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Sample records for peptide-based vaccine exacerbates

  1. 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

  2. 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

  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. 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

  15. 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

  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. 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

  5. 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

  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. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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

  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. 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 ...

  7. 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 ...

  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. 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

  14. [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

  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. 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

  19. 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

  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. 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

  2. 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

  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. 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

  5. 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

  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. 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

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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

  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. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  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. 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

  13. 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

  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. 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

  16. 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

  17. 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

  18. 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 ...

  19. 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: ...

  20. 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 ...

  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. 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

  4. 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

  5. [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

  6. 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

  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. 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

  10. 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

  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. 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

  13. 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

  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. 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 ...

  17. 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

  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. 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 ...

  20. 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 ...

  1. 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 ...

  2. 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 ...

  3. 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

  4. 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

  5. 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

  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. 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

  9. 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

  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. 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

  12. 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

  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. 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

  16. 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

  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. 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

  19. 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

  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. 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

  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. 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 ...

  10. 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...

  11. 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.

  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. 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.

  14. 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

  15. 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

  16. 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

  17. 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.

  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. 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 ...

  20. 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

  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. 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 ...

  5. 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 ...

  6. 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 ...

  7. 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 ...

  8. 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 ...

  9. 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) ...

  10. 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 ...

  11. 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 ...

  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.

    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

  16. 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.

  17. 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

  18. 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

  19. 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

  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. 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

  5. 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.

  6. 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

  7. 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

  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. 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

  15. 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

  16. 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…

  17. 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

  18. 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

  19. 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

  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. 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

  9. 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

  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. [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

  12. 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

  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. 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

  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. 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

  10. 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