (10) Set pricing objectives; (11) Select pricing and pricing structure. While the biomedical literature contains some studies that have addressed these components, there is still considerable room for more extensive evaluation of this important area. PMID:20861678

  15. Chimeric Pestivirus Experimental Vaccines.

    PubMed

    Reimann, Ilona; Blome, Sandra; Beer, Martin

    2016-01-01

    Chimeric pestiviruses have shown great potential as marker vaccine candidates against pestiviral infections. Exemplarily, we describe here the construction and testing of the most promising classical swine fever vaccine candidate "CP7_E2alf" in detail. The description is focused on classical cloning technologies in combination with reverse genetics. PMID:26458840

  16. The Human Hookworm Vaccine.

    PubMed

    Hotez, Peter J; Diemert, David; Bacon, Kristina M; Beaumier, Coreen; Bethony, Jeffrey M; Bottazzi, Maria Elena; Brooker, Simon; Couto, Artur Roberto; Freire, Marcos da Silva; Homma, Akira; Lee, Bruce Y; Loukas, Alex; Loblack, Marva; Morel, Carlos Medicis; Oliveira, Rodrigo Correa; Russell, Philip K

    2013-04-18

    Hookworm infection is one of the world's most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries. A Human Hookworm Vaccine is currently being developed by the Sabin Vaccine Institute and is in phase 1 clinical testing. The candidate vaccine is comprised of two recombinant antigens known as Na-GST-1 and Na-APR-1, each of which is an important parasite enzyme required for hookworms to successfully utilize host blood as a source of energy. The recombinant proteins are formulated on Alhydrogel(®) and are being tested in combination with a synthetic Toll-like receptor 4 agonist. The aim of the vaccine is to induce anti-enzyme antibodies that will reduce both host blood loss and the number of hookworms attached to the gut. Transfer of the manufacturing technology to the Oswaldo Cruz Foundation (FIOCRUZ)/Bio-Manguinhos (a Brazilian public sector developing country vaccine manufacturer) is planned, with a clinical development plan that could lead to registration of the vaccine in Brazil. The vaccine would also need to be introduced in the poorest regions of Africa and Asia, where hookworm infection is highly endemic. Ultimately, the vaccine could become an essential tool for achieving hookworm control and elimination, a key target in the 2012 London Declaration on Neglected Tropical Diseases. PMID:23598487

  17. Influenza: the virus and prophylaxis with inactivated influenza vaccine in "at risk" groups, including COPD patients.

    PubMed

    Hovden, Arnt-Ove; Cox, Rebecca Jane; Haaheim, Lars Reinhardt

    2007-01-01

    Influenza is a major respiratory pathogen, which exerts a huge human and economic toll on society. Influenza is a vaccine preventable disease, however, the vaccine strains must be annually updated due to the continuous antigenic changes in the virus. Inactivated influenza vaccines have been used for over 50 years and have an excellent safety record. Annual vaccination is therefore recommended for all individuals with serious medical conditions, like COPD, and protects the vaccinee against influenza illness and also against hospitalization and death. In COPD patients, influenza infection can lead to exacerbations resulting in reduced quality of life, hospitalization and death in the most severe cases. Although there is only limited literature on the use of influenza vaccination solely in COPD patients, there is clearly enough evidence to recommend annual vaccination in this group. This review will focus on influenza virus and prophylaxis with inactivated influenza vaccines in COPD patients and other "at risk" groups to reduce morbidity, save lives, and reduce health care costs. PMID:18229561

  18. Vaccine-preventable diseases in humanitarian emergencies among refugee and internally-displaced populations.

    PubMed

    Lam, Eugene; McCarthy, Amanda; Brennan, Muireann

    2015-01-01

    Humanitarian emergencies may result in breakdown of regular health services including routine vaccination programs. Displaced populations including refugees and internally displaced persons are particularly susceptible to outbreaks of communicable diseases such as vaccine-preventable diseases (VPDs). Common VPDs encountered in humanitarian emergencies include measles, polio, and depending on geographical location, meningococcal meningitis, yellow fever, hepatitis A, and cholera. We conducted a review of 50 published articles from 2000 to 2015 concerning VPDs in humanitarian emergencies. This article provides an update on the available literature regarding vaccinations among this highly vulnerable population and describes the unique challenges of VPDs during humanitarian emergencies. Humanitarian emergencies place affected populations at risk for elevated morbidity and mortality from VPDs due to creation or exacerbation of factors associated with disease transmission such as mass population movements, overcrowding, malnutrition, and poor water and sanitation conditions. Vaccination is one of the most basic and critical health interventions for protecting vulnerable populations during emergencies. Growing insecurity, as seen in the increasing number of targeted attacks on health workers in recent years, as well as destruction of cold chain and infrastructure for transportation of supplies, are creating new challenges in provision of life saving vaccines in conflict settings. Population displacement can also threaten global VPD eradication and elimination efforts. While highly effective vaccines and guidelines to combat VPDs are available, the trend of increasing number of humanitarian emergencies globally poses new and emerging challenges in providing vaccination among displaced populations. PMID:26406333

  19. [Experimental, clinical and immunologic assessment of acellular staphylococcal vaccine "Staphylovac"].

    PubMed

    Egorova, N B; Efremova, V N; Kurbatova, E A; Gruber, I M

    2008-01-01

    Results of experimental, clinical and immunological effects of acellular dry staphylococcal vaccine "Staphylovac" developed in Mechnikov Research Institute of Vaccines and Sera are presented. Original mildly virulent strains of Staphylococcus aureus having high immunogenicity, and intra- and interspecies protective activity against different representatives of opportunistic microflora were used for construction of the preparation. Low-toxicity and weak anapylactogenicity of the vaccine were established. In experiments on mice, guinea pigs and rabbits significant protective, antigenic and immunomodulate activity of the preparation was revealed with low sensitization of animals. Clinical trials performed in different centers showed that inclusion of vaccinotherapy in complex treatment of chronic staphylococcal infections (chronic pyodermia, lung abscess etc.) resulted in prolonged pathologic locus, decrease of number and severity of exacerbations, prolongation of remission, and complete recovery in significant number of patients. Activation of innate and adaptive immunity was revealed in the same patients. It was shown on the large group of athletes that administration of the vaccine by aerosol route prevents disruption of immunologic adaptation occurring due to excess physical activity and stress situations during competitions. PMID:19186558

  20. Vaccines for military use.

    PubMed

    Artenstein, Andrew W

    2009-11-01

    Vaccines have long been used by military forces in order to prevent communicable diseases and thereby preserve the fighting force. A tradition that began with the mass vaccination of the Continental Army against smallpox during the War of the American Revolution in the late 18th century continues today with routine and deployment-based vaccination of military forces against potential pathogens of nature and biological weapon threats. As their role has expanded in recent years to include humanitarian and peacekeeping missions, the military's use of vaccines against infectious diseases has concomitantly broadened to include civilian populations worldwide. The emergence of new threats and the recognition of additional global challenges will continue to compel the development and promotion of vaccines to combat infectious diseases of military significance. PMID:19837279

  1. Diagnostic and vaccine chapter.

    PubMed

    Wolfram, J H; Kokanov, S K; Verkhovsky, O A

    2010-10-01

    The first report in this chapter describes the development of a killed composite vaccine. This killed vaccine is non-infectious to humans, other animals, and the environment. The vaccine has low reactivity, is non-abortive, and does not induce pathomorphological alterations to the organs of vaccinated animals. The second report of this chapter describes the diagnostic value of a competitive enzyme-linked immunosorbent assay for detecting Brucella-specific antibodies and its ability to discriminate vaccinated cattle from infected cattle. The results indicated that the competitive enzyme-linked immunosorbent assay is more sensitive than traditional tests for detecting antibodies to Brucella abortus in naturally and experimentally infected cattle. PMID:20850688

  2. Against vaccine assay secrecy

    PubMed Central

    Herder, Matthew; Hatchette, Todd F; Halperin, Scott A; Langley, Joanne M

    2015-01-01

    Increasing the transparency of the evidence base behind health interventions such as pharmaceuticals, biologics, and medical devices, has become a major point of critique, conflict, and policy focus in recent years. Yet the lack of publicly available information regarding the immunogenicity assays upon which many important, widely used vaccines are based has received no attention to date. In this paper we draw attention to this critical public health problem by reporting on our efforts to secure vaccine assay information in respect of 10 vaccines through Canada's access to information law. We argue, under Canadian law, that the public health interest in having access to the methods for these laboratory procedures should override claims by vaccine manufacturers and regulators that this information is proprietary; and, we call upon several actors to take steps to ensure greater transparency with respect to vaccine assays, including regulators, private firms, researchers, research institutions, research funders, and journal editors. PMID:25826194

  3. 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. PMID:22002157

  4. Developing new smallpox vaccines.

    PubMed Central

    Rosenthal, S. R.; Merchlinsky, M.; Kleppinger, C.; Goldenthal, K. L.

    2001-01-01

    New stockpiles of smallpox vaccine are required as a contingency for protecting civilian and military personnel against deliberate dissemination of smallpox virus by terrorists or unfriendly governments. The smallpox vaccine in the current stockpile consists of a live animal poxvirus (Vaccinia virus [VACV]) that was grown on the skin of calves. Because of potential issues with controlling this earlier manufacturing process, which included scraping VACV lesions from calfskin, new vaccines are being developed and manufactured by using viral propagation on well-characterized cell substrates. We describe, from a regulatory perspective, the various strains of VACV, the adverse events associated with calf lymph-propagated smallpox vaccine, the issues regarding selection and use of cell substrates for vaccine production, and the issues involved in demonstrating evidence of safety and efficacy. PMID:11747717

  5. [Varicella vaccination: who should be vaccinated these days?].

    PubMed

    Hügle, Boris; Suchowerskyj, Philipp; Schuster, Volker

    2005-02-24

    In July 2004 the STIKO (German National Commission for Vaccinations) recommended routine varicella vaccination (together with the first MMR vaccination) for all healthy infants. The previous recommendations for vaccination of adolescents with no history of varicella and patient groups at risk remain valid. In persons with severely depressed cellular immunity or pregnant women vaccination with live attenuated VZV vaccines is contraindicated. Experience gained in the United States show that widespread introduction of VZV vaccination results in a decrease in both the incidence of varicella and concomitant complications including herpes zoster. PMID:18441563

  6. Vaccination coverage among adults, excluding influenza vaccination - United States, 2013.

    PubMed

    Williams, Walter W; Lu, Peng-Jun; O'Halloran, Alissa; Bridges, Carolyn B; Kim, David K; Pilishvili, Tamara; Hales, Craig M; Markowitz, Lauri E

    2015-02-01

    Vaccinations are recommended throughout life to prevent vaccine-preventable diseases and their sequelae. Adult vaccination coverage, however, remains low for most routinely recommended vaccines and below Healthy People 2020 targets. In October 2014, the Advisory Committee on Immunization Practices (ACIP) approved the adult immunization schedule for 2015. With the exception of influenza vaccination, which is recommended for all adults each year, other adult vaccinations are recommended for specific populations based on a person's age, health conditions, behavioral risk factors (e.g., injection drug use), occupation, travel, and other indications. To assess vaccination coverage among adults aged ≥19 years for selected vaccines, CDC analyzed data from the 2013 National Health Interview Survey (NHIS). This report highlights results of that analysis for pneumococcal, tetanus toxoid-containing (tetanus and diphtheria vaccine [Td] or tetanus and diphtheria with acellular pertussis vaccine [Tdap]), hepatitis A, hepatitis B, herpes zoster (shingles), and human papillomavirus (HPV) vaccines by selected characteristics (age, race/ethnicity,† and vaccination indication). Influenza vaccination coverage estimates for the 2013-14 influenza season have been published separately. Compared with 2012, only modest increases occurred in Tdap vaccination among adults aged ≥19 years (a 2.9 percentage point increase to 17.2%), herpes zoster vaccination among adults aged ≥60 years (a 4.1 percentage point increase to 24.2%), and HPV vaccination among males aged 19-26 years (a 3.6 percentage point increase to 5.9%); coverage among adults in the United States for the other vaccines did not improve. Racial/ethnic disparities in coverage persisted for all six vaccines and widened for Tdap and herpes zoster vaccination. Increases in vaccination coverage are needed to reduce the occurrence of vaccine-preventable diseases among adults. Awareness of the need for vaccines for adults is low

  7. Quantitative measurement of epidermal growth factor receptor-mitogen-activated protein kinase signal transduction using a nine-plex, peptide-based immunoassay.

    PubMed

    Rauh-Adelmann, Christine; Moskow, John M; Graham, James R; Yen, Lucy G; Boucher, Jeffrey I; Murphy, Cheryl E; Nadler, Timothy K; Gordon, Neal F; Radding, Jeffrey A

    2008-04-15

    Aberrant epidermal growth factor receptor (EGFR, ErbB1) signaling is implicated in cell transformation, motility, and invasion in a variety of cell types, and EGFR is the target of several anticancer drugs. However, the kinetics of EGFR signaling and the individual contributions of site-specific phosphorylation events remain largely unknown. A peptide-based, multiplex immunoassay approach was developed to simultaneously measure both total and phosphorylated protein in a single sample. The approach involves the proteolytic digestion of proteins prior to the isolation and quantitation of site-specific phosphorylation events within an individual protein. Quantitation of phosphorylated and total proteins, in picomolar to nanomolar concentrations, were interpolated from standard curves generated with synthetic peptides that correspond to the peptide targets used in the immunoassays. In this study, a bead-based, nine-plex immunoassay measuring total and phosphorylated protein was constructed to measure temporal, site-specific phosphorylation of key members of the EGFR pathway (ErbB1 receptor, MEK1, MEK2, ERK1, and ERK2) in A431 cells stimulated with epidermal growth factor. The effect of MEK inhibition on this pathway was determined using a known MEK kinase inhibitor, SL327. The results reported herein are the first quantitative measurements of site-specific phosphorylation events and total proteins in a single sample, at the same time representing a new paradigm for standardized protein and phosphorylation analysis using multiplexed, peptide-based, sandwich immunoassays. PMID:18275835

  8. Vaccines for Canine Leishmaniasis

    PubMed Central

    Palatnik-de-Sousa, Clarisa B.

