215. Johanna J Therion*, R.l. Mackie and. Frances M.C. Gilchrist. Animal and Dairy Science Research Instituie,. Private BagXZ,Irene L675, Republic of South Africa. *To whom correspondence should be addressed ...
The insect baculovirus expression system is a valuable tool for the production of vaccine. Many subunit vaccines have been expressed in this system. The first vaccine produced in insect cells for animal use is now in the market. In this study, we reviewed recent progress of animal's vaccine production for different expression ...
Full Text Available Although current influenza vaccines are effective in general, there is an urgent need for the development of new technologies to improve vaccine production timelines, capacities and immunogenicity. Herein, we describe the development of an influenza vaccine technology which enables recombinant production of highly efficient influenza vaccines in bacterial expression systems. The globular head domain of influenza hemagglutinin, comprising most of the protein's neutralizing epitopes, was expressed in E. coli and covalently conjugated to bacteriophage-derived virus-like particles produced independently in E.coli. Conjugate influenza vaccines produced this way were used to immunize mice and found to elicit immune sera with high antibody titers specific for the native influenza hemagglutinin protein and high hemagglutination-inhibition titers. Moreover vaccination with these vaccines induced full protection against lethal challenges with homologous and highly drifted influenza strains.
Deen, Jacqueline; Lopez, Anna Lena; Kanungo, Suman; Wang, Xuan-Yi; Anh, Dang Duc; Tapia, Milagritos; Grais, Rebecca F
There are two internationally available WHO-prequalified oral rotavirus vaccines (Rotarix and RotaTeq), two rotavirus vaccines licensed in India (Rotavac and Rotasiil), one in China (Lanzhou lamb rotavirus vaccine) and one in Vietnam (Rotavin-M1), and several candidates in development. Rotavirus vaccination has been rolled out in Latin American countries and is beginning to be deployed in sub-Saharan African countries but middle- and low-income Asian countries have lagged behind in rotavirus vaccine introduction. We provide a mini-review of the leading newer-generation rotavirus vaccines and compare them with Rotarix and RotaTeq. We discuss how the development and future availability of newer-generation rotavirus vaccines that address the programmatic needs of poorer countries may help scale-up rotavirus vaccination where it is needed.
Watanabe, M; Izumiya, K; Sato, T; Yoshino, K; Nakagawa, N; Ohoishi, M; Hoshino, M
The quality of 14 lots of acellular pertussis-diphtheria-tetanus (AC-PDT) vaccines manufactured by the Kitasato Institute during the period 1987-1990 were investigated. The geometric means of HSU, LPU, and BWDU were 0.078, 0.257, and 7.33 per ml respectively. The potency was higher than 14 IU per ml. These results indicated the consistency of the Kitasato AC-PDT vaccines. The antibody response to the AC-PDT vaccines was measured in primary and secondary vaccinated mice by ELISA. IgG antibody response to FHA and PT was obtained in all immunized mice (P less than 0.001) after the primary injection. In contrast, IgG antibody response to fimbriae 2 showed a significant titer rise (P less than 0.001) after the booster injection. The results indicated that the Kitasato AC-P vaccines consisted of protein, PT and FHA as the major antigens, and a little agglutinogen as the minor antigen.
Yoshikawa, Rokusuke; Sato, Eiji; Miyazawa, Takayuki
All domestic cats have a replication-competent endogenous retrovirus, termed RD-114 virus, in their genome and several feline cell lines produce RD-114 viruses. Recently, we found that a portion of live attenuated feline and canine vaccines produced using feline cell lines was contaminated with infectious RD-114 viruses. In this study, we expanded our survey and examined canine vaccines produced using 'non-feline' cell lines. Consequently, we found two vaccines containing RD-114 viral RNA by reverse transcriptase (RT)-polymerase chain reaction (PCR) and real-time RT-PCR. We also confirmed the presence of infectious RD-114 virus in the vaccines by the LacZ marker rescue assay and PCR to detect proviral DNA in TE671 cells (human rhabdomyosarcoma cells) inoculated with the vaccines. It is impossible to investigate the definitive cause of contamination with RD-114 virus; however, we suspect that a seed canine parvovirus type 2 was contaminated with RD-114 virus, because many canine parvoviruses have been isolated and attenuated using feline cell lines. To exclude RD-114 virus from live attenuated vaccines, we must pay attention to the contamination of seed viruses with RD-114 virus in addition to avoiding feline cell lines producing RD-114 virus when manufacturing vaccines. Copyright © 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.
Rogers, R J; Dimmock, C K; de Vos, A J; Rodwell, B J
Contamination of a batch of tick fever (babesiosis and anaplasmosis) vaccine with bovine leucosis virus (BLV) was detected when a herd, in the final stages of an enzootic bovine leucosis (EBL) accreditation program, developed a large number of seropositive cattle following use of tick fever vaccine. Investigations incriminated a single calf used to produce Anaplasma centrale vaccine from which 13,959 doses were distributed. The failure of this calf to give a positive agar gel immunodiffusion (AGID) test before use was not fully explained. A total of 22,627 cattle from 111 herds receiving contaminated vaccine was tested to validate claims for compensation. Results showed infection rates of 62% and 51.8% in vaccinated dairy and beef cattle, respectively, compared with 6.1% and 1.5% in non-vaccinated cattle in the same herds. The results also indicated that infection did not spread from vaccinated to non-vaccinated in-contact cattle. Heavy reliance is now placed on purchase of calves for vaccine production from EBL accredited-free herds and on transmission tests from the calves to sheep to prevent a recurrence of contamination. The need for a BLV antigen detection test, with the sensitivity of the sheep transmission test but simpler and faster to perform, is evident.
Uchida, Yuko; Takemae, Nobuhiro; Saito, Takehiko
In this study, reverse genetics was applied to produce vaccine candidate strains against highly pathogenic avian influenza viruses (HPAIVs) of the H5N1 subtype. The H5 subtype vaccine strains were generated by a reverse genetics method in a biosafety level 2 facility. The strain contained the HA gene from the H5N1 subtype HPAIV attenuated by genetic modification at the cleavage site, the NA gene derived from the H5N1 subtype HPAI or the H5N3 subtype of avian influenza virus and internal genes from A/Puerto Rico/8/34. Vaccination with an inactivated recombinant virus with oil-emulsion completely protected chickens from a homologous viral challenge with a 640 HAU or 3,200 HAU/vaccination dose. Vaccination with a higher dose of antigen, 3,200 HAU, was effective at increasing survival and efficiently reduced viral shedding even when challenged by a virus of a different HA clade. The feasibility of differentiation of infected from vaccinated animals (DIVA) was demonstrated against a challenge with H5N1 HPAIVs when the recombinant H5N3 subtype viruses were used as the antigens of the vaccine. Our study demonstrated that the use of reverse genetics would be an option to promptly produce an inactivated vaccine with better matching of antigenicity to a circulating strain.
Gregory, James A.; Topol, Aaron B.; Doerner, David Z.
Infectious diseases disproportionately affect indigent regions and are the greatest cause of childhood mortality in developing countries. Practical, low-cost vaccines for use in these countries are paramount to reducing disease burdens and concomitant poverty. Algae are a promising low-cost system for producing vaccines that can be orally delivered, thereby avoiding expensive purification and injectable delivery. We engineered the chloroplast of the eukaryotic alga Chlamydomonas reinhardtii to produce a chimeric protein consisting of the 25-kDa Plasmodium falciparum surface protein (Pfs25) fused to the β subunit of the cholera toxin (CtxB) to investigate an alga-based whole-cell oral vaccine. Pfs25 is a promising malaria transmission-blocking vaccine candidate that has been difficult to produce in traditional recombinant systems due to its structurally complex tandem repeats of epidermal growth factor-like domains. The noncatalytic CtxB domain of the cholera holotoxin assembles into a pentameric structure and acts as a mucosal adjuvant by binding GM1 ganglioside receptors on gut epithelial cells. We demonstrate that CtxB-Pfs25 accumulates as a soluble, properly folded and functional protein within algal chloroplasts, and it is stable in freeze-dried alga cells at ambient temperatures. In mice, oral vaccination using freeze-dried algae that produce CtxB-Pfs25 elicited CtxB-specific serum IgG antibodies and both CtxB- and Pfs25-specific secretory IgA antibodies. These data suggest that algae are a promising system for production and oral delivery of vaccine antigens, but as an orally delivered adjuvant, CtxB is best suited for eliciting secretory IgA antibodies for vaccine antigens against pathogens that invade mucosal surfaces using this strategy. PMID:23603678
S. Chimeno Zoth
Full Text Available Newcastle disease virus (NDV is the causative agent of an economically important disease, which affects all species of birds worldwide. Current vaccination programs for NDV include the use of either low-virulent live-virus vaccines or inactivated vaccines to induce protective immunity while producing minimal adverse effects in birds. In order to further characterize the immune response elicited by live virus and inactivated NDV conventional vaccines in chickens, we evaluated the presence of specific antibodies in different secretions and in tissue culture supernatants of immunized birds. To this end, we analyzed all the samples by ELISA, using an indirect assay set up in the laboratory. Specific anti-NDV IgG antibodies were detected in tracheal and cloacal swabs and tracheal and intestinal washes of immunized animals. We also found specific anti-NDV IgG antibodies in tracheal and intestinal tissue culture supernatants, indicating that the IgG found in swabs and washes was not transudated from serum or, at least, was not all transudated from serum. Knowledge about the mechanisms involved in the immune response of chickens to different NDV vaccines should increase our understanding of the mucosal response against the virus and, eventually, provide new useful information for the development and evaluation of synthetic vaccines.
Yusibov, Vidadi; Streatfield, Stephen J; Kushnir, Natasha
In the last few years, plants have become an increasingly attractive platform for recombinant protein production. This builds on two decades of research, starting with transgenic approaches to develop oral vaccines in which antigens or therapeutics can be delivered in processed plant biomass, and progressing to transient expression approaches whereby high yields of purified targets are administered parenterally. The advantages of plant-based expression systems include high scalability, low upstream costs, biocontainment, lack of human or animal pathogens, and ability to produce target proteins with desired structures and biological functions. Using transgenic and transient expression in whole plants or plant cell culture, a variety of recombinant subunit vaccine candidates, therapeutic proteins, including monoclonal antibodies, and dietary proteins have been produced. Some of these products have been tested in early phase clinical trials, and show safety and efficacy. Among those are mucosal vaccines for diarrheal diseases, hepatitis B and rabies; injectable vaccines for non-Hodgkin's lymphoma, H1N1 and H5N1 strains of influenza A virus, and Newcastle disease in poultry; and topical antibodies for the treatment of dental caries and HIV. As lead plant-based products have entered clinical trials, there has been increased emphasis on manufacturing under current Good Manufacturing Practice (cGMP) guidelines, and the preparation and presentation to the relevant government agencies of regulatory packages.
Andersen, Stig Henrik; Vervelde, Lonneke; Sutton, Kate
controls, one group was vaccinated intramuscularly twice with a commercial inactivated ND virus (NDV) vaccine, and the last group was vaccinated orally twice with a commercial live attenuated NDV vaccine. PBMC were ex vivo stimulated with ConA or with NDV antigen. The ICS assay was used to determine......The aim of this study was to optimise and evaluate an intracellular cytokine staining (ICS) assay for assessment of T cell IFN-γ responses in chickens vaccinated against Newcastle disease (ND). We aimed to validate currently available antibodies to chicken IFN-γ using transfected CHO cells......-γ responses, with significantly elevated levels of IFN-γ producing cells in the B19 chickens vaccinated orally with live attenuated NDV vaccine. This was not the case in the B21 animals, indicating a haplotype restricted variation. In contrast, the CD3+TCR1γδ−CD4+ (Th) population did not show a significant...
Coler, Rhea N; Hudson, Thomas; Hughes, Sean; Huang, Po-Wei D; Beebe, Elyse A; Orr, Mark T
The discovery of new vaccines against infectious diseases and cancer requires the development of novel adjuvants with well-defined activities. The TLR4 agonist adjuvant GLA-SE elicits robust Th1 responses to a variety of vaccine Ags and is in clinical development for both infectious diseases and cancer. We demonstrate that immunization with a recombinant protein Ag and GLA-SE also induces granzyme A expression in CD4 T cells and produces cytolytic cells that can be detected in vivo. Surprisingly, these in vivo CTLs were CD4 T cells, not CD8 T cells, and this cytolytic activity was not dependent on granzyme A/B or perforin. Unlike previously reported CD4 CTLs, the transcription factors Tbet and Eomes were not necessary for their development. CTL activity was also independent of the Fas ligand-Fas, TRAIL-DR5, and canonical death pathways, indicating a novel mechanism of CTL activity. Rather, the in vivo CD4 CTL activity induced by vaccination required T cell expression of CD154 (CD40L) and target cell expression of CD40. Thus, vaccination with a TLR4 agonist adjuvant induces CD4 CTLs, which kill through a previously unknown CD154-dependent mechanism. Copyright © 2015 by The American Association of Immunologists, Inc.
Matsui, Takeshi; Asao, Hiroshi; Ki, Misa; Sawada, Kazutoshi; Kato, Ko
Pig edema disease is a bacterial disease caused by Shiga toxin 2e-producing Escherichia coli belonging mainly to serotypes O138, O139, and O141. The B subunit of Shiga toxin 2e (Stx2eB) is a candidate protein for use in a vaccine against edema disease. We produced this protein in transgenic lettuce (Lactuca sativa), an edible plant that can be cultivated in a factory setting. In a transient expression system, we found that NtADH 5'-untranslated region (5'-UTR) functions as a translational enhancer in lettuce cells, and that Stx2eB accumulates most efficiently in the endoplasmic reticulum (ER) of lettuce cells. Stx2eB was produced in stable transgenic lettuce plants expressing a modified Stx2eB gene fused with the NtADH 5'-UTR and sequence encoding ER localization signals.
Full Text Available Three leptospiral bacterins, produced with different serovars of Serogroup Sejroe, namely the hardjo (bacterin A, wolffi (bacterin B and guaricura (bacterin C, were evaluated in male hamsters (Mesocricetus auratus by comparing the agglutinating and neutralizing antibodies titers using microscopic agglutination (MAT and in vitro growth inhibition (GIT tests. The immunization schedule was based on two 1.0 mL doses of non-diluted formalininactivated whole culture bacterin given through subcutaneous route with 10-day interval. The challenge was performed ten days after the second vaccine dose, when the animals were inoculated with 0.2 mL of non-inactivated cultures of each serovar through intraperitoneal route. On the 21st post-challenge day (PCD, all animals were bled and their sera were joined in pools (n=8 and tested by MAT and GIT. All vaccinated and control animals presented no clinical signs of leptospirosis after the challenge, but the serovar guaricura was isolated from the kidneys of control animals on the 21st PCD. The MAT results showed cross agglutinins between serovars hardjo and wolffi, and between wolffi and guaricura. The GIT results revealed the presence of cross neutralizing antibodies between serovars wolffi or guaricura against hardjo, wolffi and guaricura. It was found that the tested strain of serovar hardjo did not produce detectable levels of neutralizing antibodies, indicating its poor immunogenicity.
Stefan W Metz
Full Text Available The emerging arthritogenic, mosquito-borne chikungunya virus (CHIKV causes severe disease in humans and represents a serious public health threat in countries where Aedes spp mosquitoes are present. This study describes for the first time the successful production of CHIKV virus-like particles (VLPs in insect cells using recombinant baculoviruses. This well-established expression system is rapidly scalable to volumes required for epidemic responses and proved well suited for processing of CHIKV glycoproteins and production of enveloped VLPs. Herein we show that a single immunization with 1 µg of non-adjuvanted CHIKV VLPs induced high titer neutralizing antibody responses and provided complete protection against viraemia and joint inflammation upon challenge with the Réunion Island CHIKV strain in an adult wild-type mouse model of CHIKV disease. CHIKV VLPs produced in insect cells using recombinant baculoviruses thus represents as a new, safe, non-replicating and effective vaccine candidate against CHIKV infections.
Saluja, V.; Amorij, J-P.; Kapteyn, J. C.; de Boer, A. H.; Frijlink, H. W.; Hinrichs, W. L. J.
The aim of this study was to investigate two different processes to produce a stable influenza subunit vaccine powder for pulmonary immunization i.e. spray drying (SD) and spray freeze drying (SFD). The formulations were analyzed by proteolytic assay, single radial immunodiffusion assay (SRID),
Cloeckaert, Axel; Zygmunt, Michel S; Guilloteau, Laurence A
Brucella abortus RB51 is a rough (R) stable vaccine strain used in cattle and is believed to be devoid of O-side chain. We analyzed by use of a panel of monoclonal antibodies (MAbs) directed against seven previously defined O-polysaccharide (O-PS) epitopes the O-chain expression in strain RB51. Two MAbs specific for the C/Y (A=M) and C (M>A) epitopes showed low bindings in ELISA to strain RB51. O-chain expression was further confirmed by Western blot after SDS-PAGE of strain RB51. In particular, the MAb of C (M>A) specificity, showing preferential binding to M-dominant smooth (S) Brucella strains, revealed in strain RB51 a typical smooth-lipopolysaccharide (S-LPS) pattern which resembled that of M-dominant S-LPS. Thus, the results clearly show that strain RB51 produces low levels of M-like O-antigen.
Moyle, Peter Michael
Traditional vaccination approaches (e.g. live attenuated or killed microorganisms) are among the most effective means to prevent the spread of infectious diseases. These approaches, nevertheless, have failed to yield successful vaccines against many important pathogens. To overcome this problem, methods have been developed to identify microbial components, against which protective immune responses can be elicited. Subunit antigens identified by these approaches enable the production of defined vaccines, with improved safety profiles. However, they are generally poorly immunogenic, necessitating their administration with potent immunostimulatory adjuvants. Since few safe and effective adjuvants are currently used in vaccines approved for human use, with those available displaying poor potency, or an inability to stimulate the types of immune responses required for vaccines against specific diseases (e.g. cytotoxic lymphocytes (CTLs) to treat cancers), the development of new vaccines will be aided by the availability of characterized platforms of new adjuvants, improving our capacity to rationally select adjuvants for different applications. One such approach, involves the addition of microbial components (pathogen-associated molecular patterns; PAMPs), that can stimulate strong immune responses, into subunit vaccine formulations. The conjugation of PAMPs to subunit antigens provides a means to greatly increase vaccine potency, by targeting immunostimulation and antigen to the same antigen presenting cell. Thus, methods that enable the efficient, and inexpensive production of antigen-adjuvant fusions represent an exciting mean to improve immunity towards subunit antigens. Herein we review four protein-based adjuvants (flagellin, bacterial lipoproteins, the extra domain A of fibronectin (EDA), and heat shock proteins (Hsps)), which can be genetically fused to antigens to enable recombinant production of antigen-adjuvant fusion proteins, with a focus on their
Loucq, Christian; Birkett, Ashley; Poland, David; Botting, Carla; Nunes, Julia; Ethelston, Sally
With approximately 225 million new cases and 800,000 deaths annually, malaria exacts a tremendous toll--mostly on African children under the age of five. Late-stage trials of an advanced malaria vaccine candidate--which, if approved, would become the world's first malaria vaccine--are under way, and it may be ready for use by 2015. This article recounts the pivotal roles in that achievement played by collaborations of nonprofit organizations, pharmaceutical companies, private and public donors, and countries whose citizens would benefit most directly from a vaccine. Just as it takes a village to raise a child, it has taken a huge number of stakeholders around the world to reach this point. Developing even more effective vaccines for malaria and other diseases will require continued hard work and creative thinking from scientists, regulators, and policy makers.
... disease — reinforcing the importance of vaccines in your pet's preventive health care program. Are there risks? Any treatment carries some risk, but these risks should be weighed against the benefits of protecting your pet from potentially fatal diseases. ...
Full Text Available Andes virus (ANDV and ANDV-like viruses are responsible for most hantavirus pulmonary syndrome (HPS cases in South America. Recent studies in Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment for HPS. Unfortunately, availability of convalescent plasma from survivors of this lethal disease is very limited. We are interested in exploring the concept of using DNA vaccine technology to produce antiviral biologics, including polyclonal neutralizing antibodies for use in humans. Geese produce IgY and an alternatively spliced form, IgYΔFc, that can be purified at high concentrations from egg yolks. IgY lacks the properties of mammalian Fc that make antibodies produced in horses, sheep, and rabbits reactogenic in humans. Geese were vaccinated with an ANDV DNA vaccine encoding the virus envelope glycoproteins. All geese developed high-titer neutralizing antibodies after the second vaccination, and maintained high-levels of neutralizing antibodies as measured by a pseudovirion neutralization assay (PsVNA for over 1 year. A booster vaccination resulted in extraordinarily high levels of neutralizing antibodies (i.e., PsVNA80 titers >100,000. Analysis of IgY and IgYΔFc by epitope mapping show these antibodies to be highly reactive to specific amino acid sequences of ANDV envelope glycoproteins. We examined the protective efficacy of the goose-derived antibody in the hamster model of lethal HPS. α-ANDV immune sera, or IgY/IgYΔFc purified from eggs, were passively transferred to hamsters subcutaneously starting 5 days after an IM challenge with ANDV (25 LD50. Both immune sera, and egg-derived purified IgY/IgYΔFc, protected 8 of 8 and 7 of 8 hamsters, respectively. In contrast, all hamsters receiving IgY/IgYΔFc purified from normal geese (n=8, or no-treatment (n=8, developed lethal HPS. These findings demonstrate that the DNA vaccine/goose platform can be used to produce a candidate antiviral
Coler, Rhea N.; Hudson, Thomas; Hughes, Sean; Huang, Po-wei D.; Beebe, Elyse A.; Orr, Mark T.
The discovery of new vaccines against infectious diseases and cancer requires the development of novel adjuvants with well-defined activities. The TLR4 agonist adjuvant GLA-SE elicits robust TH1 responses to a variety of vaccine antigens and is in clinical development for both infectious diseases and cancer. We demonstrate that immunization with a recombinant protein antigen and GLA-SE also induces granzyme A expression in CD4 T cells and produces cytolytic cells that can be detected in vivo. Surprisingly these in vivo CTLs were CD4 T cells, not CD8 T cells and this cytolytic activity was not dependent on granzyme A/B or perforin. Unlike previously reported CD4 CTLs the transcription factors Tbet and Eomes were not necessary for their development. CTL activity was also independent of the FasL-Fas, TRAIL-DR5, and canonical death pathways, indicating a novel mechanism of CTL activity. Rather, the in vivo CD4 CTL activity induced by vaccination required T cell expression of CD154 (CD40 ligand) and target cell expression of CD40. Thus, vaccination with a TLR4 agonist adjuvant induces CD4 CTLs which kill through a previously unknown CD154-dependent mechanism. PMID:26297758
Glisser, Mario Boris; Barragán, Tatiana del Carmen; Weisstaub, Gerardo
To compare official breastfeeding (BF) data with those obtained by interviews conducted during regular vaccination visits. A pilot descriptive study with convenience sampling was conducted by interviewing guardians of children attending vaccination in four Primary Care Centres in south Santiago. BF prevalence indicators were calculated and stratified by age and education of mothers. A comparison was made between the results and the official ones reported by each Centre. Chi-squared (X2) was calculated to evaluate differences (P<.05) RESULTS: A total of 1990 cases were analysed, in which exclusive BF prevalence was 43.4%, 34.2% and 8.8%, at 2, 4, and 6 months, respectively. At the sixth month, official data (41%) was significantly higher (P<.001). Mothers with less than 12 years of schooling have a lower prevalence of exclusive BF at the 4th month than those with higher education (28.4% vs. 37.8%, respectively, P<.05). Even considering the small size of the sample studied, exclusive BF prevalence obtained is surprisingly lower than official reported data. That difference might be explained by: (a) children brought to vaccinations are roughly two fold the number brought to well-child clinics and, (b) potential bias in official data obtained by staff in charge of promotion and education on BF practices, which could distort the results. Further studies are needed to improve the methodology for collecting and analysis BF data. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.
Mikyšková, Romana; Indrová, Marie; Šímová, Jana; Bieblová, Jana; Bubeník, Jan; Reiniš, Milan
Roč. 25, č. 6 (2011), s. 1683-1689 ISSN 1021-335X R&D Projects: GA ČR GA301/09/1024; GA ČR GA301/07/1410 Grant - others:EK(XE) EU-FP6-NOE018933 Institutional research plan: CEZ:AV0Z50520514 Keywords : gemcitabine * human papilloma virus * interleukin 12 * lung metastases * cellular vaccine s * immunotherapy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.835, year: 2011
Cárdenas-Canales, Elsa M.; Wolfe, Lisa L.; Tripp. Daniel W.,; Rocke, Tonie E.; Abbott, Rachel C.; Miller, Michael W.
We confirmed safety and immunogenicity of mass-produced vaccine baits carrying an experimental, commercial-source plague vaccine (RCN-F1/V307) expressing Yersinia pestis V and F1 antigens. Forty-five juvenile black-tailed prairie dogs (Cynomys ludovicianus) were randomly divided into three treatment groups (n=15 animals/group). Animals in the first group received one standard-dose vaccine bait (5×107 plaque-forming units [pfu]; STD). The second group received a lower-dose bait (1×107 pfu; LOW). In the third group, five animals received two standard-dose baits and 10 were left untreated but in contact. Two vaccine-treated and one untreated prairie dogs died during the study, but laboratory analyses ruled out vaccine involvement. Overall, 17 of 33 (52%; 95% confidence interval for binomial proportion [bCI] 34−69%) prairie dogs receiving vaccine-laden bait showed a positive anti-V antibody response on at least one sampling occasion after bait consumption, and eight (24%; bCI 11–42%) showed sustained antibody responses. The STD and LOW groups did not differ (P≥0.78) in their proportions of overall or sustained antibody responses after vaccine bait consumption. Serum from one of the nine (11%; bCI 0.3–48%) surviving untreated, in-contact prairie dogs also had detectable antibody on one sampling occasion. We did not observe any adverse effects related to oral vaccination.