    2012-01-01

    Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL) is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global warming, coinfection with immunosuppressive diseases, and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL) in the Americas, the Middle East, Central Asia, China, and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases, and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost–effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine VL. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans and dogs against VL. PMID:22566950

  9. Laser vaccine adjuvants

    PubMed Central

    Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

    2014-01-01

    Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines. PMID:25424797

  10. Vaccines against nicotine.

    PubMed

    Cerny, Erich H; Cerny, Thomas

    2009-04-01

    Medications against any dependence-inducing drug face a dilemma: if they are efficient, they will induce withdrawal symptoms and the patient is likely to stop taking his medication. Anti drug vaccines are irreversible, provide protection over years and need booster injections far beyond the critical phase of acute withdrawal symptoms. Interacting rather with the drug in the blood than with a receptor in the brain, the vaccines are, in addition, free of side effects due to central interaction. For drugs like nicotine interacting with different types of receptors in many organs, this is a further advantage. There are three reasons that anti drug vaccines have first been developed against nicotine. Firstly, in most parts of the world 20 to 50% of the adult population smoke and any smoking cessation treatment will have an important impact on public health and be commercially a very attractive product. The second reason are the smokers themselves, who would like to quit in significant numbers and who have shown good compliance for any form of treatment. Thirdly, the quantities of cocaine or heroine taken by dependant persons are higher than the quantity of nicotine per cigarette, which makes an anti nicotine vaccine the easier vaccine project. Three anti nicotine vaccines are today in an advanced stage of clinical evaluation. We report here how those vaccines work, on the progress of the trials and future developments to expect. Results show that the efficiency of the vaccines is directly related to the antibody levels of the probates, a fact which will help to optimize further the vaccine effect. We expect the vaccines to appear on the market during a time window between 2009 and 2011. PMID:19276649

  11. Lassa fever vaccine.

    PubMed

    Fisher-Hoch, Susan P; McCormick, Joseph B

    2004-04-01

    Lassa fever remains a serious challenge to public health in West Africa threatening both local residents in rural areas and those who serve them, particularly medical care providers. Given the ecology of the rodent host and conditions in the endemic area, a vaccine is mandatory for control. The challenge is to overcome the scientific, political and economic obstacles to producing a human use vaccine candidate. There are some scientific issues to resolve. It is known that the G-protein confers protection but we do not know its duration. If the N-protein is also included there may be a better duration of protection but it is unclear whether the N-protein as a vaccine may possibly enhance the infection. The original vaccinia vector must be replaced by new vectors, chimeras or by delivering DNA in some format. A live vaccine is attractive because it can confer protection in a single shot. A killed vaccine is more stable, particularly for distribution in the tropics but usually requires repeated shots. For practical reasons a live vaccine format should probably be pursued, which could then be combined with a yellow fever vaccine, using the same cold chains, since this disease occupies the same endemic areas in West Africa. Lassa vaccine initiatives have suffered from a lack of funding in the past but bioterrorism has brought new resources to Lassa virus science. Adequate funding and applications of new vaccine technologies give hope that we may soon see a vaccine in clinical trials. However, the difficulty of conducting trials in endemic areas and lack of political stability remain serious problems. PMID:15056044

  12. The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety.

    PubMed

    McNeil, Michael M; Gee, Julianne; Weintraub, Eric S; Belongia, Edward A; Lee, Grace M; Glanz, Jason M; Nordin, James D; Klein, Nicola P; Baxter, Roger; Naleway, Allison L; Jackson, Lisa A; Omer, Saad B; Jacobsen, Steven J; DeStefano, Frank

    2014-09-22

    The Vaccine Safety Datalink (VSD) is a collaborative project between the Centers for Disease Control and Prevention (CDC) and 9 health care organizations. Established in 1990, VSD is a vital resource informing policy makers and the public about the safety of vaccines used in the United States. Large linked databases are used to identify and evaluate adverse events in over 9 million individuals annually. VSD generates rapid, important safety assessments for both routine vaccinations and emergency vaccination campaigns. VSD monitors safety of seasonal influenza vaccines in near-real time, and provided essential information on the safety of influenza A (H1N1) 2009 monovalent vaccine during the recent pandemic. VSD investigators have published important studies demonstrating that childhood vaccines are not associated with autism or other developmental disabilities. VSD prioritizes evaluation of new vaccines; searches for possible unusual health events after vaccination; monitors vaccine safety in pregnant women; and has pioneered development of biostatistical research methods. PMID:25108215

  13. Entirely Carbohydrate-Based Vaccines: An Emerging Field for Specific and Selective Immune Responses.

    PubMed

    Nishat, Sharmeen; Andreana, Peter R

    2016-01-01

    Carbohydrates are regarded as promising targets for vaccine development against infectious disease because cell surface glycans on many infectious agents are attributed to playing an important role in pathogenesis. In addition, oncogenic transformation of normal cells, in many cases, is associated with aberrant glycosylation of the cell surface glycan generating tumor associated carbohydrate antigens (TACAs). Technological advances in glycobiology have added a new dimension to immunotherapy when considering carbohydrates as key targets in developing safe and effective vaccines to combat cancer, bacterial infections, viral infections, etc. Many consider effective vaccines induce T-cell dependent immunity with satisfactory levels of immunological memory that preclude recurrence. Unfortunately, carbohydrates alone are poorly immunogenic as they do not bind strongly to the MHCII complex and thus fail to elicit T-cell immunity. To increase immunogenicity, carbohydrates have been conjugated to carrier proteins, which sometimes can impede carbohydrate specific immunity as peptide-based immune responses can negate antibodies directed at the targeted carbohydrate antigens. To overcome many challenges in using carbohydrate-based vaccine design and development approaches targeting cancer and other diseases, zwitterionic polysaccharides (ZPSs), isolated from the capsule of commensal anaerobic bacteria, will be discussed as promising carriers of carbohydrate antigens to achieve desired immunological responses. PMID:27213458

  14. Entirely Carbohydrate-Based Vaccines: An Emerging Field for Specific and Selective Immune Responses

    PubMed Central

    Nishat, Sharmeen; Andreana, Peter R.

    2016-01-01

    Carbohydrates are regarded as promising targets for vaccine development against infectious disease because cell surface glycans on many infectious agents are attributed to playing an important role in pathogenesis. In addition, oncogenic transformation of normal cells, in many cases, is associated with aberrant glycosylation of the cell surface glycan generating tumor associated carbohydrate antigens (TACAs). Technological advances in glycobiology have added a new dimension to immunotherapy when considering carbohydrates as key targets in developing safe and effective vaccines to combat cancer, bacterial infections, viral infections, etc. Many consider effective vaccines induce T-cell dependent immunity with satisfactory levels of immunological memory that preclude recurrence. Unfortunately, carbohydrates alone are poorly immunogenic as they do not bind strongly to the MHCII complex and thus fail to elicit T-cell immunity. To increase immunogenicity, carbohydrates have been conjugated to carrier proteins, which sometimes can impede carbohydrate specific immunity as peptide-based immune responses can negate antibodies directed at the targeted carbohydrate antigens. To overcome many challenges in using carbohydrate-based vaccine design and development approaches targeting cancer and other diseases, zwitterionic polysaccharides (ZPSs), isolated from the capsule of commensal anaerobic bacteria, will be discussed as promising carriers of carbohydrate antigens to achieve desired immunological responses. PMID:27213458

  15. Towards a vaccine for chronic obstructive pulmonary disease.

    PubMed

    Clancy, R L

    2012-06-01

    This review discusses chronic obstructive pulmonary disease as an outcome of two pathogenic pathways: the first resulting from inhalation of toxins and the second a consequence of bacterial colonisation of damaged airways. Earlier assessment of the role played by bacteria in acute exacerbations was compromised by a deficiency of quality data and the use of parameters more relevant to invasive infection. Data are reviewed to support a hypothesis that states intrabronchial inflammation reflects an excessive and inappropriate host response (largely mediated by Th17 cells derived from gut-associated lymphoid tissues) to colonising bacteria acting as an 'antigen sump' (in essence, a hypersensitivity reaction). It is proposed that both viral and bacterial infections exacerbate inflammation through a common pathway that involves colonising bacteria. An oral vaccine containing inactivated non-typeable Haemophilus influenzae augments a protective loop that involves the aspiration of bronchus content into the gut and reduces the severity of acute exacerbations including the need for hospital admission by reducing the 'load' of bacteria comprising this final common path. The positive clinical results from trials using oral NTHi support both the concept that bacterial colonisation of damaged airways is a potent second pathogenic pathway and that oral immunotherapy provides a significant therapeutic advance in limiting damage in chronic obstructive pulmonary disease. PMID:22372964

  16. Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease.

    PubMed

    Wedzicha, Jadwiga A; Brill, Simon E; Allinson, James P; Donaldson, Gavin C

    2013-01-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients. Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the 'frequent exacerbator' phenotype. This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes. These patients are therefore a priority for research and treatment. The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection. Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment. Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype. This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities. PMID:23945277

  17. The role of viral infections in exacerbations of chronic obstructive pulmonary disease and asthma.

    PubMed

    Hewitt, Richard; Farne, Hugo; Ritchie, Andrew; Luke, Emma; Johnston, Sebastian L; Mallia, Patrick

    2016-04-01

    Asthma and chronic obstructive pulmonary disease (COPD) are major causes of global morbidity and mortality worldwide. The clinical course of both asthma and COPD are punctuated by the occurrence of exacerbations, acute events characterized by increased symptoms and airflow obstruction. Exacerbations contribute most of the morbidity, mortality and excess healthcare costs associated with both asthma and COPD. COPD and asthma exacerbations are frequently associated with respiratory virus infections and this has led to an intense research focus into the mechanisms of virus-induced exacerbations over the past decade. Current therapies are effective in reducing chronic symptoms but are less effective in preventing exacerbations, particularly in COPD. Understanding the mechanisms of virus-induced exacerbation will lead to the development of new targeted therapies that can reduce the burden of virus-induced exacerbations. In this review we discuss current knowledge of virus-induced exacerbations of asthma and COPD with a particular focus on mechanisms, human studies, virus-bacteria interactions and therapeutic advances. PMID:26611907

  18. Immunopathology of RSV infection: prospects for developing vaccines without this complication.

    PubMed

    van Drunen Littel-van den Hurk, S; Mapletoft, J W; Arsic, N; Kovacs-Nolan, J

    2007-01-01

    Respiratory syncytial virus is the most important cause of lower respiratory tract infection in infants and young children. RSV clinical disease varies from rhinitis and otitis media to bronchiolitis and pneumonia. An increased incidence of asthma later in life has been associated with the more severe lower respiratory tract infections. Despite its importance as a pathogen, there is no licensed vaccine against RSV. This is due to a number of factors complicating the development of an effective and safe vaccine. The immunity to natural RSV infection is incomplete as re-infections occur in all age groups, which makes it challenging to design a protective vaccine. Second, the primary target population is the newborn infant, which has a relatively immature immune system and maternal antibodies that can interfere with vaccination. Finally, some vaccines have resulted in a predisposition for exacerbated pulmonary disease in infants, which was attributed to an imbalanced Th2-biased immune response, although the exact cause has not been elucidated. This makes it difficult to proceed with vaccine testing in infants. It is likely that an effective and safe vaccine needs to elicit a balanced immune response, including RSV-specific neutralising antibodies, CD8 T-cells, Th1/Th2 CD4 T-cells and preferably secretory IgA. Subunit vaccines formulated with appropriate adjuvants may be adequate for previously exposed individuals. However, intranasally delivered genetically engineered attenuated or vectored vaccines are currently most promising for newborns, as they are expected to induce a balanced immune response similar to that elicited to natural infection and not be subject to interference from maternal antibodies. Maternal vaccination may be the optimal strategy to protect the very young infants. PMID:17004293

  19. Bioinformatics analysis of Brucella vaccines and vaccine targets using VIOLIN

    PubMed Central

    2010-01-01

    Background Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis, one of the commonest zoonotic diseases found worldwide in humans and a variety of animal species. While several animal vaccines are available, there is no effective and safe vaccine for prevention of brucellosis in humans. VIOLIN (http://www.violinet.org) is a web-based vaccine database and analysis system that curates, stores, and analyzes published data of commercialized vaccines, and vaccines in clinical trials or in research. VIOLIN contains information for 454 vaccines or vaccine candidates for 73 pathogens. VIOLIN also contains many bioinformatics tools for vaccine data analysis, data integration, and vaccine target prediction. To demonstrate the applicability of VIOLIN for vaccine research, VIOLIN was used for bioinformatics analysis of existing Brucella vaccines and prediction of new Brucella vaccine targets. Results VIOLIN contains many literature mining programs (e.g., Vaxmesh) that provide in-depth analysis of Brucella vaccine literature. As a result of manual literature curation, VIOLIN contains information for 38 Brucella vaccines or vaccine candidates, 14 protective Brucella antigens, and 68 host response studies to Brucella vaccines from 97 peer-reviewed articles. These Brucella vaccines are classified in the Vaccine Ontology (VO) system and used for different ontological applications. The web-based VIOLIN vaccine target prediction program Vaxign was used to predict new Brucella vaccine targets. Vaxign identified 14 outer membrane proteins that are conserved in six virulent strains from B. abortus, B. melitensis, and B. suis that are pathogenic in humans. Of the 14 membrane proteins, two proteins (Omp2b and Omp31-1) are not present in B. ovis, a Brucella species that is not pathogenic in humans. Brucella vaccine data stored in VIOLIN were compared and analyzed using the VIOLIN query system. Conclusions Bioinformatics curation and ontological

  20. [Current events in vaccination].