Cárdenas-Canales, Elsa M; Wolfe, Lisa L; Tripp, Daniel W; Rocke, Tonie E; Abbott, Rachel C; Miller, Michael W
We confirmed safety and immunogenicity of mass-produced vaccine baits carrying an experimental, commercial-source plague vaccine (RCN-F1/V307) expressing Yersinia pestis V and F1 antigens. Forty-five juvenile black-tailed prairie dogs ( Cynomys ludovicianus ) were randomly divided into three treatment groups (n=15 animals/group). Animals in the first group received one standard-dose vaccine bait (5×10(7) plaque-forming units [pfu]; STD). The second group received a lower-dose bait (1×10(7) pfu; LOW). In the third group, five animals received two standard-dose baits and 10 were left untreated but in contact. Two vaccine-treated and one untreated prairie dogs died during the study, but laboratory analyses ruled out vaccine involvement. Overall, 17 of 33 (52%; 95% confidence interval for binomial proportion [bCI] 34-69%) prairie dogs receiving vaccine-laden bait showed a positive anti-V antibody response on at least one sampling occasion after bait consumption, and eight (24%; bCI 11-42%) showed sustained antibody responses. The STD and LOW groups did not differ (P≥0.78) in their proportions of overall or sustained antibody responses after vaccine bait consumption. Serum from one of the nine (11%; bCI 0.3-48%) surviving untreated, in-contact prairie dogs also had detectable antibody on one sampling occasion. We did not observe any adverse effects related to oral vaccination.
allergy: • Vaccines produced in embryonated eggs, such as yellow fever vaccine, influenza vaccine and rabies vaccine. Yellow fever vaccine is most likely to contain significant amounts of egg protein. • Vaccines produced in chick fibroblast cell cultures, such as measles and measles-mumps-rubella (MMR) vaccines, do not.
Neves, Patrícia C. C.; Rudersdorf, Richard A.; Galler, Ricardo; Bonaldo, Myrna C.; de Santana, Marlon Gilsepp Veloso; Mudd, Philip A.; Martins, Maurício A.; Rakasz, Eva G.; Wilson, Nancy A.; Watkins, David I.
The yellow fever 17D (YF-17D) vaccine is one of the most efficacious vaccines developed to date. Interestingly, vaccination with YF-17D induces IFN-γ production early after vaccination (d 5–7) before the development of classical antigen-specific CD8+ and CD4+ T cell responses. Here we investigated the cellular source of this early IFN-γ production. At days 5 and 7 post vaccination activated CD8+ gamma-delta TCR T cells produced IFN-γ and TNF-α. Activated CD4+ T cells produced IFN-γ and TNF-α ...
Lagoutte, Priscillia; Mignon, Charlotte; Donnat, Stéphanie; Stadthagen, Gustavo; Mast, Jan; Sodoyer, Régis; Lugari, Adrien; Werle, Bettina
Virus-like particles (VLPs) are promising molecular structures for the design and construction of novel vaccines, diagnostic tools, and gene therapy vectors. Size, oligomer assembly and repetitiveness of epitopes are optimal features to induce strong immune responses. Several VLP-based vaccines are currently licensed and commercialized, and many vaccine candidates are now under preclinical and clinical studies. In recent years, the development of genetically engineered recombinant VLPs has accelerated the need for new, improved downstream processes. In particular, a rapid low cost purification process has been identified as a remaining key challenge in manufacturing process development. In the present study we set up a size-exclusion chromatography-based, scalable purification protocol for the purification of a VLP-based influenza A vaccine produced in Escherichia coli. Recombinant VLPs derived from the RNA bacteriophage MS2 displaying an epitope from the ectodomain of Matrix 2 protein from influenza A virus were produced and purified. The 3 steps purification protocol uses a recently developed multimodal size-exclusion chromatography medium (Capto™ Core 700) in combination with detergent extraction and size-exclusion polishing to reach a 89% VLP purity with a 19% yield. The combination of this downstream strategy following production in E. coli would be suited for production of VLP-based veterinary vaccines targeting livestock and companion animals where large amounts of doses must be produced at an affordable price. Copyright © 2016 Elsevier B.V. All rights reserved.
Kimura, Takayuki; Tse, Kevin; McArdle, Sara; Gerhardt, Teresa; Miller, Jacqueline; Mikulski, Zbigniew; Sidney, John; Sette, Alessandro; Wolf, Dennis; Ley, Klaus
Although immunization with major histocompatibility complex (MHC) class II-restricted apolipoprotein B (ApoB) peptides has been shown to be atheroprotective, the mechanism is unclear. Here, we investigated CD4+ T cell populations in immunized atherosclerotic mice. Peptides (16-mers) from mouse ApoB, the core protein of low-density lipoprotein (LDL), were screened for binding to I-Ab by computer prediction and confirmed by radiolabeled peptide competition. Three new peptides, P101 (FGKQGFFPDSVNKALY, 5.5 nM IC50), P102 (TLYALSHAVNSYFDVD, 6.8 nM), and P103 (LYYKEDKTSLSASAAS, 95 nM), were tested in an atherosclerosis model (Apoe-/- mice on Western diet). Immunization with each of the three peptides (1 time in complete Freund's adjuvant subcuntaneously and 4 time in incomplete Freund's adjuvant intraperitoneally) but not with adjuvant alone showed significantly reduced atherosclerotic plaques in the aortic root by serial sections and in the whole aorta by en face staining. There were no differences in body weight, LDL cholesterol, or triglycerides. Peritoneal leukocytes from ApoB peptide-immunized mice, but not control mice, secreted significant amounts of IL-10 (150 pg/ml). Flow cytometry showed that peptide immunization induced IL-10 in 10% of peritoneal CD4+ T cells, some of which also expressed chemokine (C-C motif) receptor 5 (CCR5). Vaccination with ApoB peptides expanded peritoneal FoxP3+ regulatory CD4+ T cells and more than tripled the number of CCR5+FoxP3+ cells. Similar trends were also seen in the draining mediastinal lymph nodes but not in the nondraining inguinal lymph nodes. We conclude that vaccination with MHC class II-restricted autologous ApoB peptides induces regulatory T cells (Tregs) and IL-10, suggesting a plausible mechanism for atheroprotection.NEW & NOTEWORTHY Vaccination against apolipoprotein B (ApoB), the protein of LDL, attracts attention as a novel approach to prevent atherosclerosis. We discovered major histocompatibility complex class II
Ulianova, O. V.; Uianov, S. S.; Li, Pengcheng; Luo, Qingming
A new method of photoinactivation of bacteria aimed at producing prototypes of vaccine preparations against extremely dangerous infections is described. The reactogenicity of the new prophylactic preparations was studied using the laser speckle contrast analysis (LASCA). The performed experimental studies show that bacterial suspensions, irradiated using different regimes of photoinactivation, do not cause detrimental effect on the blood microcirculation in laboratory animals.
Moreno, Javier; Vouldoukis, Ioannis; Schreiber, Paul; Martin, Virginie; McGahie, David; Gueguen, Sylvie; Cuisinier, Anne-Marie
Canine leishmaniasis, an important zoonotic disease of dogs, is the result of an ineffective and inappropriate immune response to infection with Leishmania infantum. It is widely accepted that the appropriate immune response is characterised by a T-helper (Th)1-dominated profile in an overall mixed Th1/Th2 response. The absence of a strong Th1 response is associated with progression to the clinical disease. Thus, there is a need for an effective vaccine that could modulate the immune response to a more appropriate profile against the parasite. In this study we measured the impact of the LiESP/QA-21 canine vaccine, recently launched commercially in Europe, on selected humoral and cellular immune markers for one year after a primary vaccination course. The humoral response to vaccination was characterised by a predominantly IgG2 profile. Vaccinated dogs developed long-lasting cell-mediated immune responses against L. infantum, specifically with a stronger ability of macrophages to reduce intracellular parasite burdens in co-culture with autologous lymphocytes compared to control dogs (p=0.0002), which was correlated with induction of inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO) derivatives. These results confirm that vaccination with LiESP/QA-21 is capable of inducing an appropriate Th1-dominated immune profile which persists for a full year. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
Kurokawa, M; Ishida, S; Asakawa, S; Iwasa, S
The amounts of endotoxin, histamine-sensitizing factor and lymphocytosis-promoting factor contained in combined diphtheria-pertussis-tetanus and combined diphteria-pertussis vaccines recently produced in Japan were determined and the relationships among them were statistically analyzed. The estimated values in histamine-sensitizing units (HSU) and lymphocytosispromoting units (LPU) per human dose ranged from 0.3 to 6 and from 0.4 to 5, respectively. A fairly wide range of endotoxin contents, which were expressed in body weight-decreasing units (BWDU), was also demonstrated. All the ranges were larger than those expected from experimental error. There was a positive correlation between the HSU and LPU values although the individual HSU-LPU ratios ranged from 0.3 to 3, but the range was markedly larger than the width of the 95% confidence interval of the mean ratio. Negative correlation between BWDU and LPU was also significant, probably because of the relatively large number degrees of freedom, though the coefficient was fairly small; while that between BWDU and HSU was not significant. The frequency distribution of individual values of HSU was divided into two lognormal distributions. With one of the two groups obtained by this subdivision, a distinct positive correlation bewteen HSU and LPU was demonstrated, but with the other group there was little correlation. Some differences between the two groups were also found in the correlations between BWDU and the other two variates. No factors responsible for the separation of the groups have yet been found.
Lee, D-H; Kwon, J-S; Lee, H-J; Lee, Y-N; Hur, W; Hong, Y-H; Lee, J-B; Park, S-Y; Choi, I-S; Song, C-S
The frequent economic losses incurred with H9N2 low pathogenic avian influenza viruses (LPAI) infection have raised serious concerns for the poultry industry. A 1-dose regimen with inactivated H9N2 LPAI vaccine could not prevent vaccinated poultry from becoming infected and from shedding wild viruses. A study was conducted to determine whether a 2-dose regimen of inactivated H9N2 LPAI vaccine could enhance the immunologic response in chickens. Such gel-primed and mineral oil-boosted regimen has produced encouraging results associated with improved immune responses to an H9N2 LPAI. This strategy could be cost effective and helpful for preventing avian influenza virus in the poultry industry.
Full Text Available Epidemics and outbreaks caused by infections of several subgenotypes of EV71 and other serotypes of coxsackie A viruses have raised serious public health concerns in the Asia-Pacific region. These concerns highlight the urgent need to develop a scalable manufacturing platform for producing an effective and sufficient quantity of vaccines against deadly enteroviruses. In this report, we present a platform for the large-scale production of a vaccine based on the inactivated EV71(E59-B4 virus. The viruses were produced in Vero cells in a 200 L bioreactor with serum-free medium, and the viral titer reached 10(7 TCID50/mL 10 days after infection when using an MOI of 10(-4. The EV71 virus particles were harvested and purified by sucrose density gradient centrifugation. Fractions containing viral particles were pooled based on ELISA and SDS-PAGE. TEM was used to characterize the morphologies of the viral particles. To evaluate the cross-protective efficacy of the EV71 vaccine, the pooled antigens were combined with squalene-based adjuvant (AddaVAX or aluminum phosphate (AlPO4 and tested in human SCARB2 transgenic (Tg mice. The Tg mice immunized with either the AddaVAX- or AlPO4-adjuvanted EV71 vaccine were fully protected from challenges by the subgenotype C2 and C4 viruses, and surviving animals did not show any degree of neurological paralysis symptoms or muscle damage. Vaccine treatments significantly reduced virus antigen presented in the central nervous system of Tg mice and alleviated the virus-associated inflammatory response. These results strongly suggest that this preparation results in an efficacious vaccine and that the microcarrier/bioreactor platform offers a superior alternative to the previously described roller-bottle system.
Riber, Ulla; Hansen, Mette Sif; Lauritsen, Klara Tølbøll
. hyosynoviae challenge inoculation three weeks later. Vaccination induced both antibodies and a cell-mediated immune response (CMI) in vaccinated pigs compared to placebo pigs as shown by M. hyosynoviae antigen (Ag) specific IFN-γ response in an IL-18 potentiated whole-blood IFN-γ stimulation assay (mean IFN...... placebo pigs the cytokine production before (day -1), and after (day 15) challenge inoculation was therefore further characterized by flow cytometry. Briefly, PBMC cultures were incubated with Ag, PBS or staphylococcus enterotoxin B (SEB) in the presence of recombinant porcine IL-18 (50 ng/ml). Cultured......-α were rare. However, CD4+ cells producing IFN-γ or TNF-α after Ag-stimulation were detected in vaccinated pigs, and increased IFN-γ level (iMFI) in cells co-producing IFN-γ and TNF-α was more pronounced in vaccinated pigs compared to placebo pigs in response to M. hyosynoviae challenge (day 15 p...
Mazurkova, N A; Desheva, Iu A; Shishkina, L N; Stavskiĭ, E A; Rudenko, L G
Study in CBA line mice of immunogenicity of cold adapted reassortant influenza virus H5N2 vaccine strain samples produced in rollers in MDCK and Vero cell cultures by using plant derived components. Antibody levels in blood sera and nasal swabs, lungs and small intestine of experimental vaccine strain sample immunized mice were evaluated by using HI reaction in accordance with WHO recommendations. Reassortant vaccine strain A/17/duck/Potsdam/86/92 (H5N2) produced in MDCK and Vero cells by using plant derived components (rice and soy flour hydrolyzate and plant protease based nutrient medium) after intranasal immunization of mice induced local and humoral antibodies, and the latter not only against homologous virus, but also against highly pathogenic avian influenza virus strains A/ Chicken/Suzdalka/Nov-11/2005 and A/Chicken/Kurgan/05/2005. Immunogenicity studies of reassortant influenza virus A/17/duck/Potsdam/86/92 (H5N2) vaccine strain samples cultivated in MDCK and Vero cells by using media with plant derived components in mice show high levels of humoral and secretory immunity.
Peng, Ying; Schoenlaub, Laura; Elliott, Alexandra; Mitchell, William; Zhang, Yan
To further understand the mechanisms of formalin-inactivated Coxiella burnetii phase I (PI) vaccine (PIV)-induced protection, we examined if B cell, T cell, CD4+ T cell, or CD8+ T cell deficiency in mice significantly affects the ability of PIV to confer protection against a C. burnetii infection. Interestingly, compared to wild-type (WT) mice, PIV conferred comparable levels of protection in CD4+ T cell- or CD8+ T cell-deficient mice and partial protection in T cell-deficient mice but did not provide measurable protection in B cell-deficient mice. These results suggest that PIV-induced protection depends on B cells. In addition, anti-PI-specific IgM was the major detectable antibody (Ab) in immune sera from PIV-vaccinated CD4+ T cell-deficient mice, and passive transfer of immune sera from PIV-vaccinated CD4+ T cell-deficient mice conferred significant protection. These results suggest that T cell-independent anti-PI-specific IgM may contribute to PIV-induced protection. Our results also suggested that PIV-induced protection may not depend on complement activation and Fc receptor-mediated effector functions. Furthermore, our results demonstrated that both IgM and IgG from PIV-vaccinated WT mouse sera were able to inhibit C. burnetii infection in vivo, but only IgM from PIV-vaccinated CD4+ T cell-deficient mouse sera inhibited C. burnetii infection. Collectively, these findings suggest that PIV-induced protection depends on B cells to produce protective IgM and IgG and that T cell-independent anti-PI-specific IgM may play a critical role in PIV-induced protection against C. burnetii infection. PMID:23545296
Lin, Chyongchiou J; Martin, Judith M; Cole, Kelly Stefano; Zimmerman, Richard K; Susick, Michael; Moehling, Krissy K; Levine, Min Z; Spencer, Sarah; Flannery, Brendan; Nowalk, Mary Patricia
Vitamin D is an immunomodulating hormone, which has been associated with susceptibility to infectious diseases. Serum vitamin D levels in 135 children ages 3-17 y were measured at baseline and hemagglutinin influenza antibody titers were measured pre- and 21 d post influenza vaccination with live attenuated influenza vaccine (LAIV) or inactivated influenza vaccine (IIV). Height and weight were derived from the electronic medical record and were used to calculate body mass index (BMI). Thirty-nine percent of children were ages 3-8 years; 75% were black, 34% were obese (BMI ≥ 95 th percentile); vitamin D levels were >20 ng/ml in 55%. In linear regression analyses, post vaccination antibody titers for LAIV B lineages (B Brisbane and B Massachusetts) were significantly higher among those with lower vitamin D levels and among younger participants (P vitamin D levels and responses to LAIV A strains (A/H1N1 and A/H3N2) or to any IIV strains or lineages were found. Low vitamin D levels were associated with higher response to LAIV B lineages in the 2014-2015 LAIV, but not related to LAIV A or any IIV strains.
Clarke, Jihong Liu; Paruch, Lisa; Dobrica, Mihaela-Olivia; Caras, Iuliana; Tucureanu, Catalin; Onu, Adrian; Ciulean, Sonya; Stavaru, Crina; Eerde, Andre; Wang, Yanliang; Steen, Hege; Haugslien, Sissel; Petrareanu, Catalina; Lazar, Catalin; Popescu, Costin-Ioan; Bock, Ralph; Dubuisson, Jean; Branza-Nichita, Norica
The hepatitis C virus (HCV) is a major etiologic agent for severe liver diseases (e.g. cirrhosis, fibrosis and hepatocellular carcinoma). Approximately 140 million people have chronic HCV infections and about 500 000 die yearly from HCV-related liver pathologies. To date, there is no licensed vaccine available to prevent HCV infection and production of a HCV vaccine remains a major challenge. Here, we report the successful production of the HCV E1E2 heterodimer, an important vaccine candidate, in an edible crop (lettuce, Lactuca sativa) using Agrobacterium-mediated transient expression technology. The wild-type dimer (E1E2) and a variant without an N-glycosylation site in the E2 polypeptide (E1E2∆N6) were expressed, and appropriate N-glycosylation pattern and functionality of the E1E2 dimers were demonstrated. The humoral immune response induced by the HCV proteins was investigated in mice following oral administration of lettuce antigens with or without previous intramuscular prime with the mammalian HEK293T cell-expressed HCV dimer. Immunization by oral feeding only resulted in development of weak serum levels of anti-HCV IgM for both antigens; however, the E1E2∆N6 proteins produced higher amounts of secretory IgA, suggesting improved immunogenic properties of the N-glycosylation mutant. The mice group receiving the intramuscular injection followed by two oral boosts with the lettuce E1E2 dimer developed a systemic but also a mucosal immune response, as demonstrated by the presence of anti-HCV secretory IgA in faeces extracts. In summary, our study demonstrates the feasibility of producing complex viral antigens in lettuce, using plant transient expression technology, with great potential for future low-cost oral vaccine development. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and the Association of Applied Biologists and John Wiley & Sons Ltd.
Le Mauff, François; Mercier, Geneviève; Chan, Philippe; Burel, Carole; Vaudry, David; Bardor, Muriel; Vézina, Louis-Philippe; Couture, Manon; Lerouge, Patrice; Landry, Nathalie
Influenza virus-like particles (VLPs) are noninfectious particles resembling the influenza virus representing a promising vaccine alternative to inactivated influenza virions as antigens. Medicago inc. has developed a plant-based VLP manufacturing platform allowing the large-scale production of GMP-grade influenza VLPs. In this article, we report on the biochemical compositions of these plant-based influenza candidate vaccines, more particularly the characterization of the N-glycan profiles of the viral haemagglutinins H1 and H5 proteins as well as the tobacco-derived lipid content and residual impurities. Mass spectrometry analyses showed that all N-glycosylation sites of the extracellular domain of the recombinant haemagglutinins carry plant-specific complex-type N-glycans having core α(1,3)-fucose, core β(1,2)-xylose epitopes and Lewis(a) extensions. Previous phases I and II clinical studies have demonstrated that no hypersensibility nor induction of IgG or IgE directed against these glycans was observed. In addition, this article showed that the plant-made influenza vaccines are highly pure VLPs preparations while detecting no protein contaminants coming either from Agrobacterium or from the enzymes used for the enzyme-assisted extraction process. In contrast, VLPs contain few host cell proteins and glucosylceramides associated with plant lipid rafts. Identification of such raft markers, together with the type of host cell impurity identified, confirmed that the mechanism of VLP formation in planta is similar to the natural process of influenza virus assembly in mammals. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.
... No vaccine produced in the United States contains penicillin. Egg protein is found in influenza and yellow ... bacteria. For children with a prior history of allergic reactions to any of these substances in vaccines, parents ...
Joanne M Lumsden
Full Text Available A phase 2a RTS,S/AS malaria vaccine trial, conducted previously at the Walter Reed Army Institute of Research, conferred sterile immunity against a primary challenge with infectious sporozoites in 40% of the 80 subjects enrolled in the study. The frequency of Plasmodium falciparum circumsporozoite protein (CSP-specific CD4(+ T cells was significantly higher in protected subjects as compared to non-protected subjects. Intrigued by these unique vaccine-related correlates of protection, in the present study we asked whether RTS,S also induced effector/effector memory (T(E/EM and/or central memory (T(CM CD4(+ T cells and whether one or both of these sub-populations is the primary source of cytokine production. We showed for the first time that PBMC from malaria-non-exposed RTS,S-immunized subjects contain both T(E/EM and T(CM cells that generate strong IL-2 responses following re-stimulation in vitro with CSP peptides. Moreover, both the frequencies and the total numbers of IL-2-producing CD4(+ T(E/EM cells and of CD4(+ T(CM cells from protected subjects were significantly higher than those from non-protected subjects. We also demonstrated for the first time that there is a strong association between the frequency of CSP peptide-reactive CD4(+ T cells producing IL-2 and the titers of CSP-specific antibodies in the same individual, suggesting that IL-2 may be acting as a growth factor for follicular Th cells and/or B cells. The frequencies of CSP peptide-reactive, TNF-α-producing CD4(+ T(E/EM cells and of CD4(+ T(E/EM cells secreting both IL-2 and TNF-α were also shown to be higher in protected vs. non-protected individuals. We have, therefore, demonstrated that in addition to TNF-α, IL-2 is also a significant contributing factor to RTS,S/AS vaccine induced immunity and that both T(E/EM and T(CM cells are major producers of IL-2.
A safety and feasibility study of an allogeneic colon cancer cell vaccine administered with a granulocyte-macrophage colony stimulating factor-producing bystander cell line in patients with metastatic colorectal cancer.
Zheng, Lei; Edil, Barish H; Soares, Kevin C; El-Shami, Khaled; Uram, Jennifer N; Judkins, Carol; Zhang, Zhe; Onners, Beth; Laheru, Daniel; Pardoll, Drew; Jaffee, Elizabeth M; Schulick, Richard D
Despite recent advances in earlier detection and improvements in chemotherapy, the 5-year survival rate of patients with metastatic colorectal carcinoma remains poor. Immunotherapy is a potentially effective therapeutic approach to the treatment of colorectal carcinoma. Preclinical studies have supported the antitumor activity of immunization with a granulocyte-macrophage colony-stimulating factor (GM-CSF) producing murine colon tumor cell vaccine. A novel colorectal cancer vaccine composed of irradiated, allogeneic human colon cancer cells and GM-CSF-producing bystander cells was developed and tested in combination with a single intravenous low dose of cyclophosphamide in a phase 1 study of patients with metastatic colorectal cancer. A total of nine patients were enrolled onto and treated in this study. Six patients had a history of colorectal adenocarcinoma hepatic metastases and underwent curative metastasectomy, while three other patients had unresectable stage IV disease. This study demonstrates the safety and feasibility of this vaccine administered in patients with metastatic colorectal cancer. At last follow-up, the six patients who underwent curative metastasectomy survived longer than 36 months, and four of these six patients were without disease recurrence. Immunologic correlate results suggest that the GM-CSF-producing colon cancer vaccine enhances the production of anti-MUC1 antibodies. This vaccine is feasible and safe. Future investigation of the efficacy and antitumor immunity of this vaccine is warranted.
Recently, a vaccine strain denominated T1/44 has been introduced to Ethiopia to prepare vaccines for field use. A total of 228 cattle were vaccinated with vaccines produced from this seed strain in three different zones of Ethiopia. Post - vaccinal reaction affected the vaccinated animals with over all attack rate of 1.02% (95% ...
R Mark Jones
Full Text Available Malaria transmission blocking vaccines (TBVs are considered an effective means to control and eventually eliminate malaria. The Pfs25 protein, expressed predominantly on the surface of the sexual and sporogonic stages of Plasmodium falciparum including gametes, zygotes and ookinetes, is one of the primary targets for TBV. It has been demonstrated that plants are an effective, highly scalable system for the production of recombinant proteins, including virus-like particles (VLPs. We engineered VLPs (Pfs25-CP VLP comprising Pfs25 fused to the Alfalfa mosaic virus coat protein (CP and produced these non-enveloped hybrid VLPs in Nicotiana benthamiana plants using a Tobacco mosaic virus-based 'launch' vector. Purified Pfs25-CP VLPs were highly consistent in size (19.3±2.4 nm in diameter with an estimated 20-30% incorporation of Pfs25 onto the VLP surface. Immunization of mice with one or two doses of Pfs25-CP VLPs plus Alhydrogel® induced serum antibodies with complete transmission blocking activity through the 6 month study period. These results support the evaluation of Pfs25-CP VLP as a potential TBV candidate and the feasibility of the 'launch' vector technology for the production of VLP-based recombinant vaccines against infectious diseases.
Vaccine - HPV; Immunization - HPV; Gardasil; HPV2; HPV4; Vaccine to prevent cervical cancer; Genital warts - HPV vaccine; Cervical dysplasia - HPV vaccine; Cervical cancer - HPV vaccine; Cancer of the cervix - HPV vaccine; Abnormal ...
Vacuna contra la fiebre hemorrágica argentina Candid#1 producida en la Argentina: Inmunogenicidad y seguridad Candid#1 vaccine against Argentine Hemorrhagic Fever produced in Argentina: Immunogenicity and safety
Delia A. Enria
Full Text Available Se realizó un estudio clínico en 946 voluntarios humanos sanos, donde se comparó la vacuna Candid#1 producida en Argentina con la elaborada en EE.UU., que había sido utilizada en estudios previos. Como objetivo primario se evaluó la equivalencia en la eficacia utilizando como marcador subrogante a la inmunogenicidad medida por detección de anticuerpos neutralizantes. Como objetivo secundario se evaluó la equivalencia en inocuidad comparando las tasas de reacciones adversas. Ambas vacunas mostraron una tasa equivalente de inmunogenicidad ligeramente superior al 95.5%, que es la eficacia estimada para Candid #1 en estudios previos. No se observaron eventos adversos graves relacionados con la vacuna. Los eventos adversos generales considerados relacionados fueron de escasa significación clínica y de resolución espontánea o con tratamiento sintomático; se presentaron en los receptores de ambas vacunas en tasas equivalentes (29.9% para la vacuna fabricada en la Argentina y 35.0% para la fabricada en EE.UU., e incluyeron: cefalea, decaimiento, mialgias, plaquetopenia leve (A clinical study in 946 human volunteers was done to compare Candid #1 vaccine manufactured in Argentina with the vaccine produced in USA that had been previously used. The efficacy was evaluated using immunogenicity measured by the detection of neutralizing antibodies as a subrogate marker. Safety was evaluated comparing the rate of adverse events. Both vaccines showed a comparable rate of seroconversion, slighty higher than the efficacy estimated from previous studies (95.5%. There were no severe adverse events related to the vaccines. The general events considered related to the vaccines were not clinically relevant and disappeared either spontaneously or with symptomatic treatment. Similar rates of adverse events (29.9% for the Argentine vaccine and 35.0% for the USA vaccine were found for both vaccines. These included: headache, weakness, myalgias, mild low blood
Smith, Michael J; Woods, Charles R; Marshall, Gary S
An increasing number of parents are questioning the safety and necessity of routine childhood immunizations. Locally produced vaccine risk communication materials may be effective in reassuring these parents. However, little is known about specific vaccine safety concerns in the state of Kentucky. An Internet-based survey focusing on parental vaccine safety concerns and potential vaccine risk communication strategies was sent to all members of the Kentucky Chapter of the Amerian Academy of Pediatrics. There were 121 respondents who routinely administered childhood vaccines. Of these, 85% reported parental concern about the combined measles-mumps-rubella (MMR) vaccine. Concerns about the influenza and human papillomavirus (HPV) vaccines were also frequent. Of the respondents, 46% noted parental skepticism about all vaccines in general. However, refusal of all vaccines was uncommon in most practices (median 1%, interquartile range 1%-3%). The belief that vaccines cause autism was the most prevalent parental concern, reported by 70% of pediatricians. Physicians also reported that a list of reliable vaccine information Websites and pamphlets addressing common vaccine safety concerns would be the most helpful materials to use during their discussions with concerned parents. These findings suggest that specific information about the MMR, influenza, and HPV vaccines, as well as data refuting the putative link between vaccines and autism would be useful to physicians who administer vaccinations. Respondents were especially interested in reliable vaccine information on the Internet. The Websites listed below offer accurate scientific information about vaccines and the diseases they prevent.
Martin, Virginie; Vouldoukis, Ioannis; Moreno, Javier; McGahie, David; Gueguen, Sylvie; Cuisinier, Anne-Marie
Control of canine leishmaniasis is an important objective for the benefit of dogs living in or visiting endemic areas and for public health because of the zoonotic nature of this disease. Resistance or susceptibility to developing canine leishmaniasis after exposure to Leishmania infantum is primarily determined by the ability of the immune system to develop an appropriate Th1-dominated specific response to the parasite. For this reason there is a need for effective canine vaccines that can decrease the number of dogs developing progressive infections. In this study, we followed the impact of the LiESP/QA-21 canine vaccine (composed of excreted-secreted proteins of L. infantum and the QA-21 saponin adjuvant), recently launched commercially in Europe, on selected humoral and cellular immune parameters following an infectious intravenous challenge with L. infantum promastigotes administered one year after the primary vaccine course. We also followed parasitological parameters to determine the parasitological status of the challenged dogs. In contrast to controls, vaccinated dogs retained significantly stronger cell-mediated immune responses against the parasite despite a virulent challenge and had significantly lower mean parasite burdens at the end of the study, associated with a lower probability of developing active infections. These results confirm that the immune responses generated by vaccination with LiESP/QA-21 are still effective against an intravenous challenge one year after the primary vaccine course.
Goodwin, Zakia I; Pascual, David W
Brucellosis is a livestock disease responsible for fetal loss due to abortions. Worldwide, this disease has profound economic and social impact by reducing the ability of livestock producers to provide an adequate supply of disease-free meat and dairy products. In addition to its presence in domesticated animals, brucellosis is harbored in a number of wildlife species creating new disease reservoirs, which adds to the difficulty of eradicating this disease. Broad and consistent use of the available vaccines would contribute in reducing the incidence of brucellosis. Unfortunately, this practice is not common. In addition, the current brucellosis vaccines cannot provide sterilizing immunity, and in certain circumstances, vaccinated livestock are not protected against co-mingling Brucella-infected wildlife. Given that these vaccines are inadequate for conferring complete protection for some vaccinated livestock, alternatives are being sought, and these include genetic modifications of current vaccines or their reformulations. Alternatively, many groups have sought to develop new vaccines. Subunit vaccines, delivered as a combination of soluble vaccine plus adjuvant or the heterologous expression of Brucella epitopes by different vaccine vectors are currently being tested. New live attenuated Brucella vaccines are also being developed and tested in their natural hosts. Yet, what is rarely considered is the route of vaccination which could improve vaccine efficacy. Since Brucella infections are mostly transmitted mucosally, mucosal delivery of a vaccine has the potential of eliciting a more robust protective immune response for improved efficacy. Hence, this review will examine these questions and provide the status of new vaccines for livestock brucellosis. Copyright Â© 2016 Elsevier B.V. All rights reserved.
This is a review of the progress made so far in the effort to produce a malaria vaccine. The problems that have made it impossible to get an effective vaccine for malaria are discussed. Also examined are the current efforts to produce the vaccine and the prospects for an effective vaccine in the future. Key words: Vaccine ...
Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by the ...
Dubé, Eve; Laberge, Caroline; Guay, Maryse; Bramadat, Paul; Roy, Réal; Bettinger, Julie A.
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
Dobrica, Mihaela-Olivia; Lazar, Catalin; Paruch, Lisa; Skomedal, Hanne; Steen, Hege; Haugslien, Sissel; Tucureanu, Catalin; Caras, Iuliana; Onu, Adrian; Ciulean, Sonya; Branzan, Alexandru; Clarke, Jihong Liu; Stavaru, Crina; Branza-Nichita, Norica
Chronic Hepatitis B Virus (HBV) infection leads to severe liver pathogenesis associated with significant morbidity and mortality. As no curable medication is yet available, vaccination remains the most cost-effective approach to limit HBV spreading and control the infection. Although safe and efficient, the standard vaccine based on production of the small (S) envelope protein in yeast fails to elicit an effective immune response in about 10% of vaccinated individuals, which are at risk of infection. One strategy to address this issue is the development of more immunogenic antigens. Here we describe a novel HBV antigen obtained by combining relevant immunogenic determinants of S and large (L) envelope proteins. Our approach was based on the insertion of residues 21-47 of the preS1 domain of the L protein (nomenclature according to genotype D), involved in virus attachment to hepatocytes, within the external antigenic loop of S. The resulting S/preS121-47 chimera was successfully produced in HEK293T and Nicotiana benthamiana plants, as a more economical recombinant protein production platform. Comparative biochemical, functional and electron microscopy analysis indicated assembly of the novel antigen into subviral particles in mammalian and plant cells. Importantly, these particles preserve both S- and preS1-specific epitopes and elicit significantly stronger humoral and cellular immune responses than the S protein, in both expression systems used. Our data promote this antigen as a promising vaccine candidate to overcome poor responsiveness to the conventional, S protein-based, HBV vaccine. Copyright © 2017 Elsevier B.V. All rights reserved.
Surveillance of adverse events after the first trivalent inactivated influenza vaccine produced in mammalian cell culture (Flucelvax(®)) reported to the Vaccine Adverse Event Reporting System (VAERS), United States, 2013-2015.
Moro, Pedro L; Winiecki, Scott; Lewis, Paige; Shimabukuro, Tom T; Cano, Maria
In November 2012, the first cell cultured influenza vaccine, a trivalent subunit inactivated influenza vaccine (Flucelvax(®), ccIIV3), was approved in the US for adults aged ≥ 18 years. To assess adverse events (AEs) after ccIIV3 reported to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. We searched VAERS for US reports after ccIIV3 among persons vaccinated from July 1, 2013-March 31, 2015. Medical records were requested for reports classified as serious (death, hospitalization, prolonged hospitalization, disability, life-threatening-illness), and those suggesting anaphylaxis and Guillain-Barré syndrome (GBS). Physicians reviewed available information and assigned a primary clinical category using MedDRA system organ classes (SOC) to each report. Empirical Bayesian data mining was used to identify disproportional AE reporting following ccIIV3. VAERS received 629 reports following ccIIV3 of which 313 were for administration of vaccine to persons reports with an AE documented, 19 (6.1%) were serious and the most common categories were 152 (49.2%) general disorders and administration site conditions (mostly injection site and systemic reactions) and 73 (23.6%) immune system disorders with two reports of anaphylaxis. Four reports of GBS were submitted. Disproportional reporting was identified for 'drug administered to patient of inappropriate age.' Review of VAERS reports did not identify any concerning pattern of AEs after ccIIV3. Injection site and systemic reactions were the most commonly reported AEs, similar to the pre-licensure clinical trials. Reports following ccIIV3 in persons <18 years highlight the need for education of healthcare providers regarding approved ccIIV3 use. Published by Elsevier Ltd.
Singh, Susheel K; Roeffen, Will; Mistarz, Ulrik H
BACKGROUND: The sexual stages of Plasmodium falciparum are responsible for the spread of the parasite in malaria endemic areas. The cysteine-rich Pfs48/45 protein, exposed on the surface of sexual stages, is one of the most advanced antigens for inclusion into a vaccine that will block transmission....... However, clinical Pfs48/45 sub-unit vaccine development has been hampered by the inability to produce high yields of recombinant protein as the native structure is required for the induction of functional transmission-blocking (TB) antibodies. We have investigated a downstream purification process...... or to facilitate protein purification, were evaluated at small scale. None of these modifications affected the overall yield of recombinant protein. Consequently, R0.6C with a C-terminal his tag was used for upstream and downstream process development. A simple work-flow was developed consisting of batch...
Singh, S.K; Roeffen, W.; Mistarz, U.H.; Chourasia, B.K.; Yang, F.; Rand, K.D.; Sauerwein, R.W.; Theisen, M.
BACKGROUND: The sexual stages of Plasmodium falciparum are responsible for the spread of the parasite in malaria endemic areas. The cysteine-rich Pfs48/45 protein, exposed on the surface of sexual stages, is one of the most advanced antigens for inclusion into a vaccine that will block transmission.
The number of Japanese oversea travelers has gradually increased year by year, however they usually pay less attention to the poor physical condition at the voyage place. Many oversea travelers caught vaccine preventable diseases in developing countries. The Vaccine Guideline for Oversea Travelers 2010 published by Japanese Society of Travel Health will be helpful for spreading the knowledge of travelers' vaccine and vaccine preventable diseases in developing countries. Many travelers' vaccines have not licensed in Japan. I hope these travelers' vaccines, such as typhoid vaccine, meningococcal vaccine, cholera vaccine and so on will be licensed in the near future.
Tekewe, Alemu; Fan, Yuanyuan; Tan, Emilyn; Middelberg, Anton P J; Lua, Linda H L
A high global burden of rotavirus disease and the unresolved challenges with the marketed rotavirus vaccines, particularly in the developing world, have ignited efforts to develop virus-like particle (VLP) vaccines for rotavirus. While rotavirus-like particles comprising multiple viral proteins can be difficult to process, modular VLPs presenting rotavirus antigenic modules are promising alternatives in reducing process complexity and cost. In this study, integrated molecular and bioprocess engineering approaches were used to simplify the production of modular murine polyomavirus capsomeres and VLPs presenting a rotavirus 18 kDa VP8* antigen. A single construct was generated for dual expression of non-tagged murine polyomavirus capsid protein VP1 and modular VP1 inserted with VP8*, for co-expression in Escherichia coli. Co-expressed proteins assembled into pentameric capsomeres in E. coli. A selective salting-out precipitation and a polishing size exclusion chromatography step allowed the recovery of stable modular capsomeres from cell lysates at high purity, and modular capsomeres were successfully translated into modular VLPs when assembled in vitro. Immunogenicity study in mice showed that modular capsomeres and VLPs induced high levels of VP8*-specific antibodies. Our results demonstrate that a multipronged synthetic biology approach combining molecular and bioprocess engineering enabled simple and low-cost production of highly immunogenic modular capsomeres and VLPs presenting conformational VP8* antigenic modules. This strategy potentially provides a cost-effective production route for modular capsomere and VLP vaccines against rotavirus, highly suitable to manufacturing economics for the developing world. Biotechnol. Bioeng. 2017;114: 397-406. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Ito Tsuchiya, F M; Rosas Vargas, M A; Zepeda Ortega, B; Río del Navarro, Blanca Estela; Sienra Monge, Juan José Luis
Vaccination is one of the medicine's achievements to control and/or eradicate certain infectious diseases. Vaccines contain antigenic doses derived from microorganisms and/or its toxins, besides they are composed of other substances such as aluminum, gelatin, egg proteins, mercury components (as thimerosal), and antibiotics; therefore, these substances can produce hypersensitivity reactions. The above-mentioned reactions can be evidenced with itch, edema, hives, asthmatic crisis, hypotension and even anaphylactic shock. Due to the importance of vaccination, especially in childhood, it is essential to know the benefits of vaccines, their impact in morbidity and mortality decrease of certain infected-contagious diseases, as well as the adverse effects and the allergic reactions to their application. As immunizations prevent natural infections, they might contribute to a free infectious environment that would allow atopic response. This paper reviews the allergic reactions to vaccines and their influence on the development of atopic disease.
... doctorMost kids have no problems with the polio vaccine. However, call your doctor if your child has any reaction after getting the vaccine. Call ... Tell the doctor when (day and time) your child received the vaccine. You also should file a Vaccine Adverse Event ...
Martínez-Vega, Ruth Aralí; Carrasquila, Gabriel; Luna, Expedito; Ramos-Castañeda, José
The vaccine against Dengue virus (DENV), Dengvaxia® (CYD), produced by Sanofi-Pasteur, has been registered by several national regulatory agencies; nevertheless, the performance and security of this vaccine have been challenged in a series of recent papers. In this work, we intend to contribute to the debate by analyzing the concept of an enhancing vaccine, presenting objections to the epidemiological model base of the concept and, likewise, presenting data that contradict that concept. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available Immunodeficient mice transplanted with human peripheral blood mononuclear cells (PBMCs are promising tools to evaluate human immune responses to vaccines. However, these mice usually develop severe graft-versus-host disease (GVHD, which makes estimation of antigen-specific IgG production after antigen immunization difficult. To evaluate antigen-specific IgG responses in PBMC-transplanted immunodeficient mice, we developed a novel NOD/Shi-scid-IL2rγnull (NOG mouse strain that systemically expresses the human IL-4 gene (NOG-hIL-4-Tg. After human PBMC transplantation, GVHD symptoms were significantly suppressed in NOG-hIL-4-Tg compared to conventional NOG mice. In kinetic analyses of human leukocytes, long-term engraftment of human T cells has been observed in peripheral blood of NOG-hIL-4-Tg, followed by dominant CD4+ T rather than CD8+ T cell proliferation. Furthermore, these CD4+ T cells shifted to type 2 helper (Th2 cells, resulting in long-term suppression of GVHD. Most of the human B cells detected in the transplanted mice had a plasmablast phenotype. Vaccination with HER2 multiple antigen peptide (CH401MAP or keyhole limpet hemocyanin (KLH successfully induced antigen-specific IgG production in PBMC-transplanted NOG-hIL-4-Tg. The HLA haplotype of donor PBMCs might not be relevant to the antibody secretion ability after immunization. These results suggest that the human PBMC-transplanted NOG-hIL-4-Tg mouse is an effective tool to evaluate the production of antigen-specific IgG antibodies.
Durham, L K; Longini, I M; Halloran, M E; Clemens, J D; Nizam, A; Rao, M
The authors present a nonparametric method for estimating vaccine efficacy as a smooth function of time from vaccine trials. Use of the method requires a minimum of assumptions. Estimation is based on the smoothed case hazard rate ratio comparing the vaccinated with the unvaccinated. The estimation procedure allows investigators to assess time-varying changes in vaccine-induced protection, such as those produced by waning and boosting. The authors use the method to reanalyze data from a vaccine trial of two cholera vaccines in rural Bangladesh. This analysis reveals the differential protection and waning effects for the vaccines as a function of biotype and age.
... list . Showing availability for 25,354 locations. Influenza Vaccine Recommended for everyone greater than or equal to ... which one may be right for you! Flu Vaccines Protects again influenza, commonly called flu, a respiratory ...
... are also common in babies with rotavirus.Before rotavirus vaccine, rotavirus disease was a common and serious health ... to 60 died. Since the introduction of the rotavirus vaccine, hospitalizations and emergency visits for rotavirus have dropped ...
Joung, Sun Myung; Ryoo, Sungweon
The anti-tuberculosis Bacille de Calmette et Guérin (BCG) vaccine was developed between 1905 and 1921 at Pasteur Institutes of Lille in France, and was adopted by many countries. BCG strains comprise natural mutants of major virulence factors of Mycobacterium tuberculosis and that BCG sub-strains differ markedly in virulence levels. The tuberculosis became endemic in Korea after the Korean War (1950s). The BCG strain, which was donated by Pasteur Institutes, was brought to Korea in 1955, and the first domestic BCG vaccine was produced by the National Defense Research Institute (NDRI), current Korea Centers for Disease Control and Prevention (KCDC), in 1960. Since 1987, BCG manufacture work was handed over to the Korean Institute of Tuberculosis (KIT), the freeze-dried BCG vaccine was manufactured at a scale required to meet the whole amount of domestic consumption. However, since 2006, the manufacture of BCG vaccine suspended and the whole amount of BCG was imported at this point of time. Now KIT is planning to re-produce the BCG vaccine in Korea under the supervision of KCDC, this will be render great role to National Tuberculosis Control Program (NTP) and provide initiating step for developing new tuberculosis vaccines in Korea.
Joung, Sun Myung
The anti-tuberculosis Bacille de Calmette et Guérin (BCG) vaccine was developed between 1905 and 1921 at Pasteur Institutes of Lille in France, and was adopted by many countries. BCG strains comprise natural mutants of major virulence factors of Mycobacterium tuberculosis and that BCG sub-strains differ markedly in virulence levels. The tuberculosis became endemic in Korea after the Korean War (1950s). The BCG strain, which was donated by Pasteur Institutes, was brought to Korea in 1955, and the first domestic BCG vaccine was produced by the National Defense Research Institute (NDRI), current Korea Centers for Disease Control and Prevention (KCDC), in 1960. Since 1987, BCG manufacture work was handed over to the Korean Institute of Tuberculosis (KIT), the freeze-dried BCG vaccine was manufactured at a scale required to meet the whole amount of domestic consumption. However, since 2006, the manufacture of BCG vaccine suspended and the whole amount of BCG was imported at this point of time. Now KIT is planning to re-produce the BCG vaccine in Korea under the supervision of KCDC, this will be render great role to National Tuberculosis Control Program (NTP) and provide initiating step for developing new tuberculosis vaccines in Korea. PMID:23858398
The search for ideal brucellosis vaccines remains active today. Currently, no licensed human or canine anti-brucellosis vaccines are available. In bovines, the most successful vaccine (S19) is only used in calves, as adult vaccination results in orchitis in male, prolonged infection, and possible abortion complications in pregnant female cattle. Another widely deployed vaccine (RB51) has a low protective efficacy. An ideal vaccine should exhibit a safe profile as well as enhance protective efficacy. However, currently available vaccines exhibit one or more major drawbacks. Smooth live attenuated vaccines suffer shortcomings such as residual virulence and serodiagnostic interference. Inactivated vaccines, in general, confer relatively low levels of protection. Recent developments to improve brucellosis vaccines include generation of knockout mutants by targeting genes involved in metabolism, virulence, and the lipopolysaccharide synthesis pathway, as well as generation of DNA vaccines, mucosal vaccines, and live vectored vaccines, have all produced varying degrees of success. Herein, we briefly review the bacteriology, pathogenesis, immunological implications, candidate vaccines, vaccinations, and models related to Brucella. PMID:28859268
Manini, Ilaria; Trombetta, Claudia Maria; Lazzeri, Giacomo; Pozzi, Teresa; Rossi, Stefania; Montomoli, Emanuele
Vaccination remains the principal way to control seasonal infections and is the most effective method of reducing influenza-associated morbidity and mortality. Since the 1940s, the main method of producing influenza vaccines has been an egg-based production process. However, in the event of a pandemic, this method has a significant limitation, as the time lag from strain isolation to final dose formulation and validation is six months. Indeed, production in eggs is a relatively slow process and production yields are both unpredictable and highly variable from strain to strain. In particular, if the next influenza pandemic were to arise from an avian influenza virus, and thus reduce the egg-laying hen population, there would be a shortage of embryonated eggs available for vaccine manufacturing. Although the production of egg-derived vaccines will continue, new technological developments have generated a cell-culture-based influenza vaccine and other more recent platforms, such as synthetic influenza vaccines.
Full Text Available Researches to develop vaccines with contraceptive effect are being carried out since the 1920s. Since 1972, the contraceptive vaccines are one of the priority programs of the World Health Organization (WHO Special Programme of Research, Development and Research Training in Human Reproduction. Rockefeller Foundation participates in implementing the program. Openly declared objective of creating such vaccines — the regulation of the population in the Third World countries. There are currently three main directions of contraceptive vaccine design: 1 vaccines targeted at blocking the production of gametes; 2 impairing their function; 3 violating the fertilization process. Contraceptive vaccines for more than 10 years are widely used to reduce fertility and castration of wild and domestic animals. In the commercial realization there are veterinary vaccines Equity®, Improvac®, GonaCon®, Repro-BLOC (based on gonadotropin-releasing hormone; SpayVac™ and IVT-PZP® (based on zona pellucida antigens. Clinical studies have shown effective contraceptive action (in women of vaccines, in which human chorionic gonadotropin is used as an antigen. At the same time, there are found the side effects of such vaccines: for vaccines containing gonadotropin-releasing hormone and luteinizing hormone as antigenic components — castration, impotence; for vaccines containing follicle stimulating hormone — oligospermia; zona pellucida antigens — irreversible oophoritis. This paper discusses approaches to detection of sterilizing components in vaccines intended for mass prevention of infectious diseases, not reported by manufacturers, and the consequences of their use. Hidden use of contraceptive vaccines, which already took place, can be detected: 1 by the presence of antibodies to their antigenic components (in unvaccinated by contraceptive vaccines people such antibodies do not exist, except infertility cases; 2 by change in the hormonal levels of the
Smith, D.J.; Forrest, S.; Ackley, D.H. [Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Computer Science; Perelson, A.S. [Los Alamos National Lab., NM (United States)
We performed computer simulations to study the effects of prior infection on vaccine efficacy. We injected three antigens sequentially. The first antigen, designated the prior, represented a prior infection or vaccination. The second antigen, the vaccine, represented a single component of the trivalent influenza vaccine. The third antigen, the epidemic, represented challenge by an epidemic strain. For a fixed vaccine to epidemic strain cross-reactivities to the vaccine and to the epidemic strains. We found that, for many cross-reactivities, vaccination, when it had been preceded by a prior infection, provided more protection than vaccination alone. However, at some cross-reactivities, the prior infection reduced protection by clearing the vaccine before it had the chance to produce protective memory. The cross-reactivities between the prior, vaccine and epidemic strains played a major role in determining vaccine efficacy. This work has applications to understanding vaccination against viruses such as influenza that are continually mutating.
People working on the CERN site who wish to be vaccinated may go to the Infirmary (ground-floor, bldg. 57), with their vaccine, without a prior appointment. The vaccine can be reimbursed directly by Uniqa providing you attach the receipt and the prescription that you will receive from the Medical Service the day of your injection at the infirmary. Ideally, the vaccination should take place between 1st October and 30th November 2007 (preferably between 14:00 and 16:00). CERN staff aged 50 or over are recommended to have influenza vaccinations. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and those convalescing from serious medical problems or after serious surgical operations. The Medical Service will not administer vaccines for family members or retired staff members, who must contact their normal family doctor. Medical Service
Lynch, Maureen; Bresee, Joseph S.; Gentsch, Jon R.; Glass, Roger I.
The past few years have seen important developments in understanding the epidemiological and virological characteristics of rotaviruses, and rapid progress has been made in rotavirus vaccine development, but further challenges remain before a vaccine is introduced into widespread use. The licensure of the first rotavirus vaccine, a tetravalent rhesus-based rotavirus vaccine, in the United States in 1998, marked a significant advance in preventing the morbidity associated with rotavirus diarrhea. The association between the tetravalent rhesus-based rotavirus vaccine and intussusception has created significant hurdles as well as new opportunities to study the pathogenesis of rotavirus and rotavirus vaccine infection. Several other rotavirus vaccine candidates are in late stages of development, and results from trials have been encouraging.
... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bovine Parainfluenza3 Vaccine. 113.309... Virus Vaccines § 113.309 Bovine Parainfluenza3 Vaccine. Bovine Parainfluenza3 Vaccine shall be produced... virus dose from the lot of Master Seed Virus shall be established as follows: (1) Twenty-five bovine...
Further, the possibilities of producing plant/edible vaccines, combination vaccines, and the recognition of the great value of the use of mucosal route for vaccination stand out as great promises for more viable animal health and husbandry worldwide. KEY WORDS: Vaccine research & development, Animal diseases ...
Chung, Eun Hee
Currently, the increasing numbers of vaccine administrations are associated with increased reports of adverse vaccine reactions. Whilst the general adverse reactions including allergic reactions caused by the vaccine itself or the vaccine components, are rare, they can in some circumstances be serious and even fatal. In accordance with many IgE-mediated reactions and immediate-type allergic reactions, the primary allergens are proteins. The proteins most often implicated in vaccine allergies are egg and gelatin, with perhaps rare reactions to yeast or latex. Numerous studies have demonstrated that the injectable influenza vaccine can be safely administered, although with appropriate precautions, to patients with severe egg allergy, as the current influenza vaccines contain small trace amounts of egg protein. If an allergy is suspected, an accurate examination followed by algorithms is vital for correct diagnosis, treatment and decision regarding re-vaccination in patients with immediate-type reactions to vaccines. Facilities and health care professionals should be available to treat immediate hypersensitivity reactions (anaphylaxis) in all settings where vaccines are administered.
L.A. Reperant (Leslie); G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert)
textabstractInfluenza virus infections yearly cause high morbidity and mortality burdens in humans, and the development of a new influenza pandemic continues to threaten mankind as a Damoclean sword. Influenza vaccines have been produced by using egg-based virus growth and passaging techniques that
The Frederick National Laboratory for Cancer Research’s Vaccine Pilot Plant, part of the Vaccine Clinical Materials Program (VCMP), is helping researchers produce investigational Zika vaccines for a new round of clinical trials. The plant has been
Clinical trial to evaluate safety and immunogenicity of an oral inactivated enterotoxigenic Escherichia coli prototype vaccine containing CFA/I overexpressing bacteria and recombinantly produced LTB/CTB hybrid protein.
Lundgren, A; Leach, S; Tobias, J; Carlin, N; Gustafsson, B; Jertborn, M; Bourgeois, L; Walker, R; Holmgren, J; Svennerholm, A-M
We have developed a new oral vaccine against enterotoxigenic Escherichia coli (ETEC) diarrhea containing killed recombinant E. coli bacteria expressing increased levels of ETEC colonization factors (CFs) and a recombinant protein (LCTBA), i.e. a hybrid between the binding subunits of E. coli heat labile toxin (LTB) and cholera toxin (CTB). We describe a randomized, comparator controlled, double-blind phase I trial in 60 adult Swedish volunteers of a prototype of this vaccine. The safety and immunogenicity of the prototype vaccine, containing LCTBA and an E. coli strain overexpressing the colonization factor CFA/I, was compared to a previously developed oral ETEC vaccine, consisting of CTB and inactivated wild type ETEC bacteria expressing CFA/I (reference vaccine). Groups of volunteers were given two oral doses of either the prototype or the reference vaccine; the prototype vaccine was administered at the same or a fourfold higher dosage than the reference vaccine. The prototype vaccine was found to be safe and equally well-tolerated as the reference vaccine at either dosage tested. The prototype vaccine induced mucosal IgA (fecal secretory IgA and intestine-derived IgA antibody secreting cell) responses to both LTB and CFA/I, as well as serum IgA and IgG antibody responses to LTB. Immunization with LCTBA resulted in about twofold higher mucosal and systemic IgA responses against LTB than a comparable dose of CTB. The higher dose of the prototype vaccine induced significantly higher fecal and systemic IgA responses to LTB and fecal IgA responses to CFA/I than the reference vaccine. These results demonstrate that CF over-expression and inclusion of the LCTBA hybrid protein in an oral inactivated ETEC vaccine does not change the safety profile when compared to a previous generation of such a vaccine and that the prototype vaccine induces significant dose dependent mucosal immune responses against CFA/I and LTB. Copyright © 2013 Elsevier Ltd. All rights reserved.
People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service
CERN Medical Service
People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor.CERN Medical Service
People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical service
People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service
... influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should NOT be ... What is live, attenuated influenza vaccine-LAIV (nasal spray)?A dose of flu vaccine is recommended every flu season. Children younger ...
Bluetongue virus (BTV) lacking functional NS3/NS3a protein is named Disabled Infectious Single Animal (DISA) vaccine. The BT DISA vaccine platform is broadly applied by exchange of serotype specific proteins. BT DISA vaccines are produced in standard cell lines in established production facilities, ...
... to any patient (or to the parent or legal representative in the case of a child) receiving vaccines... designed to treat diseases. Vaccines are designed to prevent diseases, by producing immunity. A child who is immune to a disease will not get sick from it. Immunity from Disease: Before vaccines, a child had...
Tennant, Sharon M.; Levine, Myron M.
Salmonella enterica serovar Typhi produces significant morbidity and mortality worldwide despite the fact that there are licensed S. Typhi vaccines available. This is primarily due to the fact that these vaccines are not used in the countries that most need them. There is growing recognition that an effective invasive Salmonella vaccine formulation must also prevent infection due to other Salmonella serovars. We anticipate that a multivalent vaccine that targets the following serovars will be needed to control invasive Salmonella infections worldwide: S. Typhi, S. Paratyphi A, S. Paratyphi B (currently uncommon but may become dominant again), S. Typhimurium, S. Enteritidis and S. Choleraesuis (as well as other Group C Salmonella). Live attenuated vaccines are an attractive vaccine formulation for use in developing as well as developed countries. Here, we describe the methods of attenuation that have been used to date to create live attenuated Salmonella vaccines and provide an update on the progress that has been made on these vaccines. PMID:25902362
Leila Roozbeh Nasiraie
Full Text Available Background: During the last two decades, significant advances have been made in the fields of lactococcal genetics and protein expression. Lactococcus lactis (L. lactis is an effective vector for protein expression and can be used as an antigen delivery system. Hence, L. lactis is an ideal candidate for mucosal immunotherapy. Profilin (Che a 2, the major allergen in Chenopodium album, is one of the most important causes of allergic diseases in desert and semi-desert areas, especially in Iran, Saudi Arabia, and Kuwait that was cloned and expressed in L. lactis for the first time. Methods: To construct L. lactis that expressed Che a 2, a DNA sequence was cloned and used to transform bacteria. Expression of Che a 2 was analyzed via monitoring of related RNA and protein. Hydrophobicity, adherence to HT-29 cells, antibiotic resistance, resistance to gastrointestinal contents, pH, and bile salt in recombinant and native L. lactis were evaluated. Results: Immunoblot analyses demonstrated that recombinant Che a 2 is expressed as a 32 kDa dimeric protein immunological studies showed it can bind human IgE. Both native and recombinant bacteria were sensitive to low pH and simulated gastric conditions. Bacterial survival was reduced 80-100% after 2 h of exposure to pH 1.5-2. Both native and recombinant bacteria were able to grow in 0.3 and 2% bile salts. After incubation of recombinant L. lactis in simulated gastric and intestinal juices for one and two hours, respectively, cell survival was reduced by 100%. Adhesion capability in both strains was minimal and there were no significant differences in any of our tests between native and recombinant bacteria. Conclusion: Successfully recombinant L. lactis with capability of expression Che a 2 was produced and revealed it is sensitive to gastrointestinal contents.
According to the IFAH, veterinary vaccines currently account for 26% of the global market in veterinary medicines, reflecting the importance of vaccines in animal health, as well as the number of wild and domesticated target species, and the monospecific nature of most vaccines. Multispecies vaccines include tetanus and rabies. In 2010, the number of food-producing animals was estimated to be roughly 20 billion and is rising gradually. Fowl currently represent the main food species. Veterinary vaccination has allowed the eradication of rinderpest, as officially declared last year (2011), jointly by the World Organisation for Animal Health (OIE) and the Food and Agriculture Organisation of the United Nations (FAO). Rinderpest was a real scourge, and was only the second viral disease to be totally eradicated (after human smallpox). One characteristic of veterinary vaccination is the DIVA approach, "differentiating infected from vaccinated animals". The DIVA strategy is especially interesting for regulated control of diseases like foot-and-mouth disease, infectious bovine rhinotracheitis, pseudorabies, and classical swine fever. DIVA vaccination requires prior serological testing. Vaccination is also used for wild animals such as foxes (rabies) and wild boars (classical swine fever). "In ovo" vaccination of fowl on day 18 of the incubation period is used to prevent Marek's disease for instance, and double vaccination (vector and insert) to prevent both Marek's disease and Gumboro's disease in fowl. Animal vaccination can also help to protect human health, as illustrated by fowl vaccination against salmonellosis.
Heegaard, Peter M. H.; Boas, Ulrik; Sørensen, Nanna Skall
for efficient immunostimulating compounds (adjuvants) that can increase the efficiency of vaccines, as dendrimers can provide molecularly defined multivalent scaffolds to produce highly defined conjugates with small molecule immunostimulators and/or antigens. The review gives an overview on the use...... of dendrimers as molecularly defined carriers/presenters of small antigens, including constructs that have built-in immunostimulatory (adjuvant) properties, and as stand-alone adjuvants that can be mixed with antigens to provide efficient vaccine formulations. These approaches allow the preparation...... of molecularly defined vaccines with highly predictable and specific properties and enable knowledge-based vaccine design substituting the traditional empirically based approaches for vaccine development and production....
Kaddar, Miloud; Milstien, Julie; Schmitt, Sarah
Brazil, the Russian Federation, India, China and South Africa--the countries known as BRICS--have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector's price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS' accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes.
Guarino, Cassandra; Asbie, Sanda; Rohde, Jennifer; Glaser, Amy; Wagner, Bettina
Borrelia burgdorferi can induce Lyme disease. Approved Lyme vaccines for horses are currently not available. In an effort to protect horses, veterinarians are using Lyme vaccines licensed for dogs. However, data to assess the response of horses to, or determine the efficacy of this off-label vaccine use are missing. Here, antibodies against outer surface protein A (OspA), OspC, and OspF were quantified in diagnostic serum submissions from horses with a history of vaccination with canine Lyme vaccines. The results suggested that many horses respond with low and often short-lasting antibody responses. Subsequently, four experimental vaccination trials were performed. First, we investigated antibody responses to three canine vaccines in B. burgdorferi-naïve horses. One killed bacterin vaccine induced antibodies against OspC. OspA antibodies were low for all three vaccines and lasted less than 16weeks. The second trial tested the impact of the vaccine dose using the OspA/OspC inducing bacterin vaccine in horses. A 2mL dose produced higher OspA and OspC antibody values than a 1mL dose. However, the antibody response again quickly declined, independent of dose. Third, the horses were vaccinated with 2 doses of a recombinant OspA vaccine. Previous vaccination and/or environmental exposure enhanced the magnitude and longevity of the OspA antibody response to about 20weeks. Last, the influence of intramuscular versus subcutaneous vaccine administration was investigated for the recombinant OspA vaccine. OspA antibody responses were not influenced by injection route. The current work highlights that commercial Lyme vaccines for dogs induce only transient antibody responses in horses which can also be of low magnitude. Protection from infection with B. burgdorferi should not be automatically assumed after vaccinating horses with Lyme vaccines for dogs. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
... foreign. Most preventive vaccines, including those aimed at cancer-causing viruses ( hepatitis B virus and human papillomavirus ), stimulate the ... 9 through 25 for the prevention of cervical cancer caused by HPV. Hepatitis B virus (HBV) vaccines. Chronic HBV infection can lead to ...
Tran, Vanessa; Liu, Jun; Behr, Marcel A
BCG is the collective name for a family of live attenuated strains of Mycobacterium bovis that are currently used as the only vaccine against tuberculosis (TB). There are two major reasons for studying the genome of these organisms: (i) Because they are attenuated, BCG vaccines provide a window into Mycobacterium tuberculosis virulence, and (ii) because they have provided protection in several clinical trials and case-control studies, BCG vaccines may shed light on properties required of a TB vaccine. Since the determination of the M. tuberculosis genome in 1998, the study of BCG vaccines has accelerated dramatically, offering data on the genomic differences between virulent M. tuberculosis, M. bovis, and the vaccine strains. While these findings have been rewarding for the study of virulence, there is unfortunately less accrued knowledge about protection. In this chapter, we review briefly the history of BCG vaccines and then touch upon studies over the past two decades that help explain how BCG underwent attenuation, concluding with some more speculative comments as to how these vaccines might offer protection against TB.
Angela S Clem
Full Text Available From a literature review of the current literature, this article provides an introduction to vaccine immunology including a primer on the components of the immune system, passive vs. active immunization, the mechanism(s by which immunizations stimulate(s immunity, and the types of vaccines available. Both the innate and adaptive immune subsystems are necessary to provide an effective immune response to an immunization. Further, effective immunizations must induce long-term stimulation of both the humoral and cell-mediated arms of the adaptive system by the production of effector cells and memory cells. At least seven different types of vaccines are currently in use or in development that produce this effective immunity and have contributed greatly to the prevention of infectious disease around the world.
Aline Lopes Lacerda
Full Text Available O artigo discute o uso de imagens como fonte de pesquisa para a história da medicina e da saúde pública, a partir da análise de um conjunto de fotografias sobre a produção da vacina contra a febre amarela, pertencente ao arquivo histórico da Fundação Rockefeller, depositado no Departamento de Arquivo e Documentação da Casa de Oswaldo Cruz/Fiocruz. Este arquivo foi produzido entre as décadas de 1930 e 1940 pelas instituições responsáveis pelos trabalhos de pesquisa e combate da doença no Brasil - a Fundação Rockefeller e o Serviço Nacional de Febre Amarela. Levantamos questões gerais recorrentes aos que utilizam imagens como fonte e/ou objeto de interpretação para a produção de conhecimento histórico, indicando os pontos de caráter teórico, conceitual e metodológico que envolvem esse processo para analisar imagens do conjunto arquivístico. A seguir, interpretamos as fotografias dos primórdios da produção da vacina antiamarílica.Through analysis of a set of photographs on the production of a yellow fever vaccine in Brazil, the article discusses the use of images as a research source in the history of medicine and public health. Part of a historical archive belonging to the Fundação Rockefeller, stored at the Casa de Oswaldo Cruz/Fiocruz, the photographs were produced between the 1930s and 1940s by the Fundação Rockefeller and Brazil's National Yellow Fever Service, institutions then responsible for research and control of the disease in Brazil. The article raises some questions generally posed by those who employ images as sources or objects of interpretation in the production of historical knowledge, and also points to the theoretical, conceptual, and methodological aspects involved in this process of analyzing images. It goes on to interpret these photographs from the beginnings of the yellow fever vaccine.
Nabel, Gary J
Traditional methods of vaccine development have not produced effective vaccines for several prevalent infectious diseases, including AIDS, malaria and tuberculosis. These difficult diseases call attention to the importance of new approaches that profit from modern technologies. Successful efforts in the past have typically taken advantage of naturally occurring, protective immune responses, but this avenue is not readily available in certain cases, such as in HIV infection, where the immune system rarely confers protective immunity. However, there are alternative strategies and areas of research that may facilitate the development of highly effective vaccines. These include the identification of immunogens that elicit broadly neutralizing antibodies, determination of the molecular and cellular basis for immune responses to the components of the infectious agent, the identification of relevant forms of viral proteins for antigen presentation, stimulation of relevant T-cell types, and enhancement of antigen-presenting, dendritic cell function. Answering these basic research questions will aid in rational vaccine design. It is also extremely important to optimize techniques for the testing and production of new vaccines including the quantitation of immune responses in animals and in humans, identification of surrogate markers of immune protection, streamlined vaccine production, and rapid evaluation of candidate vaccines for testing in clinical trials. We have put these ideas into practice in two recent studies in which we generated enhanced cytotoxic T lymphocyte (CTL) responses, while retaining robust humoral responses, to wild-type viral proteins by immunizing mice with genetically modified forms of HIV-1 Env, Gag and Pol delivered in the form of plasmid DNA expression vectors.
Skov, J.; Chettri, J. K.; Jaafar, R. M.
Two candidate adjuvants were tested with a commercial ERM dip vaccine (AquaVac™ Relera, MSD Animal Health) for rainbow trout in an experimental design compatible with common vaccination practices at farm level, i.e. immersion of fish in vaccine (±adjuvant) for 30 s. The adjuvants were...... the commercial product Montanide™ IMS 1312 VG PR (SEPPIC), and a soluble and ≥98% pure β-glucan from yeast (Saccharomyces cerevisiae) (Sigma-Aldrich). Hence, five experimental groups in duplicate were established and exposed to vaccine and adjuvants in the following combinations: AquaVac™ Relera (alone); Aqua......Vac™ Relera + Montanide™; AquaVac™ Relera + β-glucan; Montanide™ (alone); and β-glucan (alone). Approximately 450 degree days post-vaccination, the fish were bath-challenged with live Yersinia ruckeri to produce survival curves. Blood, skin and gills were sampled at selected time points during the course...
David AG Skibinski
Full Text Available The combination of diphtheria, tetanus, and pertussis vaccines into a single product has been central to the protection of the pediatric population over the past 50 years. The addition of inactivated polio, Haemophilus influenzae, and hepatitis B vaccines into the combination has facilitated the introduction of these vaccines into recommended immunization schedules by reducing the number of injections required and has therefore increased immunization compliance. However, the development of these combinations encountered numerous challenges, including the reduced response to Haemophilus influenzae vaccine when given in combination; the need to consolidate the differences in the immunization schedule (hepatitis B; and the need to improve the safety profile of the diphtheria, tetanus, and pertussis combination. Here, we review these challenges and also discuss future prospects for combination vaccines.
Full Text Available Decision-makers may consider vaccinating girls and boys with different HPV vaccines to benefit from their respective strengths; the quadrivalent (HPV4 prevents anogenital warts (AGW whilst the bivalent (HPV2 may confer greater cross-protection. We compared, to a girls-only vaccination program with HPV4, the impact of vaccinating: 1 both genders with HPV4, and 2 boys with HPV4 and girls with HPV2.We used an individual-based transmission-dynamic model of heterosexual HPV infection and diseases. Our base-case scenario assumed lifelong efficacy of 100% against vaccine types, and 46,29,8,18,6% and 77,43,79,8,0% efficacy against HPV-31,-33,-45,-52,-58 for HPV4 and HPV2, respectively.Assuming 70% vaccination coverage and lifelong cross-protection, vaccinating boys has little additional benefit on AGW prevention, irrespective of the vaccine used for girls. Furthermore, using HPV4 for boys and HPV2 for girls produces greater incremental reductions in SCC incidence than using HPV4 for both genders (12 vs 7 percentage points. At 50% vaccination coverage, vaccinating boys produces incremental reductions in AGW of 17 percentage points if both genders are vaccinated with HPV4, but increases female incidence by 16 percentage points if girls are switched to HPV2 (heterosexual male incidence is incrementally reduced by 24 percentage points in both scenarios. Higher incremental reductions in SCC incidence are predicted when vaccinating boys with HPV4 and girls with HPV2 versus vaccinating both genders with HPV4 (16 vs 12 percentage points. Results are sensitive to vaccination coverage and the relative duration of protection of the vaccines.Vaccinating girls with HPV2 and boys with HPV4 can optimize SCC prevention if HPV2 has higher/longer cross-protection, but can increase AGW incidence if vaccination coverage is low among boys.
Dalva Assunção Portari Mancini
Full Text Available The immunogenicity of the bivalent equine influenza vaccines (types A/Eq1 and A/Eq2 plain, or adjuvanted with aluminum hydroxide, produced at the Instituto Butantan, São Paulo, Brazil, was evaluated on horses sera taken before and after immunization by haemagglutination-inhibition (HI and single radial haemolysis (SRH tests. Seroconversion curves were established through weekly evaluations demonstrating good immunogenicity of both vaccines. Better humoral antibody titers were obtained with adjuvanted vaccine compared with the plain one, as showed by both methods used
... Educators Search English Español Your Child's Immunizations: Meningococcal Vaccines KidsHealth / For Parents / Your Child's Immunizations: Meningococcal Vaccines Print The meningococcal vaccines protect ...
Schiller, John T; Müller, Martin
The two licensed bivalent and quadrivalent human papillomavirus (HPV) L1 (the major papillomavirus virion protein) virus-like particle (VLP) vaccines are regarded as safe, effective, and well established prophylactic vaccines. However, they have some inherent limitations, including a fairly high production and delivery cost, virus-type restricted protection, and no reported therapeutic activity, which might be addressed with the development of alternative dosing schedules and vaccine products. A change from a three-dose to a two-dose protocol for the licensed HPV vaccines, especially in younger adolescents (aged 9-13 years), is underway in several countries and is likely to become the future norm. Preliminary evidence suggests that recipients of HPV vaccines might derive prophylactic benefits from one dose of the bivalent vaccine. Substantial interest exists in both the academic and industrial sectors in the development of second-generation L1 VLP vaccines in terms of cost reduction-eg, by production in Escherichia coli or alternative types of yeast. However, Merck's nonavalent vaccine, produced via the Saccharomyces cerevisiae production system that is also used for their quadrivalent vaccine, is the first second-generation HPV VLP vaccine to be available on the market. By contrast, other pharmaceutical companies are developing microbial vectors that deliver L1 genes. These two approaches would add an HPV component to existing live attenuated vaccines for measles and typhoid fever. Prophylactic vaccines that are based on induction of broadly cross-neutralising antibodies to L2, the minor HPV capsid protein, are also being developed both as simple monomeric fusion proteins and as virus-like display vaccines. The strong interest in developing the next generation of vaccines, particularly by manufacturers in middle-to-high income countries, increases the likelihood that vaccine production will become decentralised with the hope that effective HPV vaccines will be
Batson, A; Evans, P; Milstien, J B
Immunization programmes, having made significant progress in protecting over 80% of the world's children against six vaccine-preventable diseases, are now facing a crisis in funding for their vaccine supply. Contributing to this situation are changing donor priorities, rising prices, increased needs for vaccines. The Task Force on Situation Analysis for Vaccine Supply (TFSA) of the Children's Vaccine Initiative (CVI) has developed a framework which provides a logical division of countries into groups that might share similar vaccine supply systems. This framework provides a basis on which to analyse the needs and potential solutions for vaccine supply in countries based on their populations, national wealth, and current ability to produce vaccine. This framework has facilitated the development of strategies to strengthen national vaccine supply systems. It has also provided guidance for governments, donors and development agencies on the most appropriate actions for assuring the objective of sustainable vaccine supply.
Ajay Kumar Rai
Full Text Available Aim: To compare the newly formulated enterotoxaemia vaccine having oil and alum adjuvants, with presently available toxoid and alum precipitated vaccines. Materials and Methods: Three types of enterotoxaemia vaccines, namely toxoid (TV, alum precipitated (APV and alum precipitated oil adjuvant vaccine (AOV were prepared using a highly toxigenic strain of Clostridium perfringens type D procured from Division of Biological Standardization, IVRI, Izatnagar. Humoral immunity generated in rabbits with these vaccines was then quantified using indirect enzyme-linked immunosorbent assay (ELISA and mice neutralization test (MNT. Results: Out of three enterotoxaemia vaccines tested, alum precipitated oil adjuvant vaccine produced higher and persistent antibody titre for more than 45 days without any booster dose and did not produce any untoward reactions at the injection site. Alum precipitated vaccine elicited better and persistent immune response than toxoid vaccine though it was less than alum precipitated oil adjuvant vaccine. In MNT, alum precipitated and alum precipitated oil adjuvant vaccines showed protection at 45th day of post vaccination while toxoid vaccine showed only up to 28th day. Conclusion: Results of the study unfolded the synergistic role of adjuvants in the induction of better and persistent immune response and also indicated the superiority of alum precipitated oil adjuvant vaccine over the currently available toxoid and alum precipitated enterotoxaemia vaccines. [Vet World 2013; 6(4.000: 200-204
Østerhus, Sven Frederick
The Cochrane Library was systematically searched for meta-analyses regarding influenza vaccination of various populations, both healthy and sick. An effect in reducing the number of cases of influenza, influenza-like illness or complications to influenza was found in some studies, but, generally......, the quality of the studies was low, and several studies lacked hard clinical endpoints. Data on adverse effects were scarce. More randomised controlled trials investigating the effects of influenza vaccination are warranted....
... Types Seasonal Avian Swine/Variant Pandemic Other Flu Vaccine Safety Information Questions & Answers Language: English (US) Español ... of flu vaccines monitored? Egg Allergy Are flu vaccines safe? Flu vaccines have good safety record. Hundreds ...
... Avian Swine/Variant Pandemic Other Thimerosal in Flu Vaccine Questions & Answers Language: English (US) Español Recommend on ... or fungi from contaminating the vaccine. Do flu vaccines contain thimerosal? Flu vaccines in multi-dose vials ...
... Side Effects of Vaccination Who Should Get a Smallpox Vaccination? Bioterrorism The Threat Preparedness Detection and Response Bioterrorism ... Revaccinees Examples of Major or “Take” Reactions to Smallpox Vaccination Vaccine Adverse Reaction Images Laboratory Personnel Specimen Collection ...
... multi.html . CDC review information for Multi Pediatric Vaccines: Your Child's First Vaccines: What you need to know (VIS): ... of that vaccine. Tell the person giving the vaccines if your child has ever had a severe reaction after any ...
... 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 ...
Riedmann, Eva M.