    PubMed

    Aubert, M; Aumaître, H; Beytout, J; Bloch, K; Bouhour, D; Callamand, P; Chave, C; Cheymol, J; Combadière, B; Dahlab, A; Denis, F; De Pontual, L; Dodet, B; Dommergues, M-A; Dufour, V; Gagneur, A; Gaillat, J; Gaudelus, J; Gavazzi, G; Gillet, Y; Gras-le-Guen, C; Haas, H; Hanslik, T; Hau-Rainsard, I; Larnaudie, S; Launay, O; Lorrot, M; Loulergue, P; Malvy, D; Marchand, S; Picherot, G; Pinquier, D; Pulcini, C; Rabaud, C; Regnier, F; Reinert, P; Sana, C; Savagner, C; Soubeyrand, B; Stephan, J-L; Strady, C

    2011-11-01

    The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve - but for how long ? - the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine

  1. [Current events in vaccination].

    PubMed

    Aubert, M; Aumaître, H; Beytout, J; Bloch, K; Bouhour, D; Callamand, P; Chave, C; Cheymol, J; Combadière, B; Dahlab, A; Denis, F; De Pontual, L; Dodet, B; Dommergues, M A; Dufour, V; Gagneur, A; Gaillat, J; Gaudelus, J; Gavazzi, G; Gillet, Y; Gras-le-Guen, C; Haas, H; Hanslik, T; Hau-Rainsard, I; Larnaudie, S; Launay, O; Lorrot, M; Loulergue, P; Malvy, D; Marchand, S; Picherot, G; Pinquier, D; Pulcini, C; Rabaud, C; Regnier, F; Reinert, P; Sana, C; Savagner, C; Soubeyrand, B; Stephan, J L; Strady, C

    2011-05-01

    The annual meeting of the Infectious Disease Society of America (IDSA); which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve--but for how long?--the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55%, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine

  2. Decreased expression of ectonucleotidase E-NPP1 in leukocytes from subjects with severe asthma exacerbation.

    PubMed

    Montaño, L M; Vargas, M H; Díaz-Hernández, V; De Ita, M; Kazakova, R; Barajas-López, C

    2016-01-01

    Several studies suggest that ATP and related nucleotides play a role in the pathophysiology of asthma. However, the functionality of ectonucleotidases in this disease has been scantly investigated. We studied total ectonucleotidase activity in leukocytes from patients suffering from asthma exacerbation and explored the expression of E-NTPDase 1, 2, 3, and 8, and E-NPP1, 2, and 3, in their polymorphonuclear cells by immunofluorescence and qPCR. Leukocytes from patients with mild or moderate asthma exacerbation had similar ectonucleotidase activity than leukocytes from healthy subjects, while in patients with severe asthma exacerbation, this activity was lower. Of the ectonucleotidases studied, only E-NPP1 displayed diminished immunofluorescence and a significant decrease in its mRNA expression, both in patients with severe asthma exacerbation. This reduced E-NPP1 expression could be responsible for increased amounts of ATP or other nucleotides, capable of worsening asthma exacerbation, and warranting further investigation. PMID:26405014

  3. Exacerbations of asthma during pregnancy: Impact on pregnancy complications and outcome.

    PubMed

    Ali, Z; Hansen, A V; Ulrik, C S

    2016-05-01

    Asthma is common among pregnant women, and the incidence of asthma exacerbations during pregnancy is high. This literature review provides an overview of the impact of exacerbations of asthma during pregnancy on pregnancy-related complications. The majority of published retrospective studies reveal that asthma exacerbations during pregnancy increase the risk of pre-eclampsia, gestational diabetes, placental abruption and placenta praevia. Furthermore, these women also have higher risk for breech presentation, haemorrhage, pulmonary embolism, caesarean delivery, maternal admission to the intensive care unit and longer postpartum hospital stay. Asthma has been associated with increased risk of intrauterine growth retardation, small-for-gestational age, low birth weight, infant hypoglycaemia and preterm birth, but more recent prospective studies have not revealed significant associations with regard to these outcomes. In conclusion, asthma exacerbations during pregnancy are associated with complications of pregnancy, labour and delivery. Prevention of exacerbations is essential to reduce the risk of complications and poor outcome. PMID:26467747

  4. Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2): study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. Methods This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data

  5. Vaccinations for the Older Adult.

    PubMed

    Gnanasekaran, Gowrishankar; Biedenbender, Rex; Davidson, Harley Edward; Gravenstein, Stefan

    2016-08-01

    Vaccine response declines with age, but currently recommended vaccines are safe and effective in reducing, if not preventing, disease altogether. Over the last decade, advancements in vaccine immunogenicity, either by increasing dose or conjugating vaccines to protein, have resulted in more immunogenic vaccines that also seem more effective in reducing clinical disease both for influenza and pneumococcus. Meanwhile, there is a resurgence in incident pertussis, exceeding prevalence from five decades ago, adding older adults to a recommended target vaccination group. This article discusses currently available vaccines, in the context of current epidemiology and recommendations, for older adults. PMID:27394026

  6. Tuberculosis vaccines in clinical trials

    PubMed Central

    Rowland, Rosalind; McShane, Helen

    2011-01-01

    Effective prophylactic and/or therapeutic vaccination is a key strategy for controlling the global TB epidemic. The partial effectiveness of the existing TB vaccine, bacille Calmette–Guérin (BCG), suggests effective vaccination is possible and highlights the need for an improved vaccination strategy. Clinical trials are evaluating both modifications to the existing BCG immunization methods and also novel TB vaccines, designed to replace or boost BCG. Candidate vaccines in clinical development include live mycobacterial vaccines designed to replace BCG, subunit vaccines designed to boost BCG and therapeutic vaccines designed as an adjunct to chemotherapy. There is a great need for validated animal models, identification of immunological biomarkers of protection and field sites with the capacity for large-scale efficacy testing in order to develop and license a novel TB vaccine or regimen. PMID:21604985

  7. Novel Vaccination Strategies against Tuberculosis

    PubMed Central

    Andersen, Peter; Kaufmann, Stefan H.E.

    2014-01-01

    The tuberculosis (TB) pandemic continues to rampage despite widespread use of the BCG (Bacillus Calmette–Guérin) vaccine. Novel vaccination strategies are urgently needed to arrest global transmission and prevent the uncontrolled development of multidrug-resistant forms of Mycobacterium tuberculosis. Over the last two decades, considerable progress has been made in the field of vaccine development with numerous innovative preclinical candidates and more than a dozen vaccines in clinical trials. These vaccines are developed either as boosters of the current BCG vaccine or as novel prime vaccines to replace BCG. Given the enormous prevalence of latent TB infection, vaccines that are protective on top of an already established infection remain a high priority and a significant scientific challenge. Here we discuss the current state of TB vaccine research and development, our understanding of the underlying immunology, and the requirements for an efficient TB vaccine. PMID:24890836

  8. A score to predict short-term risk of COPD exacerbations (SCOPEX)

    PubMed Central

    Make, Barry J; Eriksson, Göran; Calverley, Peter M; Jenkins, Christine R; Postma, Dirkje S; Peterson, Stefan; Östlund, Ollie; Anzueto, Antonio

    2015-01-01

    Background There is no clinically useful score to predict chronic obstructive pulmonary disease (COPD) exacerbations. We aimed to derive this by analyzing data from three existing COPD clinical trials of budesonide/formoterol, formoterol, or placebo in patients with moderate-to-very-severe COPD and a history of exacerbations in the previous year. Methods Predictive variables were selected using Cox regression for time to first severe COPD exacerbation. We determined absolute risk estimates for an exacerbation by identifying variables in a binomial model, adjusting for observation time, study, and treatment. The model was further reduced to clinically useful variables and the final regression coefficients scaled to obtain risk scores of 0–100 to predict an exacerbation within 6 months. Receiver operating characteristic (ROC) curves and the corresponding C-index were used to investigate the discriminatory properties of predictive variables. Results The best predictors of an exacerbation in the next 6 months were more COPD maintenance medications prior to the trial, higher mean daily reliever use, more exacerbations during the previous year, lower forced expiratory volume in 1 second/forced vital capacity ratio, and female sex. Using these risk variables, we developed a score to predict short-term (6-month) risk of COPD exacerbations (SCOPEX). Budesonide/formoterol reduced future exacerbation risk more than formoterol or as-needed short-acting β2-agonist (salbutamol). Conclusion SCOPEX incorporates easily identifiable patient characteristics and can be readily applied in clinical practice to target therapy to reduce COPD exacerbations in patients at the highest risk. PMID:25670896

  9. [Vaccines for the future].

    PubMed

    Girard, M P

    2009-05-01

    The field of vaccines and vaccinology has seen remarkable progress during the past 20 years. Many vaccines, however, still need to be improved, either because the protection they provide is relatively short-lived and would greatly benefit from the development of booster formulations (as is the case for tuberculosis), or because they only cover part of the many serotypes of the pathogen that causes the disease (rotaviruses, papillomaviruses, or Streptococcus pneumoniae). In addition, still many diseases lack a proper preventive vaccine, such as AIDS, hepatitis C, malaria, viral pneumonias, croup and bronchiolitis, dengue fever, leishmaniasis, Staphylococcus aureus, groups A and B Streptococcus, Shigellas and enterotoxigenic Escherichia coli, to only name a few. These are the current targets of vaccines under development, a great many of which will hopefully reach the market within the coming 10 years. The development of preventive vaccines against chronic diseases such as AIDS and hepatitis C will probably require more time, due to basic science complexities to be overcome first. It is likely that the future will also see an emphasis on therapeutic vaccines targeted against noninfectious diseases such as cancers (lung, skin, prostate, etc) and metabolic or neurologic diseases (atherosclerosis, Alzheimer's disease). This review will focus on examples of preventive vaccines under development that target infectious diseases with a heavy global burden on public health. PMID:19446671

  10. Nanoparticles for transcutaneous vaccination

    PubMed Central

    Hansen, Steffi; Lehr, Claus‐Michael

    2012-01-01

    Summary The living epidermis and dermis are rich in antigen presenting cells (APCs). Their activation can elicit a strong humoral and cellular immune response as well as mucosal immunity. Therefore, the skin is a very attractive site for vaccination, and an intradermal application of antigen may be much more effective than a subcutaneous or intramuscular injection. However, the stratum corneum (SC) is a most effective barrier against the invasion of topically applied vaccines. Products which have reached the stage of clinical testing, avoid this problem by injecting the nano‐vaccine intradermally or by employing a barrier disrupting method and applying the vaccine to a relatively large skin area. Needle‐free vaccination is desirable from a number of aspects: ease of application, improved patient acceptance and less risk of infection among them. Nanocarriers can be designed in a way that they can overcome the SC. Also incorporation into nanocarriers protects instable antigen from degradation, improves uptake and processing by APCs, and facilitates endosomal escape and nuclear delivery of DNA vaccines. In addition, sustained release systems may build a depot in the tissue gradually releasing antigen which may avoid booster doses. Therefore, nanoformulations of vaccines for transcutaneous immunization are currently a very dynamic field of research. Among the huge variety of nanocarrier systems that are investigated hopes lie on ultra‐flexible liposomes, superfine rigid nanoparticles and nanocarriers, which are taken up by hair follicles. The potential and pitfalls associated with these three classes of carriers will be discussed. PMID:21854553

  11. Vaccines, viruses, and voodoo.

    PubMed

    Borchers, Andrea T; Keen, Carl L; Shoenfeld, Yehuda; Silva, Joseph; Gershwin, M Eric

    2002-01-01

    Vaccinations are invaluable in protection from a wide variety of diseases that can cause substantial morbidity and mortality. Although a rare complication of vaccination, autoimmune disorders represent one of these morbidities. Recently, widespread public concern has arisen from case reports suggesting that--similar to what has been observed after natural viral infections--there might be an association between specific immunizations and autoimmune diseases. Herein we address the biological plausibility of such a connection, focusing particularly on the examples of hepatitis B, rubella, and measles-mumps-rubella (MMR) vaccinations, and the autoimmune diseases they are potentially associated with. Our review of the available data suggests that, for the general population, the risk: benefit ratio is overwhelmingly in favor of vaccinations. However, the possibility cannot be ruled out that, in genetically susceptible individuals, vaccination can result in the unmasking of an autoimmune disease triggered by the immunization. We also critically examine the existing data suggesting a link between immunization against MMR and autism, and briefly discuss the controversial evidence pointing to a possible relationship between mercury exposure from vaccines and autistic disorders. There is a continued urgent need for rigorously designed and executed studies addressing these potential associations, although the use of vaccinations remains a critical public health tool for protection against infectious disease. PMID:12530114

  12. [Vaccinations in respiratory medicine].

    PubMed

    Lode, H M; Stahlmann, R

    2015-09-01

    Vaccinations are the most successful and cost-effective measures for prevention of infections. Important pathogens of respiratory tract infections (e.g. influenza viruses and pneumococci) can be effectively treated by vaccinations. The seasonal trivalent and recently now quadrivalent influenza vaccines include antigens from influenza A and B type viruses, which have to be modified annually oriented to the circulating strains. The effective protection by influenza vaccination varies considerably (too short protection time, mismatch); therefore, administration late in the year is the best approach (November/December). Two pneumococcal vaccines are recommended for adults: the over 30-year-old 23-valent polysaccharide vaccine (PPV23) and the 4-year-old 13-valent conjugate vaccine (PCV13). The immunological and clinical efficacy of PPV23 is controversially discussed; however, a moderate reduction of invasive pneumococcal infections is widely accepted. The PCV13 stimulates a T-cell response and has currently demonstrated its clinical efficacy in an impressive study (CAPiTA). The problem of PCV13 is the relatively limited coverage of only 47% of the currently circulating invasive pneumococcal serotypes. PMID:26330051

  13. [Acute bacterial exacerbation of chronic obstructive pulmonary disease and biofilm].

    PubMed

    Legnani, Delfino

    2009-07-01

    The lower respiratory tract of patients affected by COPD is constantly colonized by pathogenic microrganisms such as H. influenzae, M. catarrhalis and S. pneumoniae. Role of bacterial colonization of big and small airways in patients affected by COPD is still unclear but it is likely to play a role in directly or indirectly maintaining the vicious circle of infection/inflammation. Colonizer pathogens are capable to stimulate mucus production, to alter the ciliary function by inducing dyskinesia and stasis; in addition, they represent a strong stimulus for neutrophils to come in the airways, which release elastase that, in turn, inhibit the mucus-ciliary function. The same pathogens are responsible for epithelial damage and chronic inflammation, by releasing neutrophilic elastase, leading to the damage progression and obstruction. Recent studies have also shown that infection sustained by H. influenzae is not limited to bronchial mucosa, i.e. surface epithelial cells, but that the pathogen is capable to penetrate cells, so spreading the infection in sub-epithelial cellular layers. In addition, the ability to produce biofilm is another possible defence mechanism which allows them to grow and colonise. Such a mechanism could in part explain the lack of response to antimicrobials and contribute to stimulation of parenchymal inflammatory response, the cause of pathological-anatomic damage which occurs in COPD. The impossibility to eradicate chronic infection and bacterial exacerbations of COPD are likely the elements that promt and worsen obstruction, so determining the disease's progression. PMID:19696555

  14. COPD Exacerbation Biomarkers Validated Using Multiple Reaction Monitoring Mass Spectrometry

    PubMed Central

    Leung, Janice M.; Chen, Virginia; Hollander, Zsuzsanna; Dai, Darlene; Tebbutt, Scott J.; Aaron, Shawn D.; Vandemheen, Kathy L.; Rennard, Stephen I.; FitzGerald, J. Mark; Woodruff, Prescott G.; Lazarus, Stephen C.; Connett, John E.; Coxson, Harvey O.; Miller, Bruce; Borchers, Christoph; McManus, Bruce M.; Ng, Raymond T.; Sin, Don D.

    2016-01-01

    Background Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) result in considerable morbidity and mortality. However, there are no objective biomarkers to diagnose AECOPD. Methods We used multiple reaction monitoring mass spectrometry to quantify 129 distinct proteins in plasma samples from patients with COPD. This analytical approach was first performed in a biomarker cohort of patients hospitalized with AECOPD (Cohort A, n = 72). Proteins differentially expressed between AECOPD and convalescent states were chosen using a false discovery rate <0.01 and fold change >1.2. Protein selection and classifier building were performed using an elastic net logistic regression model. The performance of the biomarker panel was then tested in two independent AECOPD cohorts (Cohort B, n = 37, and Cohort C, n = 109) using leave-pair-out cross-validation methods. Results Five proteins were identified distinguishing AECOPD and convalescent states in Cohort A. Biomarker scores derived from this model were significantly higher during AECOPD than in the convalescent state in the discovery cohort (p<0.001). The receiver operating characteristic cross-validation area under the curve (CV-AUC) statistic was 0.73 in Cohort A, while in the replication cohorts the CV-AUC was 0.77 for Cohort B and 0.79 for Cohort C. Conclusions A panel of five biomarkers shows promise in distinguishing AECOPD from convalescence and may provide the basis for a clinical blood test to diagnose AECOPD. Further validation in larger cohorts is necessary for future clinical translation. PMID:27525416

  15. Exacerbations of childhood asthma and ozone pollution in Atlanta

    SciTech Connect

    White, M.C.; Etzel, R.A.; Lloyd, C. ); Wilcox, W.D. )

    1994-04-01

    Asthma prevalence and mortality due to asthma have been increasing during the last decade, and both the rates and the increases in rates have been higher for blacks than whites and higher for children than adults. Whether environmental factors such as air pollution contribute to these increases is unknown. The purpose of this study was to examine the relationship between emergency visits to a hospital for childhood asthma and exposure to ozone in an indigent, predominantly black population. Data were collected by abstracting clinical records for all children with asthma or reactive airway disease in one public hospital during the summer of 1990. From June 1, 1990, to August 31, 1990, 609 visits were made by children aged 1 to 16 years to an emergency clinic for treatment of asthma or reactive airway disease. Monitoring data indicated that maximum ozone levels equalled or exceeded 0.11 ppm on 6 days during the study period. The average number of visits for asthma or reactive airway disease was 37% higher on the days after those 6 days (from 6:00 PM to 6:00 PM the next day) than on other days (95% Cl, RR = 1.02-1.73). The results of the study suggest that among black children from low-income families, asthma may be exacerbated following periods of high ozone pollution. 45 refs., 1 fig., 4 tabs.

  16. [Possibility of exacerbation of allergy by lunar regolith].

    PubMed

    Horie, Masanori; Kambara, Tatsunori; Kuroda, Etsushi; Miki, Takeo; Honma, Yoshiyuki; Aoki, Shigeru; Morimoto, Yasuo

    2012-09-01

    Japan, U.S.A. and other foreign space agencies have plans for the construction of a lunar base and long-term stay of astronauts on the moon. The surface of the moon is covered by a thick layer of soil that includes fine particles called "lunar regolith", which is formed by meteorite impact and space weathering. Risk assessment of particulate matter on the moon is important for astronauts working in microgravity on the moon. However, there are few investigations about the biological influences of lunar regolith. Especially, there is no investigation about allergic activity to lunar regolith. The main chemical components of lunar regolith are SiO2, Al2O3, CaO, FeO, etc. Of particular interest, approximately 50% of lunar regolith consists of SiO2. There is a report that the astronauts felt hay fever-like symptoms from the inhalation of the lunar regolith. Yellow sand, whose chemical components are similar to lunar regolith, enhances allergenic reactions, suggesting the possibility that lunar regolith has an adjuvant-like activity. Although intraperitoneal administration of lunar regolith with ovalbumin to mouse did not show enhancement of allergenic reactions, further evaluation of lunar regolith's potential to exacerbate the effects of allergies is essential for development of the moon. PMID:23035343

  17. A Systematic Review of Diagnostic Biomarkers of COPD Exacerbation

    PubMed Central

    Chen, Yu-Wei Roy; Leung, Janice M.; Sin, Don D.

    2016-01-01

    The aims of this systematic review were to determine which blood-based molecules have been evaluated as possible biomarkers to diagnose chronic obstructive pulmonary disease (COPD) exacerbations (AECOPD) and to ascertain the quality of these biomarker publications. Patients of interest were those that have been diagnosed with COPD. MEDLINE, EMBASE, and CINAHL databases were searched systematically through February 2015 for publications relating to AECOPD diagnostic biomarkers. We used a modified guideline for the REporting of tumor MARKer Studies (mREMARK) to assess study quality. Additional components of quality included the reporting of findings in a replication cohort and the use of receiver-operating characteristics area-under-the curve statistics in evaluating performance. 59 studies were included, in which the most studied biomarkers were C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). CRP showed consistent elevations in AECOPD compared to control subjects, while IL-6 and TNF-α had variable statistical significance and results. mREMARK scores ranged from 6 to 18 (median score of 13). 12 articles reported ROC analyses and only one study employed a replication cohort to confirm biomarker performance. Studies of AECOPD diagnostic biomarkers remain inconsistent in their reporting, with few studies employing ROC analyses and even fewer demonstrating replication in independent cohorts. PMID:27434033

  18. Exacerbated graft-versus-host disease in Pirb-/- mice.

    PubMed

    Nakamura, Akira; Kobayashi, Eiji; Takai, Toshiyuki

    2004-06-01

    Immune responses are often regulated by opposing receptor pairs that recognize the same ligand but deliver either activating or inhibitory signals. Paired immunoglobulin-like receptors (PIRs) expressed on B cells and myeloid cells comprise a major histocompatibility complex class I recognition system that regulates the responsiveness of these cells. Here, activating PIR-A and inhibitory PIR-B bound various mouse major histocompatibility complex class I (H-2) molecules, and in vitro H-2 tetramer stimulation of PIR-B on B cells or PIR-A on macrophages induced intracellular phosphotyrosine signaling. After transfer of allogeneic splenocytes into PIR-B-deficient mice, the mice showed exacerbated graft-versus-host disease, which was due to augmented activation of recipient dendritic cells with concomitant upregulation of PIR-A and increased interferon-gamma production. PIR-A-induced dendritic cell activation also led to increased proliferation of donor cytotoxic T cells. Thus, PIR-A and PIR-B are counteracting receptors that are essential for successful tissue transplantation and may regulate irrelevant reaction to autologous tissues in a constitutive way in physiological conditions. PMID:15146181

  19. RCAN1 Overexpression Exacerbates Calcium Overloading-Induced Neuronal Apoptosis

    PubMed Central

    Herculano, Bruno; Song, Weihong

    2014-01-01

    Down Syndrome (DS) patients develop characteristic Alzheimer's Disease (AD) neuropathology after their middle age. Prominent neuronal loss has been observed in the cortical regions of AD brains. However, the underlying mechanism leading to this neuronal loss in both DS and AD remains to be elucidated. Calcium overloading and oxidative stress have been implicated in AD pathogenesis. Two major isoforms of regulator of calcineurin 1 (RCAN1), RCAN1.1 and RCAN1.4, are detected in human brains. In this report we defined the transcriptional regulation of RCAN1.1 and RCAN1.4 by two alternative promoters. Calcium overloading upregulated RCAN1.4 expression by activating RCAN1.4 promoter through calcineurin-NFAT signaling pathway, thus forming a negative feedback loop in isoform 4 regulation. Furthermore, RCAN1.4 overexpression exacerbated calcium overloading-induced neuronal apoptosis, which was mediated by caspase-3 apoptotic pathway. Our results suggest that downregulating RCAN1.4 expression in neurons could be beneficial to AD patients. PMID:24751678

  20. Emerging Role of Spinal Cord TRPV1 in Pain Exacerbation

    PubMed Central

    Choi, Seung-In; Lim, Ji Yeon; Yoo, Sungjae; Kim, Hyun; Hwang, Sun Wook

    2016-01-01

    TRPV1 is well known as a sensor ion channel that transduces a potentially harmful environment into electrical depolarization of the peripheral terminal of the nociceptive primary afferents. Although TRPV1 is also expressed in central regions of the nervous system, its roles in the area remain unclear. A series of recent reports on the spinal cord synapses have provided evidence that TRPV1 plays an important role in synaptic transmission in the pain pathway. Particularly, in pathologic pain states, TRPV1 in the central terminal of sensory neurons and interneurons is suggested to commonly contribute to pain exacerbation. These observations may lead to insights regarding novel synaptic mechanisms revealing veiled roles of spinal cord TRPV1 and may offer another opportunity to modulate pathological pain by controlling TRPV1. In this review, we introduce historical perspectives of this view and details of the recent promising results. We also focus on extended issues and unsolved problems to fully understand the role of TRPV1 in pathological pain. Together with recent findings, further efforts for fine analysis of TRPV1's plastic roles in pain synapses at different levels in the central nervous system will promote a better understanding of pathologic pain mechanisms and assist in developing novel analgesic strategies. PMID:26885404

  1. Infection with Porphyromonas gingivalis Exacerbates Endothelial Injury in Obese Mice

    PubMed Central

    Inubushi, Toshihiro; Kitagawa, Masae; Furusho, Hisako; Ando, Toshinori; Ayuningtyas, Nurina Febriyanti; Nagasaki, Atsuhiro; Ishihara, Kazuyuki; Tahara, Hidetoshi; Kozai, Katsuyuki; Takata, Takashi

    2014-01-01

    Background A number of studies have revealed a link between chronic periodontitis and cardiovascular disease in obese patients. However, there is little information about the influence of periodontitis-associated bacteria, Porphyromonas gingivalis (Pg), on pathogenesis of atherosclerosis in obesity. Methods In vivo experiment: C57BL/6J mice were fed with a high-fat diet (HFD) or normal chow diet (CD), as a control. Pg was infected from the pulp chamber. At 6 weeks post-infection, histological and immunohistochemical analysis of aortal tissues was performed. In vitro experiment: hTERT-immortalized human umbilical vein endothelial cells (HuhT1) were used to assess the effect of Pg/Pg-LPS on free fatty acid (FFA) induced endothelial cells apoptosis and regulation of cytokine gene expression. Results Weaker staining of CD31 and increased numbers of TUNEL positive cells in aortal tissue of HFD mice indicated endothelial injury. Pg infection exacerbated the endothelial injury. Immunohistochemically, Pg was detected deep in the smooth muscle of the aorta, and the number of Pg cells in the aortal wall was higher in HFD mice than in CD mice. Moreover, in vitro, FFA treatment induced apoptosis in HuhT1 cells and exposure to Pg-LPS increased this effect. In addition, Pg and Pg-LPS both attenuated cytokine production in HuhT1 cells stimulated by palmitate. Conclusions Dental infection of Pg may contribute to pathogenesis of atherosclerosis by accelerating FFA-induced endothelial injury. PMID:25334003

  2. Acute exacerbation of idiopathic pulmonary fibrosis: shifting the paradigm.

    PubMed

    Ryerson, Christopher J; Cottin, Vincent; Brown, Kevin K; Collard, Harold R

    2015-08-01

    The goal of this review is to summarise the clinical features, management, and prognosis of acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). AE-IPF has previously been defined based on clinical and radiological features that include the subacute onset of dyspnoea, bilateral ground glass changes on chest high-resolution computed tomography, and the absence of an identifiable aetiology. The annual incidence of AE-IPF is typically reported at 5-15%, but is less common in mild disease. Features of diffuse alveolar damage are present when a biopsy is performed. Idiopathic pulmonary fibrosis (IPF) patients with acute respiratory worsening are often initially treated with high dose corticosteroids and antimicrobials; however, there are no clear data to support these therapies, and the short-term mortality of AE-IPF is ~50%. Recent studies have shown that the features and prognosis of AE-IPF are similar to other causes of acute respiratory worsening, including infection, aspiration, air pollution and mechanical injury to the alveolar epithelium. Based on this emerging evidence, we propose a novel approach to the classification of acute respiratory worsening events in patients with IPF that focuses on clinical and radiological findings consistent with an underlying pathobiology of diffuse alveolar damage. PMID:26232481

  3. Stress Cardiomyopathy in the Setting of COPD Exacerbation

    PubMed Central

    Landefeld, Kevin; Saleh, Qusai; Sander, Gary E.