Long-term effectiveness shown for Merck’s chickenpox vaccine Again—no link between vaccines and autism Experimental ovarian cancer vaccine successful in phase 1 Sinovac’s HFMD vaccine meets phase 3 study goal A vaccine for long-suffering cat allergy patients Vaccines are key to breaking infectious disease-malnutrition cycle Cancer vaccine failures due to the adjuvant IFA? Novartis’ typhoid vaccine make good progress
this profession for its role as vaccinator? Dentistry serves as an example of a branch of medicine whose practice is limited to the oral cavity... Medicine NCIRD National Center for Immunization and Respiratory Diseases NIMS National Incident Management System NSPD National Security Presidential...Cosmetic Act. Four of five pharmaceutical manufacturers are licensed to distribute vaccine for the U.S. market but produce vaccine in plants
Kunda, Nitesh K; Wafula, Denis; Tram, Meilinn; Wu, Terry H; Muttil, Pavan
Formulating vaccines into a dry form enhances its thermal stability. This is critical to prevent administering damaged and ineffective vaccines, and to reduce its final cost. A number of vaccines in the market as well as those being evaluated in the clinical setting are in a dry solid state; yet none of these vaccines have achieved long-term stability at high temperatures. We used spray-drying to formulate a recombinant live attenuated Listeria monocytogenes (Lm; expressing Francisella tularensis immune protective antigen pathogenicity island protein IglC) bacterial vaccine into a thermostable dry powder using various sugars and an amino acid. Lm powder vaccine showed minimal loss in viability when stored for more than a year at ambient room temperature (∼23°C) or for 180days at 40°C. High temperature viability was achieved by maintaining an inert atmosphere in the storage container and removing oxygen free radicals that damage bacterial membranes. Further, in vitro antigenicity was confirmed by infecting a dendritic cell line with cultures derived from spray dried Lm and detection of an intracellularly expressed protective antigen. A combination of stabilizing excipients, a cost effective one-step drying process, and appropriate storage conditions could provide a viable option for producing, storing and transporting heat-sensitive vaccines, especially in regions of the world that require them the most. Copyright © 2016 Elsevier B.V. All rights reserved.
Shibasaki, Seiji; Ueda, Mitsuyoshi
Oral vaccines are easier to administer than injectable vaccines. To induce an adequate immune response using vaccines, antigenic proteins are usually combined with adjuvant materials. This chapter presents methodologies for the design of oral vaccines using molecular display technology. In molecular display technology, antigenic proteins are displayed on a microbial cell surface with adjuvant ability. This technology would provide a quite convenient process to produce oral vaccines when the DNA sequence of an efficient antigenic protein is available. As an example, oral vaccines against candidiasis were introduced using two different molecular display systems with Saccharomyces cerevisiae and Lactobacillus casei.
Hepatitis-B vaccine, developed for the prevention of hepatitis-B virus infection, is a noninfectious recombinant. DNA vaccine produced from genetically engineered yeast named Saccharomyces cerevisiae. Although there has been modification in the production of the vaccine after its initial development in 1981, the ...
Jan 12, 2018 ... Expected results. By adopting this cutting-edge approach to the development of African swine fever vaccines, the overall expected result is the generation of a vaccine candidate that will undergo further testing and if successful, be produced as a new vaccine for ASF.
Innes, Elisabeth A; Bartley, Paul M; Maley, Stephen; Katzer, Frank; Buxton, David
Toxoplasma gondii has a very wide intermediate host range and is thought to be able to infect all warm blooded animals. The parasite causes a spectrum of different diseases and clinical symptoms within the intermediate hosts and following infection most animals develop adaptive humoral and cell-mediated immune responses. The development of protective immunity to T. gondii following natural infection in many host species has led researchers to look at vaccination as a strategy to control disease, parasite multiplication and establishment in animal hosts. A range of different veterinary vaccines are required to help control T. gondii infection which include vaccines to prevent congenital toxoplasmosis, reduce or eliminate tissue cysts in meat producing animals and to prevent oocyst shedding in cats. In this paper we will discuss some of the history, challenges and progress in the development of veterinary vaccines against T. gondii.
Elisabeth A Innes
Full Text Available Toxoplasma gondii has a very wide intermediate host range and is thought to be able to infect all warm blooded animals. The parasite causes a spectrum of different diseases and clinical symptoms within the intermediate hosts and following infection most animals develop adaptive humoral and cell-mediated immune responses. The development of protective immunity to T. gondii following natural infection in many host species has led researchers to look at vaccination as a strategy to control disease, parasite multiplication and establishment in animal hosts. A range of different veterinary vaccines are required to help control T. gondii infection which include vaccines to prevent congenital toxoplasmosis, reduce or eliminate tissue cysts in meat producing animals and to prevent oocyst shedding in cats. In this paper we will discuss some of the history, challenges and progress in the development of veterinary vaccines against T. gondii.
... Vaccines: The Basics Adult Vaccination Resources for Healthcare Professionals ... Influenza vaccine each year to protect against seasonal flu Tdap vaccine to protect against whooping cough and ...
... Vaccines: The Basics Adult Vaccination Resources for Healthcare Professionals ... Influenza vaccine each year to protect against seasonal flu Tdap vaccine to protect against whooping cough and ...
... Vaccines: The Basics Adult Vaccination Resources for Healthcare Professionals ... Influenza vaccine each year to protect against seasonal flu Tdap vaccine to protect against whooping cough and ...
Takeyama, Natsumi; Yuki, Yoshikazu; Kiyono, Hiroshi
Mucosal vaccination has several advantages compared with that of injection-type vaccination. Secretory IgA(SIgA) produced at mucosal surface plays a key role for inactivation of toxins and inhibition of pathogen invasion. Although oral or nasal vaccination with attenuated live microorganisms have been shown to be effective in the induction of protective immunity, these types of vaccine have the ability to infect transiently to the host. For the development of safe and effective mucosal vaccine, an obvious strategy is the preparation of inactivated subunit-type mucosal vaccine. Here we introduce our frontier technology for the development of rice-based oral vaccines, as a new generation of mucosal vaccine. Further, we also discuss recent progress in the development of other types of mucosal vaccine and adjuvant.
Diemert, David J; Bethony, Jeffrey M; Hotez, Peter J
Hookworm infection caused by the soil-transmitted nematodes Necator americanus and Ancylostoma duodenale is one of the most common parasitic infections worldwide. Although not directly responsible for substantial mortality, it causes significant morbidity in the form of chronic anemia and protein malnutrition. Current global control efforts based on periodic mass anthelmintic administration are unsustainable, and new control strategies must be developed. This review describes progress in the development of vaccines against hookworm infection, including the preclinical and initial clinical testing of the N. americanus Ancylostoma Secreted Protein-2 Hookworm Vaccine. Plans call for eventual development of a vaccine that will combine at least 2 hookworm antigens--one targeting the larval stage of the life cycle and another targeting the adult worm living in the gastrointestinal tract.
Nizard, Mevyn; Diniz, Mariana O; Roussel, Helene; Tran, Thi; Ferreira, Luis CS; Badoual, Cecile; Tartour, Eric
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
Barry, Eileen M.; Pasetti, Marcela F.; Sztein, Marcelo B.; Fasano, Alessio; Kotloff, Karen L.; Levine, Myron M.
Renewed awareness of the significant morbidity and mortality that Shigella causes among young children in developing countries combined with technological innovations in vaccinology has led to the development of novel vaccine strategies in the past five years. Along with advancement of classical vaccines in clinical trials and new sophisticated measurements of immunological responses, much new data has been produced lending promise to the potential for production of safe and effective Shigella vaccines. Herein we review the recent progress in Shigella vaccine development within the framework of persistent obstacles. PMID:23419287
Ma, J K
A vaccine against dental caries, for so long a subject of purely academic research, is currently undergoing phase II clinical trials and could be available commercially within 5 to 6 years. The approach, which is safe, effective, and provides long-term protection for up to a year, is based on a topical application and does not require any injections. The development of this vaccine has been made possible by recent advances in molecular biology and genetic engineering. Perhaps one of the most intriguing aspects has been the use of green plants to produce the vaccine. This article describes a topical vaccine against Streptococcus mutans, which is the main cause of dental caries.
Mones S. Abu-Asab
Full Text Available Posttrial assessment of a vaccine's selective pressure on infecting strains may be realized through a bioinformatic tool such as parsimony phylogenetic analysis. Following a failed gonococcal pilus vaccine trial of Neisseria gonorrhoeae, we conducted a phylogenetic analysis of pilin DNA and predicted peptide sequences from clinical isolates to assess the extent of the vaccine's effect on the type of field strains that the volunteers contracted. Amplified pilin DNA sequences from infected vaccinees, placebo recipients, and vaccine specimens were phylogenetically analyzed. Cladograms show that the vaccine peptides have diverged substantially from their paternal isolate by clustering distantly from each other. Pilin genes of the field clinical isolates were heterogeneous, and their peptides produced clades comprised of vaccinated and placebo recipients' strains indicating that the pilus vaccine did not exert any significant selective pressure on gonorrhea field strains. Furthermore, sequences of the semivariable and hypervariable regions pointed out heterotachous rates of mutation and substitution.
Dixon, Graham N
Health officials often face challenges in communicating the risks associated with not vaccinating, where persuasive messages can fail to elicit desired responses. However, the mechanisms behind these failures have not been fully ascertained. To address this gap, an experiment (N = 163) tested the differences between loss-framed messages-one emphasizing the consequence of not receiving a flu vaccine; the other emphasizing the consequence of receiving the flu vaccine. Despite an identical consequence (i.e., Guillain-Barre syndrome), the message highlighting the consequence of not receiving the flu vaccine produced lower negative affect scores as compared to the message highlighting the consequence of receiving the flu vaccine. Mediation analyses suggest that one reason for this difference is due to non-vaccination being perceived as temporary and reversible, whereas vaccination is perceived as being permanent. Implications on health communication and future research are discussed.
... cholera, hepatitis-B, and many more are in the process of development. Food vaccines may also help to suppress autoimmunity disorders such as Type-1 Diabetes. Key words: Edible vaccines, oral vaccines, antigen expression, food vaccines. African Journal of Biotechnology Vol. 2 (12), pp. 679-683, December 2003 ...
Edible vaccines are sub-unit vaccines where the selected genes are introduced into the plants and the transgenic plant is then induced to manufacture the encoded protein. Edible vaccines are mucosal-targeted vaccines where stimulation of both systematic and mucosal immune network takes place. Foods under study ...
Full Text Available Hyperuricemia (HUA is related to diabetes. Uric acid-induced inflammation and oxidative stress are risk factors for diabetes and its complications. Human urate transporter 1 (URAT1 regulates the renal tubular reabsorption of uric acid. IA-2(5-P2-1, a potent immunogenic carrier designed by our laboratory, can induce high-titer specific antibodies when it carries a B cell epitope, such as B cell epitopes of DPP4 (Dipeptidyl peptidase-4, xanthine oxidase. In this report, we describe a novel multi-epitope vaccine composing a peptide of URAT1, an anti-diabetic B epitope of insulinoma antigen-2(IA-2 and a Th2 epitope (P2:IPALDSLTPANED of P277 peptide in human heat shock protein 60 (HSP60. Immunization with the multi-epitope vaccine in streptozotocin-induced diabetes C57BL/6J mice successfully induced specific anti-URAT1 antibody, which inhibited URAT1 action and uric acid reabsorption, and increased pancreatic insulin level with a lower insulitis incidence. Vaccination with U-IA-2(5-P2-1 (UIP-1 significantly reduced blood glucose and uric acid level, increased Th2 cytokines interleukin (IL-10 and IL-4, and regulated immune reactions through a balanced Th1/Th2 ratio. These results demonstrate that the URAT1-based multi-epitope peptide vaccine may be a suitable therapeutic approach for diabetes and its complications.
Bowman, Darcia Harris
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…
Bärnighausen, Till; Bloom, David E.; Cafiero-Fonseca, Elizabeth T.; O’Brien, Jennifer Carroll
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
research interests include: eukaryotic gene expres- sion and infectious diseases. Keywords. DNA vaccine, immune response, antibodies, infectious diseases. GENERAL I ... T -cells: Lymphocytes that differentiate primarily in the thymus and are central to the control and ... enhance DNA delivery into skeletal muscle.
Full Text Available Vaccination remains the principal way to control seasonal infections and is the most effective method of reducing influenza-associated morbidity and mortality. Since the 1940s, the main method of producing influenza vaccines has been an egg-based production process. However, in the event of a pandemic, this method has a significant limitation, as the time lag from strain isolation to final dose formulation and validation is six months. Indeed, production in eggs is a relatively slow process and production yields are both unpredictable and highly variable from strain to strain. In particular, if the next influenza pandemic were to arise from an avian influenza virus, and thus reduce the egg-laying hen population, there would be a shortage of embryonated eggs available for vaccine manufacturing. Although the production of egg-derived vaccines will continue, new technological developments have generated a cell-culture-based influenza vaccine and other more recent platforms, such as synthetic influenza vaccines.
Borhani, Kiandokht; Ajorloo, Mehdi; Bamdad, Taravat; Mozhgani, Sayed Hamid Reza; Ghaderi, Mostafa; Gholami, Ali Reza
Rabies is a widespread neurological zoonotic disease causing significant mortality rates, especially in developing countries. Although a vaccine for rabies is available, its production and scheduling are costly in such countries. Advances in recombinant DNA technology have made it a good candidate for an affordable vaccine. Among the proteins of rabies virus, the Glycoprotein (RVG) has been the major target for new vaccine development which plays the principal role in providing complete protection against RV challenge. The aim of this study is to produce recombinant RVG which could be a DNA vaccine candidate and to evaluate the efficiency of this construct in a prime-boost vaccination regimen, compared to commercial vaccine. Cloning to pcDNA3.1(+) and expression of rabies virus glycoprotein gene in BSR cell line were performed followed by SDS-PAGE and Western blot analysis of the expressed glycoprotein. The resulting genetic construct was used as a DNA vaccine by injecting 80 µg of the plasmid to MNRI mice twice. Prime-Boost vaccination strategy was performed using 80 µg plasmid construct as prime dose and the second dose of an inactivated rabies virus vaccine. Production of rabies virus neutralizing antibody (RVNA) titers of the serum samples were determined by RFFIT. In comparisons between heterologous prime-boost vaccination strategy and DNA vaccinations, the potency of group D that received Prime-Boost vaccine with the second dose of pcDNA3.1(+)-Gp was enhanced significantly compared to the group C which had received pcDNA3.1(+)-Gp as first injection. In this study, RVGP expressing construct was used in a comparative approach between Prime-Boost vaccination strategy and DNA vaccination and compared with the standard method of rabies vaccination. It was concluded that this strategy could lead to induction of acceptable humoral immunity.
The situation of viral vaccines used in Asian countries is reviewed, focusing on the following vaccines: smallpox, rabies, polio, measles, rubella, mumps, influenza, Japanese encephalitis, hepatitis B, varicella, dengue, and rotavirus. Vaccinations are among the most important strategies to combat communicable diseases caused by bacteria, fungi, parasites, and viruses. Active immunizations are more preferable in most instances than passive ones. It has taken almost 2 centuries to eradicate the highly contagious infection of smallpox from the world. In 1979 the World Health Organization (WHO) announced the global eradication of smallpox. Smallpox vaccination was 1st practiced in 1840 by Dr. Dan Beach Bradley, with the last 2 cases of smallpox reported in Thailand in 1962. Despite the achievement for many years of more ideal rabies vaccine, Semple vaccine continues to be used in developing countries. Attempts should be intensified to produce newer tissue culture vaccines in developing countries themselves and to eradicate vectors. Instances of poliomyelitis were reported in Indonesia, the Philippines, Sri Lanka, India, and Thailand as late as 1983-84, but only a few sporadic cases have occurred in Malaysia since 1980. This mixed record results from polio vaccine having been incorporated into national Expanded Program on Immunization (EPI) programs in many countries. Measles remains 1 of the most common viral infections in children in most developing nations, but morbidity and mortality rates are not accurately obtainable in these countries. Rubella outbreaks have been reported from many countries in Southeast Asia with congenital rubella syndromes due to maternal rubella on the increase in many countries, including Thailand. Children who receive the mumps vaccination are those receiving the combined MMR vaccines. Monovalent mumps vaccine is not obtainable in developing countries. Influenza vaccine is impracticable in most developing countries. Japanese encephalitis
Estimation of reactogenicity of preparations produced on the basis of photoinactivated live vaccines against brucellosis and tularaemia on the organismic level.2. Using the method of speckle-microscopy with high spatial resolution
Ulianova, O. V.; Uianov, S. S.; Li, Pengcheng; Luo, Qingming
The method of speckle microscopy was adapted to estimate the reactogenicity of the prototypes of vaccine preparations against extremely dangerous infections. The theory is proposed to describe the mechanism of formation of the output signal from the super-high spatial resolution speckle microscope. The experimental studies show that bacterial suspensions, irradiated in different regimes of inactivation, do not exert negative influence on the blood microcirculations in laboratory animals.
S.A. Khan, S.M. Subtain, A. Aslam, K. Muhammad1 and K.A. Khan
Full Text Available One hundred and sixty one-day-old layer chicks were divided into four experimental groups A, B, C and D, with 40 birds in each group. Group A was kept as control (non-vaccinated, group B was given vaccine but not medicated, group C was administered vaccine as well as multivitamins for 3 days post-vaccination, while group D was also medicated with aspirin for 3 days post-vaccination. The parameters studied were: heterophil/lymphocyte ratio, serum biochemical analysis (serum protein, glucose and cholesterol, antibody response against infectious bursal disease virus (IBDV. At the end of experiment (42nd day adrenal glands from 10 randomly selected birds from each group were subjected to gross and histopathological examination and adrenal/body weight ratio was also determined. The results showed non significant difference among different groups. However, the group that was given multivitamins showed maximum immune response against IBDV, while the aspirin therapy did not show any significant difference. It can be concluded that vaccine produced undetectable stress in layer chicks and the vitamin supplementation evidently showed as an immuno-potentiating effect
Milstien, Julie; Schmitt, Sarah
Abstract Brazil, the Russian Federation, India, China and South Africa – the countries known as BRICS – have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector’s price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS’ accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes. PMID:24940018
... Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More sharing options ... the primary immunization series in infants Report Adverse Event Report a Vaccine Adverse Event Contact FDA (800) ...
Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at http://www.cdc.gov/hpv. HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...
Home | 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 ...
... value="Submit" /> Related Links Vaccines & Immunizations Current Vaccine Shortages & Delays Recommend on Facebook Tweet Share Compartir ... vaccination are included in this update. Chart of Vaccines* in Delay or Shortage National Vaccine Supply Shortages ...
The isolation of influenza virus 80 years ago in 1933 very quickly led to the development of the first generation of live-attenuated vaccines. The first inactivated influenza vaccine was monovalent (influenza A). In 1942, a bivalent vaccine was produced after the discovery of influenza B. It was later discovered that influenza viruses mutated leading to antigenic changes. Since 1973, the WHO has issued annual recommendations for the composition of the influenza vaccine based on results from surveillance systems that identify currently circulating strains. In 1978, the first trivalent vaccine included two influenza A strains and one influenza B strain. Currently, there are two influenza B lineages circulating; in the latest WHO recommendations, it is suggested that a second B strain could be added to give a quadrivalent vaccine. The history of influenza vaccine and the associated technology shows how the vaccine has evolved to match the evolution of influenza viruses.
Lyke, Kirsten E
Great progress has been made in reducing malaria morbidity and mortality, yet the parasite continues to cause a startling 200 million infections and 500 000 deaths annually. Malaria vaccine development is pushing new boundaries by steady advancement toward a licensed product. Despite 50 years of research, the complexity of Plasmoidum falciparum confounds all attempts to eradicate the organism. This very complexity has pushed the boundaries of vaccine development to new heights, yet it remains to be seen if an affordable vaccine can provide durable and high-level protection. Novel vaccines such as RTS,S/AS01E are on the edge of licensure, but old techniques have resurged with the ability to deliver vialed, whole organism vaccines. Novel adjuvants, multistage/multiantigen approaches and transmission blocking vaccines all contribute to a multipronged battle plan to conquer malaria. Vaccines are the most cost-effective tools to control infectious diseases, yet the complexity of malaria has frustrated all attempts to develop an effective product. This review concentrates on recent advances in malaria vaccine development that lend hope that a vaccine can be produced and malaria eradicated.
Pinn Tsin Isabel Yee
Full Text Available The hand, foot and mouth disease is caused by a group of Enteroviruses such as Enterovirus 71 (EV-A71 and Coxsackievirus CV-A5, CV-A8, and CV-A16. Mild symptoms of EV-A71 infection in children range from high fever, vomiting, rashes and ulcers in mouth but can produce more severe symptoms such as brainstem and cerebellar encephalitis, leading up to cardiopulmonary failure and death. The lack of vaccines and antiviral drugs against EV-A71 highlights the urgency of developing preventive and treatment agents against EV-A71 to prevent further fatalities. Research groups have developed experimental inactivated vaccines, recombinant Viral Protein 1 (VP1 vaccine and virus-like particles (VLPs. The inactivated EV-A71 vaccine is considered the safest viral vaccine, as there will be no reversion to the infectious wild type strain. The recombinant VP1 vaccine is a cost-effective immunogen, while VLPs contain an arrangement of epitopes that can elicit neutralizing antibodies against the virus. As each type of vaccine has its advantages and disadvantages, increased studies are required in the development of such vaccines, whereby high efficacy, long-lasting immunity, minimal risk to those vaccinated, safe and easy production, low cost, dispensing the need for refrigeration and convenient delivery are the major goals in their design.
Brito, Luis A; Kommareddy, Sushma; Maione, Domenico; Uematsu, Yasushi; Giovani, Cinzia; Berlanda Scorza, Francesco; Otten, Gillis R; Yu, Dong; Mandl, Christian W; Mason, Peter W; Dormitzer, Philip R; Ulmer, Jeffrey B; Geall, Andrew J
This chapter provides a brief introduction to nucleic acid-based vaccines and recent research in developing self-amplifying mRNA vaccines. These vaccines promise the flexibility of plasmid DNA vaccines with enhanced immunogenicity and safety. The key to realizing the full potential of these vaccines is efficient delivery of nucleic acid to the cytoplasm of a cell, where it can amplify and express the encoded antigenic protein. The hydrophilicity and strong net negative charge of RNA impedes cellular uptake. To overcome this limitation, electrostatic complexation with cationic lipids or polymers and physical delivery using electroporation or ballistic particles to improve cellular uptake has been evaluated. This chapter highlights the rapid progress made in using nonviral delivery systems for RNA-based vaccines. Initial preclinical testing of self-amplifying mRNA vaccines has shown nonviral delivery to be capable of producing potent and robust innate and adaptive immune responses in small animals and nonhuman primates. Historically, the prospect of developing mRNA vaccines was uncertain due to concerns of mRNA instability and the feasibility of large-scale manufacturing. Today, these issues are no longer perceived as barriers in the widespread implementation of the technology. Currently, nonamplifying mRNA vaccines are under investigation in human clinical trials and can be produced at a sufficient quantity and quality to meet regulatory requirements. If the encouraging preclinical data with self-amplifying mRNA vaccines are matched by equivalently positive immunogenicity, potency, and tolerability in human trials, this platform could establish nucleic acid vaccines as a versatile new tool for human immunization. Copyright © 2015 Elsevier Inc. All rights reserved.
... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)
Starr, S Paul
A new 9-valent human papillomavirus (HPV) vaccine is effective against more cancer-causing HPV types than previous vaccines. HPV vaccine series started with previous vaccines can be completed with the 9-valent vaccine. Two new influenza vaccines are available for adults 65 years and older: a high-dose vaccine and an enhanced adjuvant vaccine. These elicit stronger antibody responses than standard-dose vaccines. Current guidelines specify no preference for the new versus standard-dose vaccines. Two new group B meningococcal vaccines are intended for use during outbreaks and for patients with asplenia, complement deficiencies, frequent occupational meningococcus exposure, or for patients who desire protection from type B meningococcus. These are not substitutes for the quadrivalent vaccine already in use. For pneumococcus, new recommendations state that 13-valent pneumococcal conjugate vaccine (PCV13) should be administered to patients 65 years and older, followed at least 1 year later by the polyvalent pneumococcal polysaccharide vaccine (PPSV23). For patients ages 19 to 64 years with immunocompromise and not previously vaccinated against pneumococcus, administration of these two vaccines should be separated by at least 8 weeks. Rotavirus vaccine is standard for infants at age 2 months. Also, there is a new cholera vaccine approved for use in the United States. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.
Wielink, van R.
Vaccination of poultry can be used as a tool to control outbreaks of avian influenza, including that of highly pathogenic H5 and H7 strains. Influenza vaccines are traditionally produced in embryonated chicken eggs. Continuous cell lines have been suggested as an alternative substrate to produce
Saluja, Vinay; Hinrichs, Wouter L. J.; Frijlink, Henderik W.
Since last year influenza pandemic has struck again after 40 years, this is the right moment to discuss the different available formulation options for influenza vaccine. Looking back to the last 4 decades, most vaccines are still formulated as liquid solution. These vaccines have shown a poor
Jahanbakhsh Sefidi, Fatemeh; Kaghazian, Homan; Moradli, Gholam Ali; Hassanzadeh, Seyed Mehdi
Thermal stability (TS) is a part of the BCG vaccine characterization by which the consistency of process in BCG vaccine production could be confirmed. To enhance the TS of the vaccine, some prevalent stabilizers in different concentrations were added to the final formulation of BCG bulk prior to Freeze-drying process. We found a formulation more effective than the current stabilizer for retaining the higher viability of lyophilized BCG vaccine produced by Pasteur Institute of Iran. In the design of experiments using Taguchi method, lactose, trehalose, glucose, dextran, and monosodium glutamate were added to the final formulation of BCG bulk prior to freeze-drying process. Viability of the samples was determined by counting the colony forming unit. Maximum signal-to-noise ratio equal to maximum TS and viability was obtained by adding lactose, dextran, and glutamate in defined concentrations. Adding the stabilizers had a significant impact on TS of BCG vaccine to meet the quality requirements.