    2015-01-01

    Introduction. Stress cardiomyopathy, or takotsubo cardiomyopathy, is an acute, reversible left ventricular dysfunction usually initiated by a psychological or physical stress. We report this case of stress cardiomyopathy following a chronic obstructive pulmonary disease exacerbation and the subsequent treatment. Case Description. A 49-year-old white female with a history of chronic obstructive pulmonary disease presented to the emergency room via emergency medical services with worsening severe shortness of breath and productive cough for 2 weeks but denied any chest pain on arrival. On presentation, she was noted to be tachypneic, using her accessory muscles and with bilateral coarse expiratory wheezing on lung auscultation. Initial electrocardiogram demonstrated sinus tachycardia. She was treated with multiple albuterol treatments. Soon afterwards, the course was complicated by hypoxic respiratory failure eventually requiring intubation. Her repeat electrocardiogram showed acute changes consistent with myocardial infarction, and an echocardiograph demonstrated apical akinesia with an ejection fraction of 25% to 30%. The patient was urgently taken for cardiac catheterization, which showed no angiographic evidence of coronary artery disease. Three days after initial presentation, a repeat transthoracic echocardiogram showed overall left ventricular systolic function improvement. Discussion. This case provided a unique look at the difficulty of balancing catecholamines in a patient with bronchospasm and stress cardiomyopathy. PMID:26904708

  4. Food-induced (allergic) arthritis. Inflammatory arthritis exacerbated by milk.

    PubMed

    Panush, R S; Stroud, R M; Webster, E M

    1986-02-01

    Suggestive, but largely unproven, observations have associated arthritis with environmental antigens, including foods. We studied a patient with inflammatory arthritis in a prospective, "blinded," controlled fashion to determine whether her symptoms were associated with food sensitivities. This 52-year-old white woman with 11 years of class I, stage I, active disease, had symptomatic exacerbations allegedly associated with meat, milk, and beans. We observed an increase in symptoms following an unblinded food challenge and then studied her in our clinical research unit. On her normal diet for 6 days, she averaged 30 minutes of morning stiffness, 9 tender joints, 3 swollen joints, 87% subjective assessment (100% = best possible), and 89% examiner assessment. While she was fasting (3 days) or taking Vivonex (2 days), we noted no morning stiffness, tender joint score of 1, swollen joint score of 0, and assessments of 100% (P less than 0.05 versus normal diet). She was then nourished with Vivonex for 33 days without difficulty and challenged in a blinded fashion at mealtimes with lyophilized foods placed into opaque capsules. Four milk challenges (equivalent to greater than or equal to 8 ounces per meal) produced up to 30 minutes of morning stiffness, 14 tender joints, 4 swollen joints, subjective assessment of 85%, and objective assessment of 80% (P less than 0.05 versus fasting-Vivonex), peaking 24-48 hours postchallenge. Placebo and other foods (lettuce and carrots) were without effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3513771

  5. Research toward Malaria Vaccines

    NASA Astrophysics Data System (ADS)

    Miller, Louis H.; Howard, Russell J.; Carter, Richard; Good, Michael F.; Nussenzweig, Victor; Nussenzweig, Ruth S.

    1986-12-01

    Malaria exacts a toll of disease to people in the Tropics that seems incomprehensible to those only familiar with medicine and human health in the developed world. The methods of molecular biology, immunology, and cell biology are now being used to develop an antimalarial vaccine. The Plasmodium parasites that cause malaria have many stages in their life cycle. Each stage is antigenically distinct and potentially could be interrupted by different vaccines. However, achieving complete protection by vaccination may require a better understanding of the complexities of B- and T-cell priming in natural infections and the development of an appropriate adjuvant for use in humans.

  6. Anti-addiction vaccines

    PubMed Central

    Shen, Xiaoyun; Orson, Frank M.

    2011-01-01

    Despite intensive efforts to eradicate it, addiction to both legal and illicit drugs continues to be a major worldwide medical and social problem. Anti-addiction vaccines can produce the antibodies to block the effects of these drugs on the brain, and have great potential to ameliorate the morbidity and mortality associated with illicit drug intoxications. This review provides a current overview of anti-addiction vaccines that are under clinical trial and pre-clinical research evaluation. It also outlines the development challenges, ethical concerns, and likely future intervention for anti-addiction vaccines. PMID:22003367

  7. Hepatitis B vaccination.

    PubMed

    Romanò, Luisa; Paladini, Sara; Galli, Cristina; Raimondo, Giovanni; Pollicino, Teresa; Zanetti, Alessandro R

    2015-01-01

    Hepatitis B virus is a worldwide leading cause of acute and chronic liver disease including cirrhosis and hepatocellular carcinoma. Effective vaccines have been available since the early '80s and vaccination has proved highly successful in reducing the disease burden, the development of the carrier state and the HB-related morbidity and mortality in the countries where vaccination has been implemented.   Neutralizing (protective) antibodies (anti-HBs) induced by vaccination are targeted largely towards the amino acid hydrophilic region, referred to as the common a determinant which is present on the outer protein coat or surface antigen (HBsAg), spanning amino acids 124-149. This provides protection against all HBV genotypes (from A to H) and is responsible for the broad immunity afforded by hepatitis B vaccination. Thus, alterations of residues within this region of the surface antigen may determine conformational changes that can allow replication of the mutated HBV in vaccinated people. An important mutation in the surface antigen region was identified in Italy some 25 years ago in infants born to HBsAg carrier mothers who developed breakthrough infections despite having received HBIG and vaccine at birth. This virus had a point mutation from guanosine to adenosine at nucleotide position 587, resulting in aa substitution from glycine (G) to arginine (R) at position 145 in the a determinant. Since the G145R substitution alters the projecting loop (aa 139-147) of the a determinant, the neutralizing antibodies induced by vaccination are no longer able to recognize the mutated epitope. Beside G145R, other S-gene mutations potentially able to evade neutralizing anti-HBs and infect vaccinated people have been described worldwide. In addition, the emergence of Pol mutants associated with resistance to treatment with nucleos(t)ide analogues can select viruses with crucial changes in the overlapping S-gene, potentially able to alter the S protein immunoreactivity. Thus

  8. Developing vaccines against pandemic influenza.

    PubMed Central

    Wood, J M

    2001-01-01

    Pandemic influenza presents special problems for vaccine development. There must be a balance between rapid availability of vaccine and the safeguards to ensure safety, quality and efficacy of vaccine. Vaccine was developed for the pandemics of 1957, 1968, 1977 and for the pandemic alert of 1976. This experience is compared with that gained in developing vaccines for a possible H5N1 pandemic in 1997-1998. Our ability to mass produce influenza vaccines against a pandemic threat was well illustrated by the production of over 150 million doses of 'swine flu' vaccine in the USA within a 3 month period in 1976. However, there is cause for concern that the lead time to begin vaccine production is likely to be about 7-8 months. Attempts to reduce this time should receive urgent attention. Immunogenicity of vaccines in pandemic situations is compared over the period 1968-1998. A consistent feature of the vaccine trials is the demonstration that one conventional 15 microg haemagglutinin dose of vaccine is not sufficiently immunogenic in naive individuals. Much larger doses or two lower doses are needed to induce satisfactory immunity. There is some evidence that whole-virus vaccines are more immunogenic than split or subunit vaccines, but this needs substantiating by further studies. H5 vaccines appeared to be particularly poor immunogens and there is evidence that an adjuvant may be needed. Prospects for improving the development of pandemic vaccines are discussed. PMID:11779397

  9. Overlapping Synthetic Peptides Encoding TPD52 as Breast Cancer Vaccine in Mice: Prolonged Survival1

    PubMed Central

    Mirshahidi, Saied; Kramer, Victor G.; Whitney, James B.; Essono, Sosthène; Lee, Sandra; Dranoff, Glenn; Anderson, Karen S.; Ruprecht, Ruth M.

    2015-01-01

    Summary Peptide-based vaccines, one of several anti-tumor immunization strategies currently under investigation, can elicit both MHC Class I-restricted (CD8+) and Class II-restricted (CD4+) responses. However, the need to identify specific T-cell epitopes in the context of MHC alleles has hampered the application of this approach. We have tested overlapping synthetic peptides (OSP) representing a tumor antigen as a novel approach that bypasses the need for epitope mapping, since OSP contain all possible epitopes for both CD8+ and CD4+ T cells. Here we report that vaccination of inbred and outbred mice with OSP representing tumor protein D52 (TPD52-OSP), a potential tumor antigen target for immunotherapy against breast, prostate, and ovarian cancer, was safe and induced specific CD8+ and CD4+ T-cell responses, as demonstrated by development of specific cytotoxic T cell (CTL) activity, proliferative responses, interferon (IFN)-γ production and CD107a/b expression in all mice tested. In addition, TPD52-OSP-vaccinated BALB/c mice were challenged with TS/A breast carcinoma cells expressing endogenous TPD52; significant survival benefits were noted in vaccine recipients compared to unvaccinated controls (P < 0.001). Our proof-of-concept data demonstrate the safety and efficacy of peptide library-based cancer vaccines that obviates the need to identify epitopes or MHC backgrounds of the vaccinees. We show that an OSP vaccination approach can assist in the disruption of self-tolerance and conclude that our approach may hold promise for immunoprevention of early-stage cancers in a general population. PMID:19201387

  10. Immunogenicity and safety of the human papillomavirus vaccine in patients with autoimmune diseases: A systematic review.

    PubMed

    Pellegrino, Paolo; Radice, Sonia; Clementi, Emilio

    2015-07-01

    Whereas safety and efficacy of HPV vaccines in healthy women have been shown in several randomised controlled clinical trials and in post marketing analyses, only few data exist in patients affected by autoimmune diseases. These issues are significant as autoimmune conditions are recognised as a risk factor for the persistence of HPV infection. Herein we review and systematise the existing literature to assess immunogenicity and safety of HPV vaccination in patients with autoimmune diseases, including systemic lupus erythematosus and juvenile idiopathic arthritis. The results of our literature revision suggest that the HPV vaccines are efficacious and safe in most of the patients affected by autoimmune diseases. Yet, some points of concern remain to be tackled, including the effects of concomitant therapies, the risk of disease exacerbation and the cost-effectiveness of such immunisation programmes in these populations. PMID:26036945

  11. Paradoxical role of antibodies in dengue virus infections: considerations for prophylactic vaccine development.

    PubMed

    Acosta, Eliana G; Bartenschlager, Ralf

    2016-01-01

    Highly effective prophylactic vaccines for flaviviruses including yellow fever virus, tick-borne encephalitis virus and Japanese encephalitis virus are currently in use. However, the development of a dengue virus (DENV) vaccine has been hampered by the requirement of simultaneous protection against four distinct serotypes and the threat that DENV-specific antibodies might either mediate neutralization or, on the contrary, exacerbate disease through the phenomenon of antibody-dependent enhancement (ADE) of infection. Therefore, understanding the cellular, biochemical and molecular basis of antibody-mediated neutralization and ADE are fundamental for the development of a safe DENV vaccine. Here we summarize current structural and mechanistic knowledge underlying these phenomena. We also review recent results demonstrating that the humoral immune response triggered during natural DENV infection is able to generate neutralizing antibodies binding complex quaternary epitopes only present on the surface of intact virions. PMID:26577689

  12. 25-Hydroxyvitamin D3-Deficiency Enhances Oxidative Stress and Corticosteroid Resistance in Severe Asthma Exacerbation

    PubMed Central

    Yang, Xiaoqiong; Cheng, Yuanyuan; zhang, Yun; Wang, Xiaoyun; Wang, Xing; Xie, Tao; Li, Guoping; Liu, Zhigang; Zhong, Nanshan

    2014-01-01

    Oxidative stress plays a significant role in exacerbation of asthma. The role of vitamin D in oxidative stress and asthma exacerbation remains unclear. We aimed to determine the relationship between vitamin D status and oxidative stress in asthma exacerbation. Severe asthma exacerbation patients with 25-hydroxyvitamin D3-deficiency (V-D deficiency) or 25-hydroxyvitamin D-sufficiency (V-D sufficiency) were enrolled. Severe asthma exacerbation with V-D-deficiency showed lower forced expiratory volume in one second (FEV1) compared to that with V-D-sufficiency. V-D-deficiency intensified ROS release and DNA damage and increased TNF-α, OGG1 and NFκB expression and NFκB phosphorylation in severe asthma exacerbation. Supplemental vitamin D3 significantly increased the rates of FEV1 change and decreased ROS and DNA damage in V-D-deficiency. Vitamin D3 inhibited LPS-induced ROS and DNA damage and were associated with a decline in TNF-α and NFκB in epithelial cells. H2O2 reduces nuclear translocation of glucocorticoid receptors in airway epithelial cell lines. V-D pretreatment enhanced the dexamethasone-induced nuclear translocation of glucocorticoid receptors in airway epithelial cell lines and monocytes from 25-hydroxyvitamin D3-deficiency asthma patients. These findings indicate that V-D deficiency aggravates oxidative stress and DNA damage, suggesting a possible mechanism for corticosteroid resistance in severe asthma exacerbation. PMID:25380286

  13. Pneumococcal vaccine (image)

    MedlinePlus

    Pneumococcal vaccine is an immunization against Streptococcus pneumoniae , a bacterium that frequently causes meningitis and pneumonia in the elderly, and people with chronic illnesses. Pneumococcal pneumonia accounts for 10 ...

  14. Future of Polio Vaccines

    PubMed Central

    2009-01-01

    Summary Over the past half-century, global use of highly effective vaccines against poliomyelitis brought this disease to the brink of elimination. Mounting evidence argues that a high level of population immunity must be maintained to preserve a polio-free status of the entire world after wild poliovirus circulation is stopped. Shifting factors in the risk-benefit-cost equation favor the creation of new poliovirus vaccines to be used in the foreseeable future. Genetically stable attenuated virus strains could be developed for an improved oral poliovirus vaccine, but proving their safety and efficacy would be impractical because of the enormous size of the clinical trials required. New versions of inactivated poliovirus vaccine (IPV) that could be used globally should be developed. An improved IPV must be efficacious, inexpensive, safe to manufacture, and easy to administer. Combination products containing IPV along with other protective antigens should become part of routine childhood immunizations around the world. PMID:19545205

  15. Antibacterials: A sweet vaccine

    NASA Astrophysics Data System (ADS)

    Bundle, David

    2016-03-01

    Vaccination with a synthetic glycoconjugate, in combination with the administration of an inhibitor that blocks capsular polysaccharide synthesis in bacteria, could offer an alternative route to combat bacterial infections.

  16. Recombinant vaccines against leptospirosis.

    PubMed

    Dellagostin, Odir A; Grassmann, André A; Hartwig, Daiane D; Félix, Samuel R; da Silva, Éverton F; McBride, Alan J A

    2011-11-01

    Leptospirosis is an important neglected infectious disease that occurs in urban environments, as well as in rural regions worldwide. Rodents, the principal reservoir hosts of pathogenic Leptospira spp., and other infected animals shed the bacteria in their urine. During occupational or even recreational activities, humans that come into direct contact with infected animals or with a contaminated environment, particularly water, are at risk of infection. Prevention of urban leptospirosis is largely dependent on sanitation measures that are often difficult to implement, especially in developing countries. Vaccination with inactivated whole-cell preparations (bacterins) has limited efficacy due to the wide antigenic variation of the pathogen. Intensive efforts towards developing improved recombinant vaccines are ongoing. During the last decade, many reports on the evaluation of recombinant vaccines have been published. Partial success has been obtained with some surface-exposed protein antigens. The combination of protective antigens and new adjuvants or delivery systems may result in the much-needed effective vaccine. PMID:22048111

  17. Ingredients of Vaccines

    MedlinePlus

    ... more effective. Common substances found in vaccines include: Aluminum gels or salts of aluminum which are added as adjuvants to help the ... December 2003, pp. 1394-1397 ...quantities of mercury, aluminum, formaldehyde, human serum albumin, antibiotics, and yeast proteins ...

  18. Your child's first vaccines

    MedlinePlus

    ... or more of these vaccines today: [ ] DTaP [ ] Hib [ ] Hepatitis B [ ] Polio [ ] PCV13 (Provider: Check appropriate boxes) 1. Why ... are at greatest risk for Hib disease. 5. Hepatitis B Signs and symptoms include tiredness, diarrhea and vomiting, ...

  19. Tetanus, Diphtheria (Td) Vaccine

    MedlinePlus

    Tenivac® (as a combination product containing Diphtheria, Tetanus Toxoids) ... Why get vaccinated?Tetanus and diphtheria are very serious diseases. They are rare in the United States today, but people who do become ...

  20. Vaccines (immunizations) - overview

    MedlinePlus

    ... has NOT shown any link between thimerosal and autism or other medical problems. Allergic reactions are rare ... in vaccines is not associated with risk of autism. J Pediatr. 2013;164:561-567. PMID: 23545349 ...

  1. Substance Abuse Vaccines

    PubMed Central

    Orson, Frank M.; Kinsey, Berma M.; Singh, Rana A. K.; Wu, Yan; Gardner, Tracie; Kosten, Thomas R.

    2008-01-01

    Conventional substance abuse treatments have only had limited success for drugs such as cocaine, nicotine, methamphetamine, and phencyclidine. New approaches, including vaccination to block the effects of these drugs on the brain, are in advanced stages of development. Although several potential mechanisms for the effects of anti-drug vaccines have been suggested, the most straightforward and intuitive mechanism involves binding of the drug by antibodies in the bloodstream, thereby blocking entry and/or reducing the rate of entry of the drug into the central nervous system. The benefits of such antibodies on drug pharmacodynamics will be influenced by both the quantitative and the qualitative properties of the antibodies. The sum of these effects will determine the success of the clinical applications of anti-drug vaccines in addiction medicine. This review will discuss these issues and present the current status of vaccine development for nicotine, cocaine, methamphetamine, phencyclidine, and morphine. PMID:18991962

  2. National Vaccine Program Office

    MedlinePlus

    ... collaboration and coordination among federal agencies and other stakeholders whose mandate is to help reduce the burden ... how NVPO works with federal and non-federal stakeholders to continually assess and strengthen vaccine safety efforts. ...

  3. [Development of new vaccines].

    PubMed

    González-Romo, Fernando; Picazo, Juan J

    2015-10-01

    Recent and important advances in the fields of immunology, genomics, functional genomics, immunogenetics, immunogenomics, bioinformatics, microbiology, genetic engineering, systems biology, synthetic biochemistry, proteomics, metabolomics and nanotechnology, among others, have led to new approaches in the development of vaccines. The better identification of ideal epitopes, the strengthening of the immune response due to new adjuvants, and the search of new routes of vaccine administration, are good examples of advances that are already a reality and that will favour the development of more vaccines, their use in indicated population groups, or its production at a lower cost. There are currently more than 130 vaccines are under development against the more wished (malaria or HIV), difficult to get (CMV or RSV), severe re-emerging (Dengue or Ebola), increasing importance (Chagas disease or Leishmania), and nosocomial emerging (Clostridium difficile or Staphylococcus aureus) infectious diseases. PMID:26341041

  4. HPV Vaccine and Pregnancy

    MedlinePlus

    ... 16/18 vaccine: a combined analysis of five randomized controlled trials. Obstet Gynecol 114(6):1179-1188. ... types 16 and 18: pooled analysis of two randomized clinical trials. BMJ 340:C712. Winckworth LC and ...

  5. Vaccines and Thimerosal

    MedlinePlus

    ... cause any harm. Thimerosal prevents the growth of bacteria in vaccines. Thimerosal is added to vials of ... dose vials) to prevent growth of germs, like bacteria and fungi. Introduction of bacteria and fungi has ...

  6. Tetanus, Diphtheria (Td) Vaccine

    MedlinePlus

    Tenivac® (as a combination product containing Diphtheria, Tetanus Toxoids) ... Why get vaccinated?Tetanus and diphtheria are very serious diseases. They are rare in the United States today, but people who do become infected often have severe ...

  7. Governments, off-patent vaccines, smallpox and universal childhood vaccination.

    PubMed

    Music, Stanley

    2010-01-22

    WHO is now celebrating more than 30 years of freedom from smallpox. What was originally seen as a victory over an ancient scourge can now be viewed as an epidemiologically driven programme to overcome governmental inertia and under-achievement in delivering an off-patent vaccine. Though efforts are accelerating global vaccine use, a plea is made to push the world's governments to commit to universal childhood vaccination via a proposed new programme. The latter should begin by exploiting a long list of ever more affordable off-patent vaccines, vaccines that can virtually eliminate the bulk of the world's current vaccine-preventable disease burden. PMID:19699330

  8. Intradermal Hepatitis B Vaccine

    PubMed Central

    Ruddock, David G.S.; Dickson, Annie

    1992-01-01

    Intramuscular administration of hepatitis B (HB) vaccine is safe and efficacious, but its cost has limited its availability. In this pilot study, 49 of 56 participants who received 2 μg of intradermal (ID) HB vaccine (one tenth the intramuscular dose) at the beginning of administration, at 1 month, and at 6 months developed protective levels of antibody to HB surface antigen. Although questions remain, the cost savings of this technique make it worth considering. PMID:21229118

  9. Trends in vaccine adjuvants.

    PubMed

    Schijns, Virgil E J C; Lavelle, Ed C

    2011-04-01

    Adjuvants are essential components of most clinically used vaccines. This is because the majority of nonliving vaccines are relatively poor inducers of adaptive immunity unless effective adjuvants are co-administered. Aluminum salts (alum) have been used as adjuvants with great success for almost a century and have been particularly effective at promoting protective humoral immunity. However, alum is not optimally effective for diseases where cell-mediated immunity is required for protection. Furthermore, adjuvants including oil-in-water emulsions have shown improved efficacy for avian influenza protection suggesting that even for diseases where humoral immunity can confer protection, there is scope for developing improved adjuvants. There have been major developments in antigen discovery over the past decade, which has accelerated the vaccine development process for new indications and this demands a new generation of adjuvants that can drive and specifically direct the desired immune responses. A number of systems are under investigation that combine different types of adjuvants into specific formulations with greater activity. Additionally, targeting of vaccines to specific immune cells shows great promise. In the case of cancer and chronic infectious diseases, it may be difficult to develop effective vaccines without blocking immune regulatory pathways, which impede cell-mediated responses. However, increased understanding of immunology and particularly the innate immune system is informing vaccine adjuvant research and consequently driving the development of novel and specifically directed vaccine adjuvant strategies. In this article we address the importance of adjuvants in vaccine development, the known mode of action of specific adjuvants and recent developments in this important field. PMID:21506650

  10. Vaccine myths and misconceptions.

    PubMed

    Clift, Kathy; Rizzolo, Denise

    2014-08-01

    Communicable diseases are on the rise worldwide. Some of the increase in prevalence of these nearly eradicated diseases is due to a decrease in vaccination rates. This decrease is primarily due to parental concerns over vaccine safety and the increasing rates of autism spectrum disorders. Medical providers must address the growing antivaccine movement and misconceptions about immunizations. Physician assistants are in a unique position to offer evidence-based medical advice and encourage immunizations in order to prevent disease outbreaks. PMID:25003847

  11. [Influenza vaccine and adjuvant].

    PubMed

    Nakayama, Tetsuo

    2011-01-01

    Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine. PMID:22129866

  12. Mucosal delivery of vaccines.

    PubMed

    Del Giudice, G; Pizza, M; Rappuoli, R

    1999-09-01

    Oral delivery represents one of the most pursued approaches for large-scale human vaccination. Due to the different characteristics of mucosal immune response, as compared with systemic response, oral immunization requires particular methods of antigen preparation and selective strategies of adjuvanticity. In this paper, we describe the preparation and use of genetically detoxified bacterial toxins as mucosal adjuvants and envisage the possibility of their future exploitation for human oral vaccines. PMID:10525451

  13. Prevention of COPD exacerbation by lysozyme: a double-blind, randomized, placebo-controlled study

    PubMed Central

    Fukuchi, Yoshinosuke; Tatsumi, Koichiro; Inoue, Hiromasa; Sakata, Yukinori; Shibata, Kai; Miyagishi, Hideaki; Marukawa, Yasuhiro; Ichinose, Masakazu

    2016-01-01

    Background/aim Lysozyme (mucopeptide N-acetyl-muramyl hydrolase) is widely used as a mucolytic and anti-inflammatory agent in Japan. We evaluated the effects of long-term lysozyme administration on COPD exacerbation. Methods In a 1-year, randomized, double-blind, placebo-controlled, parallel trial, patients with moderate-to-severe COPD and one or more episodes of COPD exacerbation in the previous year before enrollment were selected. Lysozyme (270 mg) or placebo was administered orally for 52 weeks as an add-on to the standard therapies such as bronchodilators. COPD exacerbation, pulmonary function, and COPD assessment test scores were analyzed. An exacerbation was defined as worsening of more than one symptom of COPD (cough, sputum volume, purulent sputum, or breathlessness) leading to a change in medication. The primary endpoint was exacerbation rate. Results A total of 408 patients were randomly assigned to the lysozyme and placebo groups. The baseline characteristics were similar between the two groups. The exacerbation rate was not significantly different between the two groups (1.4 vs 1.2; P=0.292, Poisson regression). However, a subgroup analysis showed that lysozyme might reduce exacerbation rate in patients with airway-dominant phenotype (1.2 vs 1.6). Moreover, the median time to first exacerbation was longer in patients with airway-dominant phenotype in the lysozyme group than that in the placebo group. The levels of improvement in forced expiratory volume in 1 second and COPD assessment test scores were not statistically different between the groups, but were always greater in the lysozyme group than in the placebo group over the 52 weeks of the study. Conclusion The effects of using lysozyme as an add-on to standard COPD therapy were not significantly different compared with placebo and were insufficient to prevent COPD exacerbation. PMID:27143873

  14. 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

  15. Immunomodulatory vaccination in autoimmune disease.

    PubMed

    Urbanek-Ruiz, Irene; Ruiz, Pedro J; Steinman, Lawrence; Fathman, C Garrison

    2002-06-01

    The development of vaccines is arguably the most significant achievement in medicine to date. The practice of innoculation with the fluid from a sore to protect from a disease actually dates back to ancient China; however, with the introduction of Jenner's smallpox vaccine, and greater understanding of the immune system, vaccines have become specific and systematic. Traditional vaccines have used killed pathogens (hepatitis A and the Salk polio vaccines), immunogenic subunits of a given pathogen (hepatitis B subunit vaccine), or live attenuated pathogens (measles, mumps, rubella, Sabin polio vaccines) to generate protective immunity. Currently, a new generation of vaccines that use the genetic material of a pathogen to elicit protective immunity are being developed. Although the most widespread and successful use of vaccines today remains in the arena of infectious diseases, manipulations of immune responses to protect against cancers, neurologic diseases, and autoimmunity are being explored rigorously. PMID:12092460

  16. Addressing the vaccine confidence gap.

    PubMed

    Larson, Heidi J; Cooper, Louis Z; Eskola, Juhani; Katz, Samuel L; Ratzan, Scott

    2011-08-01

    Vaccines--often lauded as one of the greatest public health interventions--are losing public confidence. Some vaccine experts have referred to this decline in confidence as a crisis. We discuss some of the characteristics of the changing global environment that are contributing to increased public questioning of vaccines, and outline some of the specific determinants of public trust. Public decision making related to vaccine acceptance is neither driven by scientific nor economic evidence alone, but is also driven by a mix of psychological, sociocultural, and political factors, all of which need to be understood and taken into account by policy and other decision makers. Public trust in vaccines is highly variable and building trust depends on understanding perceptions of vaccines and vaccine risks, historical experiences, religious or political affiliations, and socioeconomic status. Although provision of accurate, scientifically based evidence on the risk-benefit ratios of vaccines is crucial, it is not enough to redress the gap between current levels of public confidence in vaccines and levels of trust needed to ensure adequate and sustained vaccine coverage. We call for more research not just on individual determinants of public trust, but on what mix of factors are most likely to sustain public trust. The vaccine community demands rigorous evidence on vaccine efficacy and safety and technical and operational feasibility when introducing a new vaccine, but has been negligent in demanding equally rigorous research to understand the psychological, social, and political factors that affect public trust in vaccines. PMID:21664679

  17. HPV vaccines: a controversial issue?

    PubMed Central

    Nicol, A.F.; Andrade, C.V.; Russomano, F.B.; Rodrigues, L.L.S.; Oliveira, N.S.; Provance, D.W.