Ompad, Danielle C; Galea, Sandro; Blaney, Shannon; Coady, Micaela H; Sisco, Sarah; Glidden, Kathryn; Vlahov, David
In October 2004, one of the major producers of the U.S. influenza vaccine supply announced that their vaccine would not be available because of production problems, resulting in approximately half of the anticipated supply suddenly becoming unavailable. This study was part of a larger effort using community-based participatory research (CBPR) principles to distribute influenza vaccine to hard-to-reach populations. Given the extant literature suggesting economic and racial disparities in influenza vaccine access in times of adequate supply and our inability to distribute vaccine due to the shortage, we sought to examine vaccine access as well as awareness of the vaccine shortage and its impact on health-seeking behaviors in eight racially-diverse and economically-disadvantaged neighborhoods in New York City (NYC) during the shortage. In our study few people had been vaccinated, both among the general community and among high risk groups; vaccination rates for adults in priority groups and non-priority groups were 21.0% and 3.5%. Awareness of the 2004 vaccine shortage was widespread with over 90% being aware of the shortage. While most attributed the shortage to production problems, almost 20% said that it was due to the government not wanting to make the vaccine available. Many respondents said they would be more likely to seek vaccination during the current and subsequent influenza seasons because of the shortage. The target neighborhoods were significantly affected by the national influenza vaccine shortage. This study highlights the challenges of meeting the preventive health care needs of hard-to-reach populations in times of public health crisis.
The Nigerian government is butting heads with Dr. Jeremiah Abalaka over Abalaka's AIDS vaccine, with the government taking the latest hit. Abalaka claims to have successfully produced a vaccine that can reduce or cure HIV. The vaccine has been administered to infected people, with adverse results, the government claims. According to a report in Nigeria's Post Express newspaper ("Nigeria: Why We Stopped Use of the Vaccines-Atiku", Post Express (Lagos) July 25, 2000, by Obiorah Ifo), the country's vice president, Alhaji Atiku Abubakar, said the government has stepped in to stop Abalaka from administering the vaccine "because it has killed more people than it has cured". The newspaper quoted him saying that it was only in Nigeria that "somebody can go and manufacture vaccine without permission and authorization of the drug administration of the country before he can begin to administer it on Nigerians". Then on July 31, 2000, the Federal Court of Appeal backed Abalaka and ordered that the government stop investigating the vaccine. "The court, presided over by Justice Muntaka Coomassie, also granted an interim order restraining the defendant from taking any action on Dr. Abalaka pending the hearing of the motion on notice", said an article in the Vanguard Daily newspaper ("Court halts federal government over Abalaka's HIV vaccine", Vanguard Daily (Lagos) July 31, 2000, by Bukola Ojeme). The government's primary complaint is that Abalaka reportedly would not back his claims for the vaccine with proper scientific data. A team of medical experts found "the vaccine could not pass through any acceptable criteria", the Post Express report said, and so the government had ordered that use of the vaccine cease. According to Abubakar, the vaccine "has caused more havoc, it has killed people, and it will kill more. That is when the government decided to intervene. Meanwhile, the man is busy administering the vaccine and people are dying", the Post Express quoted him as saying
Waterbeemd, van de B.
Only vaccines containing outer membrane vesicles (OMV) have successfully stopped Neisseria meningitidis serogroup B epidemics. The OMV vaccines, however, provide limited coverage and are difficult to produce. This is caused by an obligatory detergent treatment, which removes lipopolysaccharide
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.
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.
... Barcodes Related Link Vaccines & Immunizations Immunization Schedules Your Child's First Vaccines Format: Select One PDF [336K] RTF [260K] Recommend ... of that vaccine. Tell the person giving the vaccines if your child has ever had a severe reaction after any ...
Bioterrorist attacks occupy a special place amongst the innumerable potential types of terrorist attack, with the intentional release of pox viruses being especially feared in this connection. Apart from the variola virus, the agent responsible for smallpox in humans, the monkeypox virus and numerous other animal pox viruses pose potential risks for humans and animals. This risk scenario also includes recombinations between the various pox viruses, changes in hosts and genetically engineered manipulations of pox viruses. For over 200 years, the method of choice for combatting smallpox was via vaccination with a reproductive, original vaccinia virus. Worldwide eradication of smallpox at the end of the 1970s and the discontinuation of routine smallpox vaccination in 1980 can be credited to such vaccination. Unfortunately, these vaccinations were associated with a large number of postvaccinal impairments, sometimes resulting in death (e.g. postvaccinal encephalitis). The only way to restrict such postvaccinal complications was to carry out initial vaccination within the first 2 postnatal years. Initial vaccination at a later age led to such a sharp increase in the number of vaccines with complications that vaccination had to be discouraged. The dilemma of the smallpox vaccine stocks stems from the fact that a large portion of these stocks are produced with the same vaccinia strains as before. This is irresponsible, especially as the percentage of immune-suppressed persons in the population, for whom vaccination-related complications pose an especial threat, is increasing. One solution to the dilemma of the smallpox vaccine stocks is the MVA strain. It is harmless, protects humans and animals equally well against smallpox and can be applied parenterally.
Preiss, Scott; Garçon, Nathalie; Cunningham, Anthony L; Strugnell, Richard; Friedland, Leonard R
The administration of a vaccine to a recipient is the final step in a development and production process that may have begun several decades earlier. Here we describe the scale and complexity of the processes that brings a candidate vaccine through clinical development to the recipient. These challenges include ensuring vaccine quality (between 100 and 500 different Quality Control tests are performed during production to continually assess safety, potency and purity); making decisions about optimal vaccine presentation (pre-filled syringes versus multi-dose vials) that affect capacity and supply; and the importance of maintaining the vaccine cold chain (most vaccines have stringent storage temperature requirements necessary to maintain activity and potency). The ultimate aim is to make sure that an immunogenic product matching the required specifications reaches the recipient. The process from concept to licensure takes 10-30years. Vaccine licensure is based on a file submitted to regulatory agencies which contains the comprehensive compilation of chemistry, manufacturing information, assay procedures, preclinical and clinical trial results, and proposals for post-licensure effectiveness and safety data collection. Expedited development and licensure pathways may be sought in emergency settings: e.g., the 2009 H1N1 influenza pandemic, the 2014 West African Ebola outbreak and meningococcal serogroup B meningitis outbreaks in the United States and New Zealand. Vaccines vary in the complexity of their manufacturing process. Influenza vaccines are particularly challenging to produce and delays in manufacturing may occur, leading to vaccine shortages during the influenza season. Shortages can be difficult to resolve due to long manufacturing lead times and stringent, but variable, local regulations. New technologies are driving the development of new vaccines with simplified manufacturing requirements and with quality specifications that can be confirmed with fewer
Full Text Available Vaccination aided disease control over infection pathology among the children led to elimination of smallpox and poliomyelitis, drastic decrease of the tuberculous meningitis recurrences, tetanus, measles and other infection diseases and their complications. At the same time, Russia is still afraid to apply certain vaccines. The reasons for that are mainly subjective. This is the unjustified caution related to the fear that it may cause severe vaccine associated complications. The data in view of the lecture indicates the safety of the vaccinal prevention procedures and measures for the prevention of their complications.Key words: vaccinal prevention, vaccination complications, vaccination safety, children.
Chettri, Jiwan Kumar
significant losses in aquacultural enterprises but vaccination methods implemented since the 1990s have demonstrated their role as one of the most efficient disease control strategies. These have been particularly successful with regard to bacterial diseases in Norwegian salmon farming where multivalent...... vaccines have reduced the need for usage of antibiotics with more than 99 % since the 1980s. Fish can be vaccinated by three different administration routes: injection, immersion and oral vaccination. Injection vaccination (intraperitoneal injection of vaccine) is the most time consuming and labor...... intensive method, which however, provides the best protection of the fish. Immersion vaccination is used for immunization of a high number of small fish is cost-efficient and fast (30 sec immersion into vaccine). Oral vaccination (vaccine in feed) is the least efficient. As in higher vertebrates fish...
Elsedawy, Noura B; Russell, Stephen J
Oncolytic viruses are ideal platforms for tumor vaccination because they can mediate the direct in situ killing of tumor cells that release a broad array of tumor antigens and alarmins or danger signals thereby cross-priming antitumor cytotoxic T lymphocytes (CTLs), which mediate the indirect killing of uninfected cells. The balance between the direct and indirect killing phases of oncolytic virotherapy is the key to its success and can be manipulated by incorporating various immunomodulatory genes into the oncolytic virus genome. Recently, the interim analysis of a large multicenter Phase III clinical trial for Talimogene laherparepvec, a granulocyte-macrophage colony stimulating factor-armed oncolytic herpes simplex virus, revealed significant improvement in objective response and durable response rates over control arm and a trend toward improved overall survival. Meanwhile, newer oncolytics are being developed expressing additional immunomodulatory transgenes to further enhance cross-priming and the generation of antitumor CTLs and to block the immunosuppressive actions of the tumor microenvironment. Since oncolytic vaccines can be engineered to kill tumor cells directly, modulate the kinetics of the antitumor immune response and reverse the immunosuppressive actions of the tumor, they are predicted to emerge as the preferred immunotherapeutic anticancer weapons of the future.
Full Text Available The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines.
Velmurugan, Kamalakannan; Grode, Leander; Chang, Rosemary; Fitzpatrick, Megan; Laddy, Dominick; Hokey, David; Derrick, Steven; Morris, Sheldon; McCown, David; Kidd, Reginald; Gengenbacher, Martin; Eisele, Bernd; Kaufmann, Stefan H E; Fulkerson, John; Brennan, Michael J
The failure of current Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG) strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO) from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO) from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines.
Philip D. Minor
Full Text Available The potency of vaccines must be determined to ensure that the appropriate dose is given. The manufacture and assessment of influenza vaccines are complicated by the continuously changing nature of the pathogen, which makes efficacy estimates difficult but also confounds attempts to produce a well-validated, consistent potency assay. Single radial diffusion has been used for decades and provides a relatively simple way to measure the amount of biologically active materials present in the vaccine. It requires reagents, which are updated on a regular, frequently yearly, basis and alternative methods continue to be sought.
Munang’andu, Hetron Mweemba; Paul, Joydeb; Evensen, Øystein
Streptococcus agalactiae is an emerging infectious disease adversely affecting Nile tilapia (Niloticus oreochromis) production in aquaculture. Research carried out in the last decade has focused on developing protective vaccines using different strategies, although no review has been carried out to evaluate the efficacy of these strategies. The purpose of this review is to provide a synopsis of vaccination strategies and antigen delivery systems currently used for S. agalactiae vaccines in tilapia. Furthermore, as shown herein, current vaccine designs include the use of replicative antigen delivery systems, such as attenuated virulent strains, heterologous vectors and DNA vaccines, while non-replicative vaccines include the inactivated whole cell (IWC) and subunit vaccines encoding different S. agalactiae immunogenic proteins. Intraperitoneal vaccination is the most widely used immunization strategy, although immersion, spray and oral vaccines have also been tried with variable success. Vaccine efficacy is mostly evaluated by use of the intraperitoneal challenge model aimed at evaluating the relative percent survival (RPS) of vaccinated fish. The major limitation with this approach is that it lacks the ability to elucidate the mechanism of vaccine protection at portals of bacterial entry in mucosal organs and prevention of pathology in target organs. Despite this, indications are that the correlates of vaccine protection can be established based on antibody responses and antigen dose, although these parameters require optimization before they can become an integral part of routine vaccine production. Nevertheless, this review shows that different approaches can be used to produce protective vaccines against S. agalactiae in tilapia although there is a need to optimize the measures of vaccine efficacy. PMID:27983591
Munang'andu, Hetron Mweemba; Paul, Joydeb; Evensen, Øystein
Streptococcus agalactiae is an emerging infectious disease adversely affecting Nile tilapia (Niloticus oreochromis) production in aquaculture. Research carried out in the last decade has focused on developing protective vaccines using different strategies, although no review has been carried out to evaluate the efficacy of these strategies. The purpose of this review is to provide a synopsis of vaccination strategies and antigen delivery systems currently used for S. agalactiae vaccines in tilapia. Furthermore, as shown herein, current vaccine designs include the use of replicative antigen delivery systems, such as attenuated virulent strains, heterologous vectors and DNA vaccines, while non-replicative vaccines include the inactivated whole cell (IWC) and subunit vaccines encoding different S. agalactiae immunogenic proteins. Intraperitoneal vaccination is the most widely used immunization strategy, although immersion, spray and oral vaccines have also been tried with variable success. Vaccine efficacy is mostly evaluated by use of the intraperitoneal challenge model aimed at evaluating the relative percent survival (RPS) of vaccinated fish. The major limitation with this approach is that it lacks the ability to elucidate the mechanism of vaccine protection at portals of bacterial entry in mucosal organs and prevention of pathology in target organs. Despite this, indications are that the correlates of vaccine protection can be established based on antibody responses and antigen dose, although these parameters require optimization before they can become an integral part of routine vaccine production. Nevertheless, this review shows that different approaches can be used to produce protective vaccines against S. agalactiae in tilapia although there is a need to optimize the measures of vaccine efficacy.
Feng, Luzhao; Mounts, Anthony Wayne; Feng, Yunxia; Luo, Yuan; Yang, Peng; Feng, Zijian; Yang, Weizhong; Yu, Hongjie
To better understand the gap between limited influenza vaccine supply and the target population for vaccination in China, we conducted a retrospective survey to quantify the production capacity, supply and sale of seasonal trivalent inactive vaccine (TIV) from the 2004-2005 through the 2008-2009 season, and estimated the target population who should receive annual influenza vaccine. The maximum domestic capacity to produce TIV was 126 million doses in 2009. A total of 32.5 million doses of TIV were supplied in 2008-2009, with an average annual increase rate of 18% from 16.9 million in 2004-2005. This represents an amount sufficient to vaccinate 1.9% of Chinese population. The average number of doses of TIV for sale by province ranged from policies in some provinces. Based on national recommendations, we estimated a target population of 570.6 million or 43% of the total population. Supply and domestic production capacity for influenza vaccine is currently insufficient to vaccinate the estimated target population in China. The Government of China should consider measures to improve domestic production capacity of influenza vaccine, expand successful promotional campaigns, and add cost subsidies in high risk groups to further encourage influenza vaccine usage. Copyright © 2010 Elsevier Ltd. All rights reserved.
During the past thirty years, vaccines have experienced a renaissance. Advances in science, business, and distribution have transformed the field to the point where vaccines are recognized as a "best buy" in global health, a driver of pharmaceutical industry growth, and a key instrument of international development. With many new vaccines available and others on the horizon, the global community will need to explore new ways of ensuring access to vaccines in developing nations. So-called tiered pricing, which makes vaccines available at different prices for countries at different levels of economic development; innovative financing mechanisms such as advance market commitments or offers of long-term and high-volume contracts to vaccine producers; and technology transfers such as sharing intellectual property and production techniques among companies and countries can all play a part in bringing new life-saving vaccines for pneumonia, rotavirus, malaria, and other diseases to developing countries.
Monteiro, Mariana P
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.
de Melker, Hester; Kenter, Gemma; van Rossum, Tekla; Conyn-van Spaendonck, Marina
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.
MedImmune Vaccines (formerly Aviron) has developed a cold-adapted live influenza virus vaccine [FluMist] that can be administered by nasal spray. FluMist is the first live virus influenza vaccine and also the first nasally administered vaccine to be marketed in the US. The vaccine will be formulated to contain live attenuated (att) influenza virus reassortants of the strains recommended by the US Public Health Service for each 'flu season. The vaccine is termed cold-adapted (ca) because the virus has been adapted to replicate efficiently at 25 degrees C in the nasal passages, which are below normal body temperature. The strains used in the seasonal vaccine will also be made temperature sensitive (ts) so that their replication is restricted at 37 degrees C (Type B strains) and 39 degrees C (Type A strains). The combined effect of the antigenic properties and the att, ca and ts phenotypes of the influenza strains contained in the vaccine enables the viruses to replicate in the nasopharynx to produce protective immunity. The original formulation of FluMist requires freezer storage throughout distribution. Because many international markets do not have distribution channels well suited to the sale of frozen vaccines, Wyeth and MedImmune are collaborating to develop a second generation, refrigerator-stable, liquid trivalent cold-adapted influenza vaccine (CAIV-T), which is in phase III trials. Initially, the frozen formulation will only be available in the US. For the 2003-2004 season, FluMist will contain A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2) (A/Moscow/10/99-like) and B/Hong Kong/330/2001. Aviron was acquired by MedImmune on 15 January 2002. Aviron is now a wholly-owned subsidiary of MedImmune and is called MedImmune Vaccines. Aviron acquired FluMist in March 1995 through a Co-operative Research and Development Agreement (CRADA) with the US NIAID, and a licensing agreement with the University of Michigan, Ann Arbor, USA. In June 2000, the CRADA was
Miravalle, Augusto A; Schreiner, Teri
This chapter reviews the most common neurologic disorders associated with common vaccines, evaluates the data linking the disorder with the vaccine, and discusses the potential mechanism of disease. A literature search was conducted in PubMed using a combination of the following terms: vaccines, vaccination, immunization, and neurologic complications. Data were also gathered from publications of the American Academy of Pediatrics Committee on Infectious Diseases, the World Health Organization, the US Centers for Disease Control and Prevention, and the Vaccine Adverse Event Reporting System. Neurologic complications of vaccination are rare. Many associations have been asserted without objective data to support a causal relationship. Rarely, patients with a neurologic complication will have a poor outcome. However, most patients recover fully from the neurologic complication. Vaccinations have altered the landscape of infectious disease. However, perception of risk associated with vaccinations has limited the success of disease eradication measures. Neurologic complications can be severe, and can provoke fear in potential vaccines. Evaluating whether there is causal link between neurologic disorders and vaccinations, not just temporal association, is critical to addressing public misperception of risk of vaccination. Among the vaccines available today, the cost-benefit analysis of vaccinations and complications strongly argues in favor of vaccination. © 2014 Elsevier B.V. All rights reserved.
Full Text Available Simple and effective vaccine administration is particularly important for annually recommended influenza vaccination. We hypothesized that vaccine delivery to the skin using a patch containing vaccine-coated microneedles could be an attractive approach to improve influenza vaccination compliance and efficacy.Solid microneedle arrays coated with inactivated influenza vaccine were prepared for simple vaccine delivery to the skin. However, the stability of the influenza vaccine, as measured by hemagglutination activity, was found to be significantly damaged during microneedle coating. The addition of trehalose to the microneedle coating formulation retained hemagglutination activity, indicating stabilization of the coated influenza vaccine. For both intramuscular and microneedle skin immunization, delivery of un-stabilized vaccine yielded weaker protective immune responses including viral neutralizing antibodies, protective efficacies, and recall immune responses to influenza virus. Immunization using un-stabilized vaccine also shifted the pattern of antibody isotypes compared to the stabilized vaccine. Importantly, a single microneedle-based vaccination using stabilized influenza vaccine was found to be superior to intramuscular immunization in controlling virus replication as well as in inducing rapid recall immune responses post challenge.The functional integrity of hemagglutinin is associated with inducing improved protective immunity against influenza. Simple microneedle influenza vaccination in the skin produced superior protection compared to conventional intramuscular immunization. This approach is likely to be applicable to other vaccines too.
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? ...
... 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 doctor...
MacLennan, Calman A.; Saul, Allan
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
MacLennan, Calman A; Saul, Allan
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.
Susan M Twine
Full Text Available Francisella tularensis subspecies tularensis is the causative agent of a spectrum of diseases collectively known as tularemia. An attenuated live vaccine strain (LVS has been shown to be efficacious in humans, but safety concerns have prevented its licensure by the FDA. Recently, F. tularensis LVS has been produced under Current Good Manufacturing Practice (CGMP guidelines. Little is known about the immunogenicity of this new vaccine preparation in comparison with extensive studies conducted with laboratory passaged strains of LVS. Thus, the aim of the current work was to evaluate the repertoire of antibodies produced in mouse strains vaccinated with the new LVS vaccine preparation.In the current study, we used an immunoproteomics approach to examine the repertoire of antibodies induced following successful immunization of BALB/c versus unsuccessful vaccination of C57BL/6 mice with the new preparation of F. tularensis LVS. Successful vaccination of BALB/c mice elicited antibodies to nine identified proteins that were not recognized by antisera from vaccinated but unprotected C57BL/6 mice. In addition, the CGMP formulation of LVS stimulated a greater repertoire of antibodies following vaccination compared to vaccination with laboratory passaged ATCC LVS strain. A total of 15 immunoreactive proteins were identified in both studies, however, 16 immunoreactive proteins were uniquely reactive with sera from the new formulation of LVS.This is the first report characterising the antibody based immune response of the new formulation of LVS in the widely used murine model of tularemia. Using two mouse strains, we show that successfully vaccinated mice can be distinguished from unsuccessfully vaccinated mice based upon the repertoire of antibodies generated. This opens the door towards downselection of antigens for incorporation into tularemia subunit vaccines. In addition, this work also highlights differences in the humoral immune response to
Jacobson, Sheldon H; Sewell, Edward C; Proano, Ruben A
In 2002, several factors resulted in pediatric vaccine manufacturers not being able to produce a sufficient number of vaccines to vaccinate all the children in the United States according to the Recommended Childhood Immunization Schedule. The resulting vaccine supply shortage resulted in thousands of children not being fully immunized according to this schedule, and hence, created an unnecessary risk for epidemic outbreaks of several childhood diseases. The Centers for Disease Control and Prevention responded to this crisis by using pediatric vaccine stockpiles to mitigate the impact of future shortages. This paper presents a stochastic model that captures the vaccine supply during production interruptions. This model is used to assess the impact of pediatric vaccine stockpile levels on vaccination coverage rates, by considering the probability that all children can be immunized according to the Recommended Childhood Immunization Schedule over a given time period and the expected minimum vaccine supply. The model is also used to assess the proposed pediatric vaccine stockpile levels recommended by the United States Department of Health and Human Services. The results of this analysis suggest that the proposed vaccine stockpile levels are adequate to meet future vaccine production interruptions, provided that such production interruptions do not last more than six months (which is not surprising, given that is the time period for which they were designed). However, given that recent vaccine production interruptions have lasted (on average) for over one year, the proposed vaccine stockpile levels are insufficient to meet the nation's pediatric immunization needs during such time periods, which in turn could lead to localized and/or widespread disease outbreaks. Moreover, a moderate investment in higher vaccine stockpile levels would lead to a significantly reduced risk of such events.
Suckow, Mark A; Haab, Rudolph W; Miloscio, Lawrence J; Guilloud, Norman B
Pasteurella multocida is a bacterial pathogen that can cause significant disease and subsequent effects on research activities involving rabbits. Although several vaccines have been tested under laboratory conditions, field trials of vaccines for the control of P. multocida in rabbits are few. We used a potassium thiocyanate extract (PTE) produced from P. multocida serotype D:3,12,15 to vaccinate Pasteurella-free rabbits at their introduction into a colony having endemic infection with P. mul...
Full Text Available Most of the cases of vaccine associated myocarditis have been following small pox vaccination. Reports have also been there after streptococcal pneumonia vaccine and influenza vaccine. In some cases, autoimmune/inflammatory syndrome induced by adjuvants (ASIA used in the vaccine have been implicated. Exclusion of other causes is very important in the diagnostic process, especially that of acute coronary syndrome. Management is similar to that of other etiologies of myocarditis. These rare instances of myocarditis should not preclude one from taking necessary immunization for vaccine preventable diseases.
Hogue, Michael D; Meador, Anna E
Vaccines are among most cost-effective public health strategies. Despite effective vaccines for many bacterial and viral illnesses, tens of thousands of adults and hundreds of children die each year in the United States from vaccine-preventable diseases. Underutilization of vaccines requires rethinking the approach to incorporating vaccines into practice. Arguably, immunizations could be a part all health care encounters. Shared responsibility is paramount if deaths are to be reduced. This article reviews the available vaccines in the US market, as well as practice recommendations of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. Copyright © 2016 Elsevier Inc. All rights reserved.
Gupta, Gaurav; Giannino, Viviana; Rishi, Narayan; Glueck, Reinhard
Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver. The goal of this study was to develop an alternate potent HPV recombinant L1-based vaccines by producing HPV virus-like particles into a vaccine that is currently used worldwide. Live attenuated measles virus (MV) vaccines have a well-established safety and efficacy record, and recombinant MV (rMV) produced by reverse genetics may be useful for generating candidate HPV vaccines to meet the needs of the developing world. We studied in non-human primate rMV-vectored HPV vaccine in parallel with a classical alum adjuvant recombinant HPV16L1 and 18L1 protein vaccine produced in Pichia pastoris. A combined prime-boost approach using both vaccines was evaluated, as well as immune interference due to pre-existing immunity against the MV. The humoral immune response induced by the MV, Pichia-expressed vaccine, and their combination as priming and boosting approaches was found to elicit HPV16L1 and 18L1 specific total IgG and neutralizing antibody titres. Pre-existing antibodies against measles did not prevent the immune response against HPV16L1 and 18L1. Copyright © 2016 Elsevier Ltd. All rights reserved.
Nusbaum, Kenneth E; Wright, James C; Johnston, William B; Allison, Andrew B; Hilton, Clayton D; Staggs, Lydia A; Stallknecht, David E; Shelnutt, Joseph L
Sixteen Chilean flamingos, Phoenicopterus chiles, and 10 red-tailed hawks, Buteo jamacensis, were vaccinated in the pectoral muscle with 0.2 ml of a commercially produced killed West Nile virus vaccine intended for use in horses. Half the birds of each species received a booster vaccination 3 weeks after the first injection. Three weeks after the booster vaccination, none of 13 birds surveyed had detectable antibody to West Nile virus.
containing 50gmL−1 each of neomycin and streptomycin and supplemented with 0.5% human serum albumin , U.S.P. The lyophilized vaccine is the filtered...vaccine was prepared from specific pathogen-free eggs infected with the attenuated CM4884 strain of WEE virus. The supernatant was harvested and filtered...supernatant harvested from primary chicken embryo cell cultures. The vaccine was prepared from spe- cific pathogen-free eggs infected with the
Ward, Richard L; McNeal, Monica M; Steele, A Duncan
A "Meeting on Upstream Rotavirus Vaccines and Emerging Vaccine Producers" was held at the World Health Organization in Geneva, Switzerland on March 28-30, 2006. The purpose was to discuss, evaluate, and weigh the importance of additional rotavirus vaccine candidates following the successful international licensure of rotavirus vaccines by two major pharmaceutical companies (GlaxoSmithKline and Merck) that had been in development for many years. Both licensed vaccines are composed of live rotaviruses that are delivered orally as have been all candidate rotavirus vaccines evaluated in humans. Each is built on the experience gained with previous candidates whose development had either been discontinued or, in the case of the previously licensed rhesus rotavirus reassortant vaccine (Rotashield), was withdrawn by its manufacturer after the discovery of a rare association with intussusception. Although which alternative candidate vaccines should be supported for development and where this should be done are controversial topics, there was general agreement expressed at the Geneva meeting that further development of alternative candidates is a high priority. This development will help insure that the most safe, effective and economic vaccines are available to children in Third World nations where the vast majority of the >600,000 deaths due to rotavirus occur each year. This review is intended to provide the history and present status of rotavirus vaccines as well as a perspective on the future development of candidate vaccines as a means of promulgating plans suggested at the Geneva meeting.
Amorij, J-P.; Saluja, V.; Petersen, A.H.; Hinrichs, W.L.J.; Huckriede, A.; Frijlink, H.W.
In this study pulmonary vaccination with a new influenza subunit vaccine powder was evaluated. Vaccine powder was produced by spray-freeze drying (SFD) using the oligosaccharide inulin as stabilizer. Immune responses after pulmonary vaccination of BALB/c mice with vaccine powder were determined and
For many, an AIDS vaccine holds the promise of intervening in a widespread epidemic because it is not predicated on changing economic structures and social contexts underlying vulnerability to HIV for millions of individuals. Yet 20 years into the AIDS epidemic, there is still no vaccine. Based on interviews of AIDS vaccine researchers, watchdog organizations, and ethics groups from the United States, South Africa, and Kenya conducted between August and December of 2003, this paper explores possible answers to the question of why there is no vaccine, looking in particular at contradictions between a biomedical research industry increasingly driven by market incentives and a disease that primarily affects individuals living in low-income countries with little vaccine purchasing power. Producing a vaccine that could be effective in low-income regions requires new kinds of initiatives that can coordinate research nationally and globally, and circumvent current regulatory mechanisms that dictate against the development and dissemination of low-profit medical technologies. Until such initiatives are supported, however, vaccine research will continue at a devastatingly slow pace at the cost of millions of lives annually.
Previously reported data on the pathogenesis and immunogenicity of live vaccine strain LVS have been sufficiently encouraging to warrant an...potential for oral immunization with live tularemia vaccine prepared from strain LVS.
The Vaccine Safety Datalink is part of the National Immunization Program within the Centers for Disease Control and Prevention and was started in recognition of gaps in the scientific knowledge of rare vaccine side effects.
.... Whether a vaccine's target is naturally occurring or present because of hostile intent, the issues policy makers must deal with include vaccine development, production, availability, safety, effectiveness, and access...
Since last year, it has become possible to vaccinate against the human papillomavirus (HPV) that causes most cases of cervical cancer, but countries face tough decisions before making the vaccine widely available.
Morton, D B
Vaccination promotes animal welfare by protecting animal health, but it also has other welfare benefits, e.g. recent investigations have looked at the potential of vaccines in immunoneutering such as immunocastration--a humane alternative to the painful traditional methods. Similarly, vaccination can be used during disease outbreaks as a viable alternative to stamping-out, thus avoiding the welfare problems that on-farm mass slaughter can cause. Protecting animal health through vaccination leads to improved animal welfare, and maintaining good welfare ensures that animals can respond successfully to vaccination (as poor welfare can lead to immunosuppression, which can affect the response to vaccination). It is clear that vaccination has tremendous advantages for animal welfare and although the possible side effects of vaccination can have a negative effect on the welfare of some individual animals, the harm caused by these unwanted effects must be weighed against the undoubted benefits for groups of animals.
... before I knew I was pregnant? Will this harm my baby? Probably not. The chance of the ... pertussis-tdap-vaccine-pregnancy/pdf/ . The need for vaccination for other diseases during pregnancy will vary and ...
... medicines and vaccines. There is no evidence of harm caused by the low doses of thimerosal in ... and is therefore less likely to cause any harm. Thimerosal prevents the growth of bacteria in vaccines. ...
Following the release of a consensus statement from the NCI-Designated Cancer Centers urging HPV vaccination in the United States, Dr. Noel Brewer discusses the country’s low vaccination rates and how clinicians can help to improve them.
... Global Map Premature Birth Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal ... Pregnancy > Prenatal care > Vaccinations and pregnancy Vaccinations and pregnancy E-mail to a friend Please fill in ...
... vaccines. Vaccine-preventable diseases have many social and economic costs: sick children miss school and can cause ... there are only a few cases of disease today, if we take away the protection given by ...
Williamson, Eric M L; Chahin, Salim; Berger, Joseph R
Vaccinations help prevent communicable disease. To be valuable, a vaccine's ability to prevent disease must exceed the risk of adverse effects from administration. Many vaccines present no risk of infection as they are comprised of killed or non-infectious components while other vaccines consist of live attenuated microorganisms which carry a potential risk of infection-particularly, in patients with compromised immunity. There are several unique considerations with respect to vaccination in the multiple sclerosis (MS) population. First, there has been concern that vaccination may trigger or aggravate the disease. Second, disease-modifying therapies (DMTs) employed in the treatment of MS may increase the risk of infectious complications from vaccines or alter their efficacy. Lastly, in some cases, vaccination strategies may be part of the treatment paradigm in attempts to avoid complications of therapy.
... Term Complications of Diabetes Your Child's Immunizations: Pneumococcal Vaccines (PCV, PPSV) KidsHealth > For Parents > Your Child's Immunizations: ... or HIV infection); or cochlear implants. Why the Vaccines Are Recommended Children younger than 2 years old, ...
Chand, Puran; Chhabra, Rajesh; Nagra, Juhi
Bovine brucellosis is an economically important disease which seriously affects dairy farming by causing colossal losses. It can be controlled by practicing vaccination of animals with Brucella abortus S19 vaccine (S19 vaccine). In the present study, adult bovines were vaccinated on seven dairy farms with a reduced dose of S19 vaccine to control brucellosis. Serological screening of adult animals (N = 1,082) by Rose Bengal test (RBT) and ELISA prior to vaccination revealed the presence and absence of brucellosis on five and two farms, respectively. The positive animals (N = 171) were segregated and those which tested negative (N = 911) were vaccinated by conjunctival route with a booster after 4 months. The conjunctival vaccination induced weak antibody response in animals, which vanished within a period of 9 to 12 weeks. Abortion in 12 animals at various stages of pregnancy and post-vaccination was recorded, but none was attributed to S19 vaccine. However, virulent B. abortus was incriminated in six heifers, and the cause of abortion could not be established in six animals. The six aborted heifers perhaps acquired infection through in utero transmission or from the environment which remained undetected until abortion. These findings suggested that vaccination of adult animals with a reduced dose of S19 vaccine by conjunctival route did not produce adverse effects like abortion in pregnant animals and persistent vaccinal antibody titers, which are the major disadvantages of subcutaneous vaccination of adult animals.
Stephenson, J R
Vaccination has been one of the most successful and cost-effective health interventions ever employed. One disease (smallpox) has been eradicated, another (poliomyelitis) should disappear early in the new millennium and a third (measles) should follow shortly after. Conventional vaccines usually depend on one of three development processes, attenuation of virulent organisms (by passage in cell culture and/or experimental animals), killing of virulent organisms (by chemical inactivation) or the purification of immunogenic molecules (either proteins or carbohydrates) from whole organisms. These traditional processes, although serendipitous and poorly understood, have produced effective pharmaceutical products which give excellent protection against diseases such as smallpox, rabies, measles, yellow fever, tetanus and diphtheria. In spite of these successes however, the application of these protocols have failed to produce safe and efficacious vaccines against other infectious diseases which kill or maim tens of millions of people every year. The most important of these are malaria, AIDS, herpes, dengue fever and some forms of viral hepatitis. Consequently, fundamentally new technologies are required to tackle these important infections. One of the most promising has been the development of genetically modified viruses. This process normally involves taking a proven safe and efficacious vaccine virus, such as vaccinia or adenovirus, and modifying its genome to include genes coding for immunogenic proteins from other viruses such as HIV or measles. This review will describe the generation of such novel vaccine vectors and compare their advantages and shortcomings. In addition the literature describing their use as experimental vaccines will also be reviewed.
Otrashevskaia, E V; Kulak, M V; Otrashevskaia, A V; Karpov, I A; Fisenko, E G; Ignat'ev, G M
In this work we report the mumps vaccine virus shedding based on the laboratory confirmed cases of the mumps virus (MuV) infection. The likely epidemiological sources of the transmitted mumps virus were children who were recently vaccinated with the mumps vaccine containing Leningrad-Zagreb or Leningrad-3 MuV. The etiology of the described cases of the horizontal transmission of both mumps vaccine viruses was confirmed by PCR with the sequential restriction analysis.
Clarke, Steve; Giubilini, Alberto; Walker, Mary Jean
ABSTRACT Vaccine refusal occurs for a variety of reasons. In this article we examine vaccine refusals that are made on conscientious grounds; that is, for religious, moral, or philosophical reasons. We focus on two questions: first, whether people should be entitled to conscientiously object to vaccination against contagious diseases (either for themselves or for their children); second, if so, to what constraints or requirements should conscientious objection (CO) to vaccination be subject. ...
Midthun, K; Kapikian, A Z
Rotavirus vaccine development has focused on the delivery of live attenuated rotavirus strains by the oral route. The initial "Jennerian" approach involving bovine (RIT4237, WC3) or rhesus (RRV) rotavirus vaccine candidates showed that these vaccines were safe, well tolerated, and immunogenic but induced highly variable rates of protection against rotavirus diarrhea. The goal of a rotavirus vaccine is to prevent severe illness that can lead to dehydration in infants and young children in both...
McNeil, Michael M; DeStefano, Frank
Vaccine-associated hypersensitivity reactions are not infrequent; however, serious acute-onset, presumably IgE-mediated or IgG and complement-mediated anaphylactic or serious delayed-onset T cell-mediated systemic reactions are considered extremely rare. Hypersensitivity can occur because of either the active vaccine component (antigen) or one of the other components. Postvaccination acute-onset hypersensitivity reactions include self-limited localized adverse events and, rarely, systemic reactions ranging from urticaria/angioedema to full-blown anaphylaxis with multisystem involvement. Risk of anaphylaxis after all vaccines is estimated to be 1.31 (95% CI, 0.90-1.84) per million vaccine doses, respectively. Serious hypersensitivity reactions after influenza vaccines are particularly important because of the large number of persons vaccinated annually. Influenza vaccines are unique in requiring annual changes in the vaccines' antigenic composition to match the predicted circulating influenza strains. Recently, novel influenza vaccine types were introduced in the United States (recombinant vaccines, some with higher antigen content and a new adjuvanted vaccine). Providers should be aware of changing recommendations on the basis of recent published evidence for persons with a history of egg allergy to receive annual influenza vaccination. Further research is needed to elucidate the pathophysiology and risk factors for reported vaccine-associated adverse events. Further research is also needed to determine whether repeated annual inactivated influenza vaccination, the number of vaccine antigens administered at the same time, and the current timing of routine infant vaccinations are optimal for overall population well-being. Published by Elsevier Inc.
Zhang, Wangqian; Wang, Shuning; Gu, Jintao; Gao, Yuan; Wang, Zhaowei; Zhang, Kuo; Mu, Nan; Huang, Tonglie; Li, Weina; Hao, Qiang; Xue, Xiaochang; Zhang, Wei; Zhang, Yingqi; Zhang, Cun
Immunotherapy is gathering momentum as a kind of important therapy for cancer patients. However, monotherapies have limited efficacy in improving outcomes and benefit only in a small subset of patients. Combination therapies targeting multiple pathways often can augment an immune response to improve survival further. Here, the tumoricidal effects of the dual hPD-L1(human programmed cell death ligand 1) vaccination/HER2(human epidermal growth factor receptor 2) gene vaccination immunotherapy against the established HER2-expressed cancers were observed. Animals treated with combination therapy using hPD-L1 vaccine and HER2 gene vaccine had significantly improved survival in a mammary carcinoma model. We observed an increase in tumor growth inhibition following treatment. The percentage of the tumor-free mice (%) was much higher in the combined PD-L1/HER2 group. Furthermore, under the tumor-burden condition, hPD-L1 vaccine enhanced humoral immunity of HER2 gene vaccine. And the combination treatment increased the IFN-γ-producing effector T cells. Additionally, splenocytes from the combined PD-L1/HER2 group immunized mice possessed higher CTL activity. Notably, vaccination with combination therapy induced a significant decrease in the percentage of CD4 + CD25 + Treg cells. Collectively, these data demonstrate that PD-L1/HER2 gene vaccine combination therapy synergistically generates marked tumoricidal effects against established HER2-expressing cancers. Copyright © 2018 Elsevier Inc. All rights reserved.
Kamstrup, Søren; Roensholt, L.; Jensen, M.Holm
by Vaccination of the dam. We describe in this report the production and initial testing of an inactivated subunit vaccine against BVDV. The vaccine is based on production of antigen in primary bovine cell cultures, extraction of antigens from infected cells with detergent, chromatographic purification......, concentration, and insertion of antigens into immune stimulating complexes (ISCOMs). Vaccines based on two different Danish strains of BVDV were injected into calves and the antisera produced were tested for neutralising activity against a panel of Danish BVDV strains. The two vaccines induced different...... neutralisation responses, which seem to partly complement each other. The implication of these observations for successful Vaccination against BVDV is discussed....
Bogacheva, N V; Darmov, I V; Borisevich, I V; Kriuchkov, A V; Pechenkin, D V
The study of the time course of changes in cell immunological parameters by a magnetic separation technique in human beings during the administration of plague vaccine in relation to the immunological load revealed the higher blood levels of all T lymphocyte subpopulations on day 14 after vaccination. These changes are most typical of a primary vaccinated cohort. The increased frequency of plague vaccine administration and multiple immunizations with live plague, anthrax, and tularemia vaccines produce the time-course of changes in T lymphocyte populations (subpopulations) in response to the regular administration of plague vaccine. A high immunological load in man also promotes a significant reduction in the level of B lymphocytes.
... Animal and Plant Health Inspection Service Oral Rabies Vaccine Trial; Availability of a Risk Assessment... prepared to assess the risks associated with an experimental rabies vaccine, analyzes the use of that... evaluate a wildlife rabies vaccine that will produce sufficient levels of population immunity in raccoons...
... and Plant Health Inspection Service [Docket No. APHIS-2013-0046] Oral Rabies Vaccine Trial... whether the wildlife rabies vaccine will produce sufficient levels of population immunity against raccoon... rabies. The ORV program has utilized a vaccinia-rabies glycoprotein (V-RG) vaccine. APHIS-WS' use of the...
The current paradigm in vaccine lot release testing is that each final lot of vaccine produced is unique, due to the considerable inherent variation in the preceding biological production process. Consequently, each individual vaccine lot needs to be tested for safety and potency, frequently
The eradication of smallpox, one of the great triumphs of medicine, was accomplished through the prophylactic administration of live vaccinia virus, a comparatively benign relative of variola virus, the causative agent of smallpox. Nevertheless, recent fears that variola virus may be used as a biological weapon together with the present susceptibility of unimmunized populations have spurred the development of new-generation vaccines that are safer than the original and can be produced by modern methods. Predicting the efficacy of such vaccines in the absence of human smallpox, however, depends on understanding the correlates of protection. This review outlines the biology of poxviruses with particular relevance to vaccine development, describes protein targets of humoral and cellular immunity, compares animal models of orthopoxvirus disease with human smallpox, and considers the status of second- and third-generation smallpox vaccines. Published 2010. This article is a US Government work and is in the public domain in the USA.
Heppell, Joël; Lorenzen, Niels; Armstrong, Neil K.
Disease control is one of the major concerns in the aquaculture industry. However, there are no vaccines available for the prevention of many piscine infectious diseases, especially those of viral and parasitic origin. DNA-based vaccination could circumvent several problems associated...... no permanent tissue damage. To further investigate the ability of DNA-based vaccines to induce protective immunity in fish, viral haemorrhagic septicaemia virus G and N genes were cloned individually into an expression plasmid. Both G and N proteins produced in transfected fish cells appeared identical...... protein, killing the transfected host cells and ablating further expression of G protein and luciferase. Finally, young rainbow trout injected with the G construct, alone or together with the N construct, were strongly protected against challenge with live virus. These results suggest that DNA vaccines...
Development of a Subunit Vaccine for Contagious Bovine Pleuropneumonia in Africa (CIFSRF Phase 2). This project will allow researchers from Canada and Kenya to field trial a vaccine for contagious bovine pleuropneumonia. This endemic livestock disease affects the livelihoods of more than 24 million cattle producers ...
This project will allow researchers from Canada and Kenya to field trial a vaccine for contagious bovine pleuropneumonia. This endemic livestock disease affects the livelihoods of more than 24 million cattle producers and results in annual losses estimated at US$1 billion across sub-Saharan Africa. About the vaccine Using ...
Bosch, H.J.; Schots, A.
Plants are an attractive platform for the production of N-glycosylated subunit vaccines. Wild type glycosylation of plants can be exploited to produce vaccines that antigen-presenting cells effectively take up, degrade and present to cells of the adaptive immune system. Alternatively,
Hikke, Mia C.; Pijlman, Gorben P.
Vaccination is essential in livestock farming and in companion animal ownership. Nucleic acid vaccines based on DNA or RNA provide an elegant alternative to those classical veterinary vaccines that have performed suboptimally. Recent advances in terms of rational design, safety, and efficacy have
Holmgren, Jan; Svennerholm, Ann-Mari
There remains a great need to develop vaccines against many of the pathogens that infect mucosal tissues or have a mucosal port of entry. Parenteral vaccination may protect in some instances, but usually a mucosal vaccination route is necessary. Mucosal vaccines also have logistic advantages over injectable vaccines by being easier to administer, having less risk of transmitting infections and potentially being easier to manufacture. Still, however, only relatively few vaccines for human use are available: oral vaccines against cholera, typhoid, polio, and rotavirus, and a nasal vaccine against influenza. For polio, typhoid and influenza, in which the pathogens reach the blood stream, there is also an injectable vaccine alternative. A problem with available oral live vaccines is their reduced immunogenicity when used in developing countries; for instance, the efficacy of rotavirus vaccines correlates closely with the national per capita income. Research is needed to define the impact of factors such as malnutrition, aberrant intestinal microflora, concomitant infections, and preexisting immunity as well as of host genetic factors on the immunogenicity of these vaccines. Copyright © 2012 Elsevier Ltd. All rights reserved.
Rombout, J.H.W.M.; Kiron, V.
Among the novel vaccination methods, mucosal vaccination seems to possess all the desired criteria. The chapter reviews the state-of-the-art knowledge regarding this type of vaccination with a focus on their uptake, immune stimulation, and where possible, discusses their potential as future
... can also ask your doctor to record the vaccines your child has received in your state’s immunization registry. Just ... Talk to your child’s doctor to determine what vaccines your child needs for protection against vaccine preventable diseases. Immunization ...
Embregts, Carmen W.E.; Forlenza, Maria
The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen
S. M. Kharit
Full Text Available Massive vaccination had proved its effective morbidity reduction. Today it is necessary to extend vaccination schedule, creation of selective, regional schedules based on epidemiological, clinical, economical substantiation. Development of vaccination needs the profound scientific research, modernization of adverse reaction observing system, betterment training system and awareness of population.
Process flow diagram for producing biological product . 1 frozen vial .Setup2 flasks .SetupB flasks o Master Cell Bank . lrradiation E@E n ffi IilIE¡EEI...and flow diagram of the manufacturing procedure is shown. Total of 50 vaccine vials was produced as well as master cell bank that can be used for future... membrane antigen 1 (PfAMA-1) and with gp96-Ig and generated vaccine cells line 293-gp96-lgPrAMAl-PrcsP. Our immunogenicity studies in mice were designed to
Parrino, Janie; Graham, Barney S
The global eradication of smallpox was a tremendous achievement made possible by the development of an effective vaccine. Routine vaccination of the general population is no longer recommended. However, stocks of variola virus, the causative agent of smallpox, still exist in 2 secure laboratories, and permanent disposal has been controversial. In addition, there is speculation that variola virus may exist outside of these 2 facilities, and there is a concern that the threat of smallpox will be used as a bioterrorist weapon. In 2002, this concern led to a vaccination campaign in US military and civilian healthcare workers and first responders. Although the historical live virus vaccine has proven efficacy, it also is associated with serious adverse events and rare fatal reactions, particularly in the setting of immunodeficiency and atopic eczema. In addition, this vaccine was historically produced using animal intermediaries in a process that was prone to contamination and not acceptable for current manufacturing standards. Development of alternative poxvirus vaccines is focused on replication-defective viruses, gene-based vectors, and subunit approaches to improve safety and immunogenicity. The conundrum is that in the absence of an intentional release of variola, efficacy evaluation of new candidate vaccines will be limited to animal model testing, which creates new challenges for the vaccine licensure process. Although motivated by the threat of bioterrorism, the hope is for new poxvirus vaccines to have their greatest utility against other pathogenic orthopoxviruses such as monkeypox and for the development of recombinant poxvirus-based vectors to treat and prevent other diseases.
Larocca, Rafael A; Abbink, Peter; Peron, Jean Pierre S; Zanotto, Paolo M de A; Iampietro, M Justin; Badamchi-Zadeh, Alexander; Boyd, Michael; Ng'ang'a, David; Kirilova, Marinela; Nityanandam, Ramya; Mercado, Noe B; Li, Zhenfeng; Moseley, Edward T; Bricault, Christine A; Borducchi, Erica N; Giglio, Patricia B; Jetton, David; Neubauer, George; Nkolola, Joseph P; Maxfield, Lori F; De La Barrera, Rafael A; Jarman, Richard G; Eckels, Kenneth H; Michael, Nelson L; Thomas, Stephen J; Barouch, Dan H
Zika virus (ZIKV) is a flavivirus that is responsible for the current epidemic in Brazil and the Americas. ZIKV has been causally associated with fetal microcephaly, intrauterine growth restriction, and other birth defects in both humans and mice. The rapid development of a safe and effective ZIKV vaccine is a global health priority, but very little is currently known about ZIKV immunology and mechanisms of immune protection. Here we show that a single immunization with a plasmid DNA vaccine or a purified inactivated virus vaccine provides complete protection in susceptible mice against challenge with a strain of ZIKV involved in the outbreak in northeast Brazil. This ZIKV strain has recently been shown to cross the placenta and to induce fetal microcephaly and other congenital malformations in mice. We produced DNA vaccines expressing ZIKV pre-membrane and envelope (prM-Env), as well as a series of deletion mutants. The prM-Env DNA vaccine, but not the deletion mutants, afforded complete protection against ZIKV, as measured by absence of detectable viraemia following challenge, and protective efficacy correlated with Env-specific antibody titers. Adoptive transfer of purified IgG from vaccinated mice conferred passive protection, and depletion of CD4 and CD8 T lymphocytes in vaccinated mice did not abrogate this protection. These data demonstrate that protection against ZIKV challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection. Our findings suggest that the development of a ZIKV vaccine for humans is likely to be achievable.
Outbreaks of yellow fever in recent years in the Americas have prompted concern about the possible urbanization of jungle fever. Vaccination, using the 17D strain of yellow fever virus, provides an effective, practical method of large scale protection against the disease. Because yellow fever can reappear in certain areas after a 2-year dormancy period, some countries maintain routine vaccination programs in areas where jungle yellow fever is endemic. The size of the endemic area (approximately half of South America), transportation and communication difficulties, and the inability to ensure a reliable cold chain are problems facing these programs. In addition, the problem of reaching dispersed and isolated populations has been addressed by the use of mobile teams, radio monitoring, and educational methods. During yellow fever outbreaks, many countries institute massive vaccination campaigns, targeted at temporary workers and migrants. Because epidemics in South America may involve extensive areas, these campaigns may not effectively address the problem. The ped-o-jet injector method, used in Brazil and Colombia, should be used in outbreak situations, as it is effective for large-scale vaccination. Vaccine by needle, suggested for maintenance programs, should be administered to those above 1 year of age. An efficient monitoring method to avoid revaccination, and to assess immunity, should be developed. The 17D strain produces seroconversion in 95% of recipients, and most is prepared in Brazil and Colombia. But, problems with storage methods, instability in seed lots, and difficulties in large-scale production were identified in 1981 by the Pan American Health Organization and WHO. The group recommended modernization of current production techniques and further research to develop a vaccine that could be produced in cell cultures. Brazil and Colombia have acted on these recommendations, modernizing vaccine production and researching thermostabilizing media for
McLeod, A; Rushton, J
This paper describes the steps that might be used in assessing the economic justification for using vaccination to control animal disease, and the way that vaccination is financed and administered. It describes decisions that have been taken with respect to preserving international trade, and issues related to protection of livelihoods. Regardless of the motivation for vaccination, its costs can usually be shared between the public and private sectors. Cost-effective vaccination requires methods of delivery to be adapted to livestock production systems. The paper concludes by suggesting questions around the use of vaccination that would merit further economic analysis.
Burke, Megan; Rowe, Theresa
Vaccines are important for preventing infections in adults aged ≥65 years. Older adults are at increased risk for complications from vaccine-preventable illnesses due to age-associated changes in immune function and chronic medical comorbidities. Vaccination rates for older adults remain low despite widely accepted practice guidelines. Recommended vaccinations for older adults include (1) influenza; (2) pneumococcal; (3) herpes zoster; (4) tetanus, diphtheria, pertussis; and (5) hepatitis B. Cost influences vaccination rates in older adults. Copyright © 2017 Elsevier Inc. All rights reserved.
Despite great public interest and desperate need, progress toward a viable human immunodeficiency virus (HIV) vaccine remains incredibly slow. Since Merck began its HIV vaccine research in 1985, the pharmaceutical company has yet to produce a vaccine capable of passing Phase II testing. Merck Laboratories President Peter S. Kim recently delivered a speech at Yale University that detailed his company’s previous attempts to create an HIV vaccine and outlined a possible strategy for the future. ...
Goto, Yasuyuki; Bhatia, Ajay; Raman, Vanitha S; Liang, Hong; Mohamath, Raodoh; Picone, Alessandro F; Vidal, Silvia E Z; Vedvick, Thomas S; Howard, Randall F; Reed, Steven G
A subunit vaccine using a defined antigen(s) may be one effective solution for controlling leishmaniasis. Because of genetic diversity in target populations, including both dogs and humans, a multiple-antigen vaccine will likely be essential. However, the cost of a vaccine to be used in developing countries must be considered. We describe herein a multiantigen vaccine candidate comprised of antigens known to be protective in animal models, including dogs, and to be recognized by humans immune to visceral leishmaniasis. The polyprotein (KSAC) formulated with monophosphoryl lipid A, a widely used adjuvant in human vaccines, was found to be immunogenic and capable of inducing protection against Leishmania infantum, responsible for human and canine visceral leishmaniasis, and against L. major, responsible for cutaneous leishmaniasis. The results demonstrate the feasibility of producing a practical, cost-effective leishmaniasis vaccine capable of protecting both humans and dogs against multiple Leishmania species.
Zhang, Nian-Zhang; Chen, Jia; Wang, Meng; Petersen, Eskild; Zhu, Xing-Quan
Toxoplasmosis caused by the protozoan Toxoplasma gondii is a major public health problem, infecting one-third of the world human beings, and leads to abortion in domestic animals. A vaccine strategy would be an ideal tool for improving disease control. Many efforts have been made to develop vaccines against T. gondii to reduce oocyst shedding in cats and tissue cyst formation in mammals over the last 20 years, but only a live-attenuated vaccine based on the S48 strain has been licensed for veterinary use. Here, the authors review the recent development of T. gondii vaccines in cats, food-producing animals and mice, and present its future perspectives. However, a single or only a few antigen candidates revealed by various experimental studies are limited by only eliciting partial protective immunity against T. gondii. Future studies of T. gondii vaccines should include as many CTL epitopes as the live attenuated vaccines.
Gari, Getachew; Abie, Getnet; Gizaw, Daniel; Wubete, Alehegn; Kidane, Membere; Asgedom, Hagos; Bayissa, Berecha; Ayelet, Gelagay; Oura, Christopher A L; Roger, Francois; Tuppurainen, Eeva S M
The safety, immunogenicity and efficacy of three commercially available vaccines against lumpy skin disease (LSD) in cattle have been evaluated using a combination of vaccine challenge experiments and the monitoring of immune responses in vaccinated animals in the field. The three vaccines evaluated in the study included two locally produced (Ethiopian) vaccines (lumpy skin disease virus (LSDV) Neethling and Kenyan sheep and goat pox (KSGP) O-180 strain vaccines) and a Gorgan goat pox (GTP) vaccine manufactured by Jordan Bio-Industries Centre (JOVAC). The latter vaccine was evaluated for the first time in cattle against LSDV. The Ethiopian Neethling and KSGPO-180 vaccines failed to provide protection in cattle against LSDV, whereas the Gorgan GTP vaccine protected all the vaccinated calves from clinical signs of LSD. There was no significant difference in protective efficacy detected between two dosage levels (P=0.2, P=0.25, and P=0.1 for KSGP, Neethling and Gorgan vaccines, respectively). Additionally, the Gorgan GTP vaccinated cattle showed stronger levels of cellular immune responses measured using Delayed-Type Hypersensitivity (DTH) reactions at the vaccination site indicating higher levels of immunogenicity produced by the GTPV vaccine in cattle, as opposed to the other two vaccines. This study indicated, for the first time, that the Gorgan GTP vaccine can effectively protect cattle against LSDV and that the Neethling and KSGP O-180 vaccine were not protective. The results emphasise the need for molecular characterization of the Neethling and KSGP O-180 vaccine seed viruses used for vaccine production in Ethiopia. In addition, the potency and efficacy testing process of the Ethiopian LSD Neethling and KSGP O-180 vaccines should be re-evaluated. Copyright © 2015 Elsevier Ltd. All rights reserved.
He, Yongqun; Rappuoli, Rino; De Groot, Anne S.; Chen, Robert T.
Vaccine informatics is an emerging research area that focuses on development and applications of bioinformatics methods that can be used to facilitate every aspect of the preclinical, clinical, and postlicensure vaccine enterprises. Many immunoinformatics algorithms and resources have been developed to predict T- and B-cell immune epitopes for epitope vaccine development and protective immunity analysis. Vaccine protein candidates are predictable in silico from genome sequences using reverse vaccinology. Systematic transcriptomics and proteomics gene expression analyses facilitate rational vaccine design and identification of gene responses that are correlates of protection in vivo. Mathematical simulations have been used to model host-pathogen interactions and improve vaccine production and vaccination protocols. Computational methods have also been used for development of immunization registries or immunization information systems, assessment of vaccine safety and efficacy, and immunization modeling. Computational literature mining and databases effectively process, mine, and store large amounts of vaccine literature and data. Vaccine Ontology (VO) has been initiated to integrate various vaccine data and support automated reasoning. PMID:21772787
Geier, M R; Stanbro, H; Merril, C R
Twenty samples of commercial vaccines intended for administration to humans were assayed for the presence of bacterial endotoxins by using the Limulus amebocyte lysate test. Sixteen of the vaccines contained more than 0.1 ng of endotoxin per ml (which corresponds to 103 bacterial cell wall equivalents per ml in the undiluted vaccines). These results suggest that at some stage of preparation, the vaccines have contained varying amounts of gram-negative bacteria and may indicate the presence of other bacterial products as well. It might be useful to list the level of endotoxins, phage, and other contaminants on each vaccine lot to facilitate studies on any side effects of these contaminants. Selection of vaccine lots with the least endotoxin might reduce some of the adverse effects of vaccinations. PMID:727776
Mark V. Pauly
Full Text Available This paper explores the relationship between the research for and development of vaccines against global pandemics and insurance. It shows that development in advance of pandemics of a portfolio of effective and government-approved vaccines does have some insurance properties: it requires incurring costs that are certain (the costs of discovering, developing, and testing vaccines in return for protection against large losses (if a pandemic treatable with one of the vaccines occurs but also with the possibility of no benefit (from a vaccine against a disease that never reaches the pandemic stage. It then argues that insurance against the latter event might usefully be offered to organizations developing vaccines, and explores the benefits of insurance payments to or on behalf of countries who suffer from unpredictable pandemics. These ideas are then related to recent government, industry, and philanthropic efforts to develop better policies to make vaccines against pandemics available on a timely basis.
Rasmussen, Jesper Skou; Lorenzen, Ellen; Kjær, Torben Egil
Vaccine producers often recommend a minimum size of 5g for vaccination of rainbow trout, but implementation of prophylactic vaccination in smaller sized fish would be an advantage for several infectious diseases. To implement a cost efficient vaccination strategy, it is important to know the dura......Vaccine producers often recommend a minimum size of 5g for vaccination of rainbow trout, but implementation of prophylactic vaccination in smaller sized fish would be an advantage for several infectious diseases. To implement a cost efficient vaccination strategy, it is important to know...... the duration and nature of the protective immunity induced by the vaccines in the fish. The present work aimed at determination of the smallest size at which specific immunity could be induced in rainbow trout fry by DNA vaccination against viral haemorrhagic septicaemia (VHS). Earlier experiments revealed...... that intramuscular injection of the DNA vaccine encoding the viral glycoprotein G induced protective immunity to VHS in rainbow trout fry of 0.5g.However, the vaccine is known to induce both innate and adaptive protection. The present work therefore aimed at determination of which type of protection the DNA vaccine...
Hess, Jessica A; Zhan, Bin; Bonne-Année, Sandra; Deckman, Jessica M; Bottazzi, Maria Elena; Hotez, Peter J; Klei, Thomas R; Lustigman, Sara; Abraham, David
Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunisation protocol in mice. In addition, we tested the hypothesis that joining protective antigens as a fusion protein or in combination, into a multivalent vaccine, would improve the ability of the vaccine to induce protective immunity. Out of eight vaccine candidates tested in this study, Ov-103, Ov-RAL-2 and Ov-CPI-2M were shown to reproducibly induce protective immunity when administered individually, as fusion proteins or in combination. Although there was no increase in the level of protective immunity induced by combining the antigens into one vaccine, these antigens remain strong candidates for inclusion in a vaccine to control onchocerciasis in humans. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
Full Text Available Vaccines have significantly reduced the detrimental effects of numerous human infectious diseases worldwide, helped to reduce drastically child mortality rates and even achieved eradication of major pathogens, such as smallpox. These achievements have been possible due to a dedicated effort for vaccine research and development, as well as an effective transfer of these vaccines to public health care systems globally. Either public or private institutions have committed to developing and manufacturing vaccines for local or international population supply. However, current vaccine manufacturers worldwide might not be able to guarantee sufficient vaccine supplies for all nations when epidemics or pandemics events could take place. Currently, different countries produce their own vaccine supplies under Good Manufacturing Practices, which include the USA, Canada, China, India, some nations in Europe and South America, such as Germany, the Netherlands, Italy, France, Argentina, and Brazil, respectively. Here, we discuss some of the vaccine programs and manufacturing capacities, comparing the current models of vaccine management between industrialized and developing countries. Because local vaccine production undoubtedly provides significant benefits for the respective population, the manufacture capacity of these prophylactic products should be included in every country as a matter of national safety.
Rey-Jurado, Emma; Tapia, Felipe; Muñoz-Durango, Natalia; Lay, Margarita K; Carreño, Leandro J; Riedel, Claudia A; Bueno, Susan M; Genzel, Yvonne; Kalergis, Alexis M
Vaccines have significantly reduced the detrimental effects of numerous human infectious diseases worldwide, helped to reduce drastically child mortality rates and even achieved eradication of major pathogens, such as smallpox. These achievements have been possible due to a dedicated effort for vaccine research and development, as well as an effective transfer of these vaccines to public health care systems globally. Either public or private institutions have committed to developing and manufacturing vaccines for local or international population supply. However, current vaccine manufacturers worldwide might not be able to guarantee sufficient vaccine supplies for all nations when epidemics or pandemics events could take place. Currently, different countries produce their own vaccine supplies under Good Manufacturing Practices, which include the USA, Canada, China, India, some nations in Europe and South America, such as Germany, the Netherlands, Italy, France, Argentina, and Brazil, respectively. Here, we discuss some of the vaccine programs and manufacturing capacities, comparing the current models of vaccine management between industrialized and developing countries. Because local vaccine production undoubtedly provides significant benefits for the respective population, the manufacture capacity of these prophylactic products should be included in every country as a matter of national safety.
Wedlock, D N; Janssen, P H; Leahy, S C; Shu, D; Buddle, B M
Vaccination against rumen methanogens offers a practical approach to reduce methane emissions in livestock, particularly ruminants grazing on pasture. Although successful vaccination strategies have been reported for reducing the activity of the rumen-dwelling organism Streptococcus bovis in sheep and S. bovis and Lactobacillus spp. in cattle, earlier approaches using vaccines based on whole methanogen cells to reduce methane production in sheep have produced less promising results. An anti-methanogen vaccine will need to have broad specificity against methanogens commonly found in the rumen and induce antibody in saliva resulting in delivery of sufficiently high levels of antibodies to the rumen to reduce methanogen activity. Our approach has focussed on identifying surface and membrane-associated proteins that are conserved across a range of rumen methanogens. The identification of potential vaccine antigens has been assisted by recent advances in the knowledge of rumen methanogen genomes. Methanogen surface proteins have been shown to be immunogenic in ruminants and vaccination of sheep with these proteins induced specific antibody responses in saliva and rumen contents. Current studies are directed towards identifying key candidate antigens and investigating the level and types of salivary antibodies produced in sheep and cattle vaccinated with methanogen proteins, stability of antibodies in the rumen and their impact on rumen microbial populations. In addition, there is a need to identify adjuvants that stimulate high levels of salivary antibody and are suitable for formulating with protein antigens to produce a low-cost and effective vaccine.
Wang, Jing; Luo, FengJi; Feng, ZiJian; Li, Li; Bai, YunHua; Ai, Xing; Ma, JianXin; Zhang, Zheng; Shi, NianMin
Two kinds of regimens (2-1-1 and 1-1-1-1-1) can be selected after Zagreb regimen(2-1-1)of PVRV was officially approved in Beijing in January 2015. Up to now, the subjects for most studies about the comparison between Zagreb and Essen regimen are under 50 y old, rarely at and above. Aging of the immune system may result in decreasing efficacy of vaccination, especially for adults aged above 65-70 y. This study compared the safety and immunogenicity of the Zagreb and Essen regimen in Chinese adults aged 50 and above with the goal to provide a supplemental data for this age group. A total of 114 cases were divided into 2 groups randomly, received PVRV under the Zagreb and Essen regimens respectively. Serum samples were collected at D0, D7, D14, D42, D180 and D365 to determine the rabies serum neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT). Safety analyses were made by comparing the AEs in day-3, day-7, and day-(7 + 21) in Zagreb or day-(7 + 28) in Essen by gender and age cohorts. 617 blood samples were obtained. Two groups showed similar immunogenicity, the neutralizing antibody titer of all subjects at D14 and D42 showed >0.5 IU/ml. Under the same regimen, Subjects ≥65 y had lower GMC than those who <65 years from D7 to D365 within 2 groups. This difference was significantly shown on D7, D14, D180 in Zagreb group, and on D180 in Essen group (t = 2.38, p = 0.02; t = 3.78, p < 0.001; t = 2.30, p = 0.03; t = 4.42, p < 0.001). Subjects<65 years had higher seroconversion rate compared to ≥65 y on D7, D180 and D365 in both 2 groups, this difference was also significantly shown on D180, D365 in Zagreb group and on D180 in Essen group (χ 2 = 20.66, p < 0.001; χ 2 = 6.56, p = 0.02; χ 2 = 10.96, p = 0.002). Two regimens all showed favorable performances with mildly or common adverse events (AEs). The incidence of local AEs after 3 d in Essen group was higher than Zagreb group (χ 2 = 9.69, p = 0.002). The most common local AE was pain
Aubrit, Françoise; Perugi, Fabien; Léon, Arnaud; Guéhenneux, Fabienne; Champion-Arnaud, Patrick; Lahmar, Mehdi; Schwamborn, Klaus
Vaccines have been used for centuries to protect people and animals against infectious diseases. For vaccine production, it has become evident that cell culture technology can be considered as a key milestone and has been the result of decades of progress. The development and implementation of cell substrates have permitted massive and safe production of viral vaccines. The demand in new vaccines against emerging viral diseases, the increasing vaccine production volumes, and the stringent safety rules for manufacturing have made cell substrates mandatory viral vaccine producer factories. In this review, we focus on cell substrates for the production of vaccines against human viral diseases. Depending on the nature of the vaccine, choice of the cell substrate is critical. Each manufacturer intending to develop a new vaccine candidate should assess several cell substrates during the early development phase in order to select the most convenient for the application. First, as vaccine safety is quite naturally a central concern of Regulatory Agencies, the cell substrate has to answer the regulatory rules stringency. In addition, the cell substrate has to be competitive in terms of viral-specific production yields and manufacturing costs. No cell substrate, even the so-called "designer" cell lines, is able to fulfil all the requested criteria for all viral vaccines. Therefore, the availability of a variety of cell substrates for vaccine production is essential because it improves the chance to successfully respond to the current and future needs of vaccines linked to new emerging or re-emerging infectious diseases (e.g. pandemic flu, Ebola, and Chikungunya outbreaks). Copyright © 2015 Elsevier Ltd. All rights reserved.
Raida, Martin Kristian; Neumann, Lukas; Kragelund Strøm, Helene
A new biotype 2 of Y. ruckeri O1, which lacks motility has proven highly virulent for rainbow trout, and is causing disease in cultured trout even in fish vaccinated with commercial ERM biotype 1 vaccines. Not much is known about immunity against biotype 2, and therefore have we produced a Y....... ruckeri O1 biotype 2 immersion vaccine and tested the protection against both Y. ruckeri biotype 1 and 2 infections. Seven months post vaccination, both vaccinated and mock-vaccinated groups of rainbow trout were bath challenged with Y. ruckeri serotype O1, biotype 1 or 2. Challenge with biotype 2...... resulted in very low mortalities with no significant difference in mortality between vaccinated and mock-vaccinated fish. Challenge with biotype 1 resulted in a significantly lower mortality (P=0.0001) in the vaccinated group. This result was confirmed 15 months post vaccination (P
Thiomersal, also called thimerosal, is an ethyl mercury derivative used as a preservative to prevent bacterial contamination of multidose vaccine vials after they have been opened. Exposure to low doses of thiomersal has essentially been associated with hypersensitivity reactions. Nevertheless there is no evidence that allergy to thiomersal could be induced by thiomersal-containing vaccines. Allergy to thiomersal is usually of delayed-hypersensitivity type, but its detection through cutaneous tests is not very reliable. Hypersensitivity to thiomersal is not considered as a contraindication to the use of thiomersal-containing vaccines. In 1999 in the USA, thiomersal was present in approximately 30 different childhood vaccines, whereas there were only 2 in France. Although there were no evidence of neurological toxicity in infants related to the use of thiomersal-containing vaccines, the FDA considered that the cumulative dose of mercury received by young infants following vaccination was high enough (although lower than the FDA threshold for methyl mercury) to request vaccine manufacturers to remove thiomersal from vaccine formulations. Since 2002, all childhood vaccines used in Europe and the USA are thiomersal-free or contain only minute amounts of thiomersal. Recently published studies have shown that the mercury levels in the blood, faeces and urine of children who had received thiomersal-containing vaccines were much lower than those accepted by the American Environmental Protection Agency. It has also been demonstrated that the elimination of mercury in children was much faster than what was expected on the basis of studies conducted with methyl mercury originating from food. Recently, the hypothesis that mercury contained in vaccines could be the cause of autism and other neurological developmental disorders created a new debate in the medical community and the general public. To date, none of the epidemiological studies conducted in Europe and elsewhere
Hoenen, Thomas; Groseth, Allison; Feldmann, Heinz
Introduction Ebolaviruses cause severe viral hemorrhagic fever in humans and non-human primates, with case fatality rates of up to 90%. Currently, neither a specific treatment nor a vaccine licensed for use in humans is available. However, a number of vaccine candidates have been developed in the last decade that are highly protective in non-human primates, the gold standard animal model for Ebola hemorrhagic fever. Areas covered This review analyzes a number of scenarios for the use of ebolavirus vaccines, discusses the requirements for ebolavirus vaccines in these scenarios, and describes current ebolavirus vaccines. Among these vaccines are recombinant Adenoviruses, recombinant Vesicular Stomatitis viruses, recombinant Human Parainfluenza viruses and virus-like particles. Interestingly, one of these vaccine platforms, based on recombinant Vesicular Stomatitis viruses, has also demonstrated post-exposure protection in non-human primates. Expert opinion The most pressing remaining challenge is now to move these vaccine candidates forward into human trials and towards licensure. In order to achieve this, it will be necessary to establish the mechanisms and correlates of protection for these vaccines, and to continue to demonstrate their safety, particularly in potentially immunocompromised populations. However, already now there is sufficient evidence that, from a scientific perspective, a vaccine protective against ebolaviruses is possible. PMID:22559078
Smith, Jennifer C; Appleton, Mary; MacDonald, Noni E
Despite significant efforts by governments, organizations and individuals to maintain public trust in vaccines, concerns persist and threaten to undermine the effectiveness of immunization programs. Vaccine advocates have traditionally focused on education based on evidence to address vaccine concerns and hesitancy. However, being informed of the facts about immunization does not always translate into support for immunization. While many are persuaded by scientific evidence, others are more influenced by cognitive shortcuts, beliefs, societal pressure and the media, with the latter group more likely to hesitate over immunization. Understanding evidence from the behaviour sciences opens new doors to better support individual decision-making about immunization. Drawing on heuristics, this overview explores how individuals find, process and utilize vaccine information and the role health care professionals and society can play in vaccine decision-making. Traditional, evidence-based approaches aimed at staunching the erosion of public confidence in vaccines are proving inadequate and expensive. Enhancing public confidence in vaccines will be complex, necessitating a much wider range of strategies than currently used. Success will require a shift in how the public, health care professionals and media are informed and educated about vaccine benefits, risks and safety; considerable introspection and change in current academic and vaccine decision-making practices; development of proactive strategies to broadly address current and potential future concerns, as well as targeted interventions such as programs to address pain with immunization. This overview outlines ten such opportunities for change to improve vaccine confidence.
Full Text Available Abstract Background Conjugate vaccines in which polysaccharide antigens are covalently linked to carrier proteins belong to the most effective and safest vaccines against bacterial pathogens. State-of-the art production of conjugate vaccines using chemical methods is a laborious, multi-step process. In vivo enzymatic coupling using the general glycosylation pathway of Campylobacter jejuni in recombinant Escherichia coli has been suggested as a simpler method for producing conjugate vaccines. In this study we describe the in vivo biosynthesis of two novel conjugate vaccine candidates against Shigella dysenteriae type 1, an important bacterial pathogen causing severe gastro-intestinal disease states mainly in developing countries. Results Two different periplasmic carrier proteins, AcrA from C. jejuni and a toxoid form of Pseudomonas aeruginosa exotoxin were glycosylated with Shigella O antigens in E. coli. Starting from shake flask cultivation in standard complex medium a lab-scale fed-batch process was developed for glycoconjugate production. It was found that efficiency of glycosylation but not carrier protein expression was highly susceptible to the physiological state at induction. After induction glycoconjugates generally appeared later than unglycosylated carrier protein, suggesting that glycosylation was the rate-limiting step for synthesis of conjugate vaccines in E. coli. Glycoconjugate synthesis, in particular expression of oligosaccharyltransferase PglB, strongly inhibited growth of E. coli cells after induction, making it necessary to separate biomass growth and recombinant protein expression phases. With a simple pulse and linear feed strategy and the use of semi-defined glycerol medium, volumetric glycoconjugate yield was increased 30 to 50-fold. Conclusions The presented data demonstrate that glycosylated proteins can be produced in recombinant E. coli at a larger scale. The described methodologies constitute an important step
The Medical Service once again recommends you to get your annual flu vaccination for the year. Vaccination is the most effective way of avoiding the illness and any serious consequences and protecting those around you. The flu can have especially serious consequences for people with chronic conditions (diabetes, cardio-vascular disease, etc.), pregnant women, infants, and people over 65 years of age. Remember, anyone working on the CERN site who wishes to be vaccinated against seasonal flu should go to the Infirmary (Building 57, ground floor) with their vaccine. The Medical Service will issue a prescription on the day of the vaccination for the purposes of reimbursement by UNIQA. NB: The Medical Service cannot provide this vaccination service for family members or retired members of the personnel. For more information: • The "Seasonal flu" flyer by the Medical Service • Recommendations of the Swiss Federal Office of Public...
Full Text Available Active immunization of children has been proven very effective in elimination of life threatening complications of many infectious diseases in developed countries. However, as vaccination-preventable infectious diseases and their complications have become rare, the interest focuses on immunization-related adverse reactions. Unfortunately, fear of vaccination-related adverse effects can led to decreased vaccination coverage and subsequent epidemics of infectious diseases. This review includes reports about possible side effects following vaccinations in children with neurological disorders and also published recommendations about vaccinating children with neurological disorders. From all international published data anyone can conclude that vaccines are safer than ever before, but the challenge remains to convey this message to society.
Lithgow, Karen V; Cameron, Caroline E
Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a globally prevalent disease despite remaining susceptible to penicillin treatment. Syphilis vaccine development is a viable preventative approach that will serve to complement public health-oriented syphilis prevention, screening and treatment initiatives to deliver a two-pronged approach to stemming disease spread worldwide. Areas covered: This article provides an overview of the need for development of a syphilis vaccine, summarizes significant information that has been garnered from prior syphilis vaccine studies, discusses the critical aspects of infection that would have to be targeted by a syphilis vaccine, and presents the current understanding within the field of the correlates of protection needed to be achieved through vaccination. Expert commentary: Syphilis vaccine development should be considered a priority by industry, regulatory and funding agencies, and should be appropriately promoted and supported.
Esposito, Susanna; Bianchini, Sonia; Dellepiane, Rosa Maria; Principi, Nicola
The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.
Barraza, Leila; Schmit, Cason