    2016-01-01

    Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits. PMID:27074168

  18. Diacylglycerol kinase α exacerbates cardiac injury after ischemia/reperfusion.

    PubMed

    Sasaki, Toshiki; Shishido, Tetsuro; Kadowaki, Shinpei; Kitahara, Tatsuro; Suzuki, Satoshi; Katoh, Shigehiko; Funayama, Akira; Netsu, Shunsuke; Watanabe, Tetsu; Goto, Kaoru; Takeishi, Yasuchika; Kubota, Isao

    2014-01-01

    Early coronary reperfusion of the ischemic myocardium is a desired therapeutic goal for the preservation of myocardial function. However, reperfusion itself causes additional myocardium injuries. Activation of the diacylglycerol-protein kinase C (DAG-PKC) cascade has been implicated in the cardioprotective effects occurring after ischemia/reperfusion (I/R). DAG kinase (DGK) controls cellular DAG levels by converting DAG to phosphatidic acid, and may act as an endogenous regulator of DAG-PKC signaling. In the present study, we examined the functional role of DGKα in cardiac injury after I/R in in vivo mouse hearts. We generated transgenic mice with cardiac-specific overexpression of DGKα (DGKα-TG). The left anterior descending coronary artery was transiently occluded for 20 min and reperfused for 24 h in DGKα-TG mice and wild-type littermate (WT) mice. The levels of phosphorylation activity of PKCε, extracellular-signal regulated kinase (ERK) 1/2, and p70 ribosomal S6 kinase (p70S6K) were increased after I/R in WT mouse hearts. However, in DGKα-TG mice, activation of PKCε, ERK1/2, and p70S6K was attenuated compared to WT mice. After 24 h, Evans blue/triphenyltetrazolium chloride double staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining showed that DGKα-TG mice had significantly larger myocardial infarctions and larger numbers of TUNEL-positive cardiomyocytes than WT mice. Echocardiography and cardiac catheterization revealed that left ventricular systolic function was more severely depressed in DGKα-TG mice than in WT mice after I/R. These findings suggest that DGKα exacerbates I/R injury by inhibiting the cardioprotective effects of PKCε, ERK1/2, and p70S6K activation. PMID:23719772

  19. Exposure to Particulate Hexavalent Chromium Exacerbates Allergic Asthma Pathology

    PubMed Central

    Schneider, Brent C.; Constant, Stephanie L.; Patierno, Steven R.; Jurjus, Rosalyn A.; Ceryak, Susan M.

    2011-01-01

    Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. PMID:22178736

  20. Exacerbation of Acetaminophen Hepatotoxicity by the Anthelmentic Drug Fenbendazole

    PubMed Central

    Gardner, Carol R.; Mishin, Vladimir; Laskin, Jeffrey D.; Laskin, Debra L.

    2012-01-01

    Fenbendazole is a broad-spectrum anthelmintic drug widely used to prevent or treat nematode infections in laboratory rodent colonies. Potential interactions between fenbendazole and hepatotoxicants such as acetaminophen are unknown, and this was investigated in this study. Mice were fed a control diet or a diet containing fenbendazole (8–12 mg/kg/day) for 7 days prior to treatment with acetaminophen (300 mg/kg) or phosphate buffered saline. In mice fed a control diet, acetaminophen administration resulted in centrilobular hepatic necrosis and increases in serum transaminases, which were evident within 12 h. Acetaminophen-induced hepatotoxicity was markedly increased in mice fed the fenbendazole-containing diet, as measured histologically and by significant increases in serum transaminase levels. Moreover, in mice fed the fenbendazole-containing diet, but not the control diet, 63% mortality was observed within 24 h of acetaminophen administration. Fenbendazole by itself had no effect on liver histology or serum transaminases. To determine if exaggerated hepatotoxicity was due to alterations in acetaminophen metabolism, we analyzed sera for the presence of free acetaminophen and acetaminophen-glucuronide. We found that there were no differences in acetaminophen turnover. We also measured cytochrome P450 (cyp) 2e1, cyp3a, and cyp1a2 activity. Whereas fenbendazole had no effect on the activity of cyp2e1 or cyp3a, cyp1a2 was suppressed. A prolonged suppression of hepatic glutathione (GSH) was also observed in acetaminophen-treated mice fed the fenbendazole-containing diet when compared with the control diet. These data demonstrate that fenbendazole exacerbates the hepatotoxicity of acetaminophen, an effect that is related to persistent GSH depletion. These findings are novel and suggest a potential drug-drug interaction that should be considered in experimental protocols evaluating mechanisms of hepatotoxicity in rodent colonies treated with fenbendazole. PMID

  1. How climate change will exacerbate global water scarcity

    NASA Astrophysics Data System (ADS)

    Schewe, Jacob; Heinke, Jens; Gerten, Dieter; Haddeland, Ingjerd; Arnell, Nigel; Clark, Douglas; Dankers, Rutger; Eisner, Stephanie; Fekete, Balázs; Kim, Hyungjun; Liu, Xingcai; Masaki, Yoshimitsu; Portmann, Felix; Satoh, Yusuke; Stacke, Tobias; Tang, Qiuhong; Wada, Yoshihide; Wisser, Dominik; Albrecht, Torsten

    2013-04-01

    Water scarcity, in particular the dearth of renewable water resources for agricultural, industrial and domestic purposes, severely impairs food security and economic prosperity in many countries today. Ex- pected future population changes will, in most countries as well as globally, increase water scarcity through increased demand. On the supply side, renewable water resources will be affected by projected changes in precipitation patterns, temperature, and other climate variables. The magnitude and pattern of hydrological changes however depend on complex interactions between climate, biosphere, and surface properties. Here we use a large ensemble of global hydrological models (GHMs) driven by five global climate models (GCMs) in the framework of the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP) to show that climate change is very likely to exacerbate the global water scarcity problem significantly. In particular, the simulation ensemble average projects that beyond a global warming of 1°C above 1980-2010 levels (approx. 1.5°C above pre-industrial), each additional degree of warming confronts an additional 7-10% of global population with a severe (>20%) decrease in water resources. A warming of 3°C is projected to enhance the global increase in absolute water scarcity, expected from population changes alone, by about 25%, together amounting to more 13% (5-30%) of the world population living at less than 500m3 annual runoff per capita by the end of this century. The projected impacts at different levels of global warming are similar across different climate change scenarios, indicating that dependence on the rate of climate change is low. At the same time, the study highlights significant uncertainties associated with these projections, resulting both from the spread among climate projections and from the GHMs.

  2. Exonic Variants Associated with Development of Aspirin Exacerbated Respiratory Diseases

    PubMed Central

    Chang, HunSoo; Park, Jong Sook; Bae, Da-Jeong; Song, Hyun-Ji; Choi, Inseon S.; Kim, Mi-Kyeong; Park, Hea-Sim; Kim, Lyoung Hyo; Namgoong, Suhg; Kim, Ji On; Shin, Hyoung Doo; Park, Choon-Sik

    2014-01-01

    Aspirin-exacerbated respiratory disease (AERD) is one phenotype of asthma, often occurring in the form of a severe and sudden attack. Due to the time-consuming nature and difficulty of oral aspirin challenge (OAC) for AERD diagnosis, non-invasive biomarkers have been sought. The aim of this study was to identify AERD-associated exonic SNPs and examine the diagnostic potential of a combination of these candidate SNPs to predict AERD. DNA from 165 AERD patients, 397 subjects with aspirin-tolerant asthma (ATA), and 398 normal controls were subjected to an Exome BeadChip assay containing 240K SNPs. 1,023 models (210-1) were generated from combinations of the top 10 SNPs, selected by the p-values in association with AERD. The area under the curve (AUC) of the receiver operating characteristic (ROC) curves was calculated for each model. SNP Function Portal and PolyPhen-2 were used to validate the functional significance of candidate SNPs. An exonic SNP, exm537513 in HLA-DPB1, showed the lowest p-value (p = 3.40×10−8) in its association with AERD risk. From the top 10 SNPs, a combination model of 7 SNPs (exm537513, exm83523, exm1884673, exm538564, exm2264237, exm396794, and exm791954) showed the best AUC of 0.75 (asymptotic p-value of 7.94×10−21), with 34% sensitivity and 93% specificity to discriminate AERD from ATA. Amino acid changes due to exm83523 in CHIA were predicted to be “probably damaging” to the structure and function of the protein, with a high score of ‘1’. A combination model of seven SNPs may provide a useful, non-invasive genetic marker combination for predicting AERD. PMID:25372592

  3. Age exacerbates HIV-associated white matter abnormalities.

    PubMed

    Seider, Talia R; Gongvatana, Assawin; Woods, Adam J; Chen, Huaihou; Porges, Eric C; Cummings, Tiffany; Correia, Stephen; Tashima, Karen; Cohen, Ronald A

    2016-04-01

    Both HIV disease and advanced age have been associated with alterations to cerebral white matter, as measured with white matter hyperintensities (WMH) on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), and more recently with diffusion tensor imaging (DTI). This study investigates the combined effects of age and HIV serostatus on WMH and DTI measures, as well as the relationships between these white matter measures, in 88 HIV seropositive (HIV+) and 49 seronegative (HIV-) individuals aged 23-79 years. A whole-brain volumetric measure of WMH was quantified from FLAIR images using a semi-automated process, while fractional anisotropy (FA) was calculated for 15 regions of a whole-brain white matter skeleton generated using tract-based spatial statistics (TBSS). An age by HIV interaction was found indicating a significant association between WMH and older age in HIV+ participants only. Similarly, significant age by HIV interactions were found indicating stronger associations between older age and decreased FA in the posterior limbs of the internal capsules, cerebral peduncles, and anterior corona radiata in HIV+ vs. HIV- participants. The interactive effects of HIV and age were stronger with respect to whole-brain WMH than for any of the FA measures. Among HIV+ participants, greater WMH and lower anterior corona radiata FA were associated with active hepatitis C virus infection, a history of AIDS, and higher current CD4 cell count. Results indicate that age exacerbates HIV-associated abnormalities of whole-brain WMH and fronto-subcortical white matter integrity. PMID:26446690

  4. Growth hormone resistance exacerbates cholestasis-induced murine liver fibrosis

    PubMed Central

    Stiedl, Patricia; McMahon, Robert; Blaas, Leander; Stanek, Victoria; Svinka, Jasmin; Grabner, Beatrice; Zollner, Gernot; Kessler, Sonja M.; Claudel, Thierry; Müller, Mathias; Mikulits, Wolfgang; Bilban, Martin; Esterbauer, Harald; Eferl, Robert; Haybaeck, Johannes; Trauner, Michael; Casanova, Emilio

    2016-01-01

    Growth hormone (GH) resistance has been associated with liver cirrhosis in humans but its contribution to the disease remains controversial. In order to elucidate whether GH resistance plays a causal role in the establishment and development of liver fibrosis, or rather represents a major consequence thereof, we challenged mice lacking the Growth hormone receptor gene (Ghr-/-, a model for GH resistance) by crossing them with Mdr2 knockout mice (Mdr2-/-), a mouse model of inflammatory cholestasis and liver fibrosis. Ghr-/-;Mdr2-/- mice showed elevated serum markers associated with liver damage and cholestasis, extensive bile duct proliferation and increased collagen deposition relative to Mdr2 -/- mice, thus suggesting a more severe liver fibrosis phenotype. Additionally, Ghr-/-;Mdr2-/- mice had a pronounced down-regulation of hepato-protective genes Hnf6, Egfr and Igf-1, and significantly increased levels of ROS and apoptosis in hepatocytes, compared to control mice. Moreover, single knockout mice (Ghr-/-) fed with a diet containing 1% cholic acid displayed an increase in hepatocyte ROS production, hepatocyte apoptosis and bile infarcts compared to their wildtype littermates, indicating that loss of Ghr renders hepatocytes more susceptible to toxic bile acid accumulation. Surprisingly, and despite their severe fibrotic phenotype, Ghr-/-;Mdr2-/- mice displayed a significant decrease in tumour incidence compared to Mdr2-/- mice, indicating that loss of Ghr signaling may slow the progression from fibrosis/cirrhosis to cancer in the liver. Conclusion Our findings suggest that GH resistance dramatically exacerbates liver fibrosis in a mouse model of inflammatory cholestasis, therefore suggesting that GH resistance plays a causal role in the disease and provides a novel target for the development of liver fibrosis treatments. PMID:25179284

  5. Influenza vaccination for patients with chronic obstructive pulmonary disease: understanding immunogenicity, efficacy and effectiveness.

    PubMed

    Sanei, Farzaneh; Wilkinson, Tom

    2016-08-01

    Influenza infection is an important cause of global mortality and morbidity with the greatest impact on older people and those with chronic disease. Patients with chronic obstructive pulmonary disease (COPD) are particularly vulnerable to influenza, with evidence for increased incidence and severity of infection. In this patient group influenza is associated with exacerbations and pneumonia which result in a significant healthcare burden and premature mortality. Influenza vaccination and in particular the use of the seasonal trivalent influenza vaccine (TIV) is recommended for patients with COPD. The evidence base for its effects in this population is, however, limited. Available data suggest that immunogenicity is variable in COPD but the underlying mechanisms are not completely understood. The contribution of age, disease severity, comorbidity and treatments to vaccine responses has only been investigated in a limited manner. Existing data suggest that key immune mechanisms governing T- and B-cell responses are adversely affected by these factors. The efficacy of TIV has been studied in a number of small clinical trials which form the basis of a Cochrane review. Here evidence for effect is conflicting depending on individual trial design and inclusions. Overall, TIV offers protection against influenza infection in the trial setting but further studies are required to stratify patients and enable prediction of inadequate responses. Larger-scale clinical studies have largely been observational and have often been conducted in consort with pneumonia vaccination. Overall the mortality benefit of TIV in COPD is suggested by a number studies but the impact on exacerbation prevention is less clear. Influenza vaccination currently plays an important role in disease prevention in COPD. However, we postulate that a more in-depth understanding of mechanisms of response in the context of a highly heterogeneous disease will lead to a more informed approach to vaccination and

  6. Efficacy of intradermal vaccination.

    PubMed

    Hunsaker, B D; Perino, L J

    2001-05-10

    Intradermal (ID) inoculation has been investigated as a means of vaccinating laboratory animals, domestic farm animals, and humans. Various forms of viral, bacterial, parasitic, and fungal antigens have been administered ID, with varying results. This review emphasizes results from studies reporting clinically relevant outcomes such as clinical protection and body weight change following experimental challenge. Antibody titers, cytokines, cellular responses are included as supportive data. Based on the reports reviewed, ID vaccination is a promising alternative to more traditional routes of vaccination. ID vaccination has particular appeal to the beef cattle industry based on recently emphasized quality assurance issues. It is evident that the ultimate test of vaccine efficacy is the ability to protect against clinical disease under natural challenge conditions. We propose that the immune response of ID vaccinated cattle, using clinically relevant outcomes such as morbidity, mortality, average daily gain and feed efficiency, needs to be further investigated to define the value of this potentially effective and practical means of antigen delivery, particularly for domesticated farm animals. PMID:11356246

  7. Lung Cancer – Vaccines

    PubMed Central

    Kelly, Ronan J.; Giaccone, Giuseppe

    2011-01-01

    In lung cancer, early attempts to modulate the immune system via vaccine based therapeutics have to date, been unsuccessful. An improved understanding of tumor immunology has facilitated the production of more sophisticated lung cancer vaccines. It is anticipated, that it will likely require multiple epitopes of a diverse set of genes restricted to multiple haplotypes to generate a truly effective vaccine that is able to overcome the various immunologic escape mechanisms that tumors employ. Other issues to overcome include optimal patient selection, which adjuvant agent to use and how to adequately monitor for an immunological response. This review discusses the most promising vaccination strategies for non small cell lung cancer including the allogeneic tumor cell vaccine belagenpumatucel-L, which is a mixture of 4 allogeneic non small cell lung cancer cell lines genetically modified to secrete an antisense oligonucleotide to TGF-β2 and three other target protein-specific vaccines designed to induce responses against melanoma-associated antigen A3 (MAGE-A3), mucin 1 (MUC1) and epidermal growth factor (EGF). PMID:21952280

  8. Heterologous vaccine effects.

    PubMed

    Saadatian-Elahi, Mitra; Aaby, Peter; Shann, Frank; Netea, Mihai G; Levy, Ofer; Louis, Jacques; Picot, Valentina; Greenberg, Michael; Warren, William

    2016-07-25

    The heterologous or non-specific effects (NSEs) of vaccines, at times defined as "off-target effects" suggest that they can affect the immune response to organisms other than their pathogen-specific intended purpose. These NSEs have been the subject of clinical, immunological and epidemiological studies and are increasingly recognized as an important biological process by a growing group of immunologists and epidemiologists. Much remain to be learned about the extent and underlying mechanisms for these effects. The conference "Off-target effects of vaccination" held in Annecy-France (June 8-10 2015) intended to take a holistic approach drawing from the fields of immunology, systems biology, epidemiology, bioinformatics, public health and regulatory science to address fundamental questions of immunological mechanisms, as well as translational questions about vaccines NSEs. NSE observations were examined using case-studies on live attenuated vaccines and non-live vaccines followed by discussion of studies of possible biological mechanisms. Some possible pathways forward in the study of vaccines NSE were identified and discussed by the expert group. PMID:27312214

  9. Therapeutic Cancer Vaccines.

    PubMed

    Ye, Zhenlong; Li, Zhong; Jin, Huajun; Qian, Qijun

    2016-01-01

    Cancer is one of the major leading death causes of diseases. Prevention and treatment of cancer is an important way to decrease the incidence of tumorigenesis and prolong patients' lives. Subversive achievements on cancer immunotherapy have recently been paid much attention after many failures in basic and clinical researches. Based on deep analysis of genomics and proteomics of tumor antigens, a variety of cancer vaccines targeting tumor antigens have been tested in preclinical and human clinical trials. Many therapeutic cancer vaccines alone or combination with other conventional treatments for cancer obtained spectacular efficacy, indicating the tremendously potential application in clinic. With the illustration of underlying mechanisms of cancer immune regulation, valid, controllable, and persistent cancer vaccines will play important roles in cancer treatment, survival extension and relapse and cancer prevention. This chapter mainly summarizes the recent progresses and developments on cancer vaccine research and clinical application, thus exploring the existing obstacles in cancer vaccine research and promoting the efficacy of cancer vaccine. PMID:27240458

  10. Immunology of BVDV vaccines.

    PubMed

    Ridpath, Julia F

    2013-01-01

    Providing acquired immune protection against infection with bovine viral diarrhea viruses (BVDV) is challenging due to the heterogeneity that exists among BVDV strains and the ability of the virus to infect the fetus and establish persistent infections. Both modified live and killed vaccines have been shown to be efficacious under controlled conditions. Both humoral and cellular immune responses are protective. Following natural infection or vaccination with a modified live vaccine, the majority of the B cell response (as measured by serum antibodies) is directed against the viral proteins E2 and NS2/3, with minor responses against the Erns and E1 proteins. Vaccination with killed vaccines results in serum antibodies directed mainly at the E2 protein. It appears that the major neutralizing epitopes are conformational and are located within the N-terminal half of the E2 protein. While it is thought that the E2 and NS2/3 proteins induce protective T cell responses, these epitopes have not been mapped. Prevention of fetal infections requires T and B cell response levels that approach sterilizing immunity. The heterogeneity that exists among circulating BVDV strains, works against establishing such immunity. Vaccination, while not 100% effective in every individual animal, is effective at the herd level. PMID:22883306

  11. BCG vaccine in Korea.

    PubMed

    Joung, Sun Myung; Ryoo, Sungweon

    2013-07-01

    The anti-tuberculosis Bacille de Calmette et Guérin (BCG) vaccine was developed between 1905 and 1921 at Pasteur Institutes of Lille in France, and was adopted by many countries. BCG strains comprise natural mutants of major virulence factors of Mycobacterium tuberculosis and that BCG sub-strains differ markedly in virulence levels. The tuberculosis became endemic in Korea after the Korean War (1950s). The BCG strain, which was donated by Pasteur Institutes, was brought to Korea in 1955, and the first domestic BCG vaccine was produced by the National Defense Research Institute (NDRI), current Korea Centers for Disease Control and Prevention (KCDC), in 1960. Since 1987, BCG manufacture work was handed over to the Korean Institute of Tuberculosis (KIT), the freeze-dried BCG vaccine was manufactured at a scale required to meet the whole amount of domestic consumption. However, since 2006, the manufacture of BCG vaccine suspended and the whole amount of BCG was imported at this point of time. Now KIT is planning to re-produce the BCG vaccine in Korea under the supervision of KCDC, this will be render great role to National Tuberculosis Control Program (NTP) and provide initiating step for developing new tuberculosis vaccines in Korea. PMID:23858398

  12. Children, the Flu, and the Flu Vaccine

    MedlinePlus

    ... Flu Basics Key Facts about Influenza (Flu) Influenza Viruses Types of Influenza Viruses How the Flu Virus Can Change Symptoms & Complications ... Influenza Vaccines How Flu Vaccines Are Made Selecting Viruses for the Seasonal Influenza Vaccine Vaccine Effectiveness Selected ...

  13. List of Vaccine-Preventable Diseases

    MedlinePlus

    ... Patient Education Programs and Tools VTrckS (Vaccine Tracking System) Immunization Registries (IIS) Vaccines for Children (VFC) Stop Transmission of Polio (STOP) Vaccine Management Business Improvement Project (VMBIP) Global Immunizations & Vaccinations Immunization Program ...

  14. Vaccinations for Adults with HIV Infection

    MedlinePlus

    Vaccinations for Adults with HIV Infection The table below shows which vaccinations you should have to protect your health if ... sure you and your healthcare provider keep your vaccinations up to date. Vaccine Do you need it? ...

  15. Vaccinations for Adults with Hepatitis C Infection

    MedlinePlus

    Vaccinations for Adults with Hepatitis C Infection This table shows which vaccinations you should have to protect your health if ... sure you and your healthcare provider keep your vaccinations up to date. Vaccine Do you need it? ...

  16. Selecting Viruses for the Seasonal Influenza Vaccine

    MedlinePlus

    ... which viruses are selected for use in vaccine production? The influenza viruses in the seasonal flu vaccine ... to get a good vaccine virus for vaccine production? There are a number of factors that can ...

  17. Acute Exacerbation of Idiopathic Pulmonary Fibrosis Following Treatment for Cushing's Syndrome.

    PubMed

    Ohara, Nobumasa; Kaneko, Masanori; Sato, Kazuhiro; Usuda, Hiroyuki; Tanaka, Junta; Maekawa, Takashi; Sasano, Hironobu; Katakami, Hideki; Kaneko, Kenzo; Kamoi, Kyuzi

    2016-01-01

    A 64-year-old Japanese man with mild reticular shadows in both lungs developed a lung tumor causing ectopic Cushing's syndrome. He was prescribed an adrenal inhibitor, which controlled his hypercortisolemia. However, he developed acute exacerbation of idiopathic pulmonary fibrosis (IPF) and died within weeks. Previous studies have suggested a dosage reduction of corticosteroids for IPF as a triggering event for acute exacerbation. The present case suggests that IPF coexisting with Cushing's syndrome may have been exacerbated after the correction of hypercortisolemia. Therefore, close monitoring of cortisol levels along with the clinical course of IPF is required in similar cases that require the correction of hypercortisolemia. PMID:26875965

  18. Development of new peptide-based receptor of fluorescent probe with femtomolar affinity for Cu(+) and detection of Cu(+) in Golgi apparatus.

    PubMed

    Jung, Kwan Ho; Oh, Eun-Taex; Park, Heon Joo; Lee, Keun-Hyeung

    2016-11-15

    Developing fluorescent probes for monitoring intracellular Cu(+) is important for human health and disease, whereas a few types of their receptors showing a limited range of binding affinities for Cu(+) have been reported. In the present study, we first report a novel peptide receptor of a fluorescent probe for the detection of Cu(+). Dansyl-labeled tripeptide probe (Dns-LLC) formed a 1:1 complex with Cu(+) and showed a turn-on fluorescent response to Cu(+) in aqueous buffered solutions. The dissociation constant of Dns-LLC for Cu(+) was determined to be 12 fM, showing that Dns-LLC had more potent binding affinity for Cu(+) than those of previously reported chemical probes for Cu(+). The binding mode study showed that the thiol group of the peptide receptor plays a critical role in potent binding with Cu(+) and the sulfonamide and amide groups of the probe might cooperate to form a complex with Cu(+). Dns-LLC detected Cu(+) selectively by a turn-on response among various biologically relevant metal ions, including Cu(2+) and Zn(2+). The selectivity of the peptide-based probe for Cu(+) was strongly dependent on the position of the cysteine residue in the peptide receptor part. The fluorescent peptide-based probe penetrated the living RKO cells and successfully detected Cu(+) in the Golgi apparatus in live cells by a turn-on response. Given the growing interest in imaging Cu(+) in live cells, a novel peptide receptor of Cu(+) will offer the potential for developing a variety of fluorescent probes for Cu(+) in the field of copper biochemistry. PMID:27208475

  19. How Influenza Vaccination Policy May affect Vaccine Logistics

    PubMed Central

    Assi, Tina-Marie; Rookkapan, Korngamon; Rajgopal, Jayant; Sornsrivichai, Vorasith; Brown, Shawn T.; Welling, Joel S.; Norman, Bryan A.; Connor, Diana L.; Chen, Sheng-I; Slayton, Rachel B.; Laosiritaworn, Yongjua; Wateska, Angela R.; Wisniewski, Stephen R.; Lee, Bruce Y.

    2012-01-01

    Background When policymakers make decision about the target populations and timing of influenza vaccination, they may not consider the impact on the vaccine supply chains, which may in turn affect vaccine availability. Purpose Our goal is to explore the effects on the Thailand vaccine supply chain of introducing influenza vaccines and varying the target populations and immunization time-frames. Methods Utilized our custom-designed software HERMES (Highly Extensible Resource for Modeling Supply Chains), we developed a detailed, computational discrete-event simulation model of the Thailand's National Immunization Program (NIP) supply chain in Trang Province, Thailand., A suite of experiments simulated introducing influenza vaccines for different target populations and over different time-frames prior to and during the annual influenza season. Results Introducing influenza vaccines creates bottlenecks that reduce the availability of both influenza vaccines as well as the other NIP vaccines, with provincial to district transport capacity being the primary constraint. Even covering only 25% of the Advisory Committee on Immunization Practice-recommended population while administering the vaccine over six months hinders overall vaccine availability so that only 62% of arriving patients can receive vaccines. Increasing the target population from 25% to 100% progressively worsens these bottlenecks, while increasing influenza vaccination time - frame from 1 to 6 months decreases these bottlenecks. Conclusion Since the choice of target populations for influenza vaccination and the time-frame to deliver this vaccine can substantially affect the flow of all vaccines, policy-makers may want to consider supply chain effects when choosing target populations for a vaccine. PMID:22537993

  20. [Adverse ocular effects of vaccinations].

    PubMed

    Ness, T; Hengel, H

    2016-07-01

    Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects. PMID:27357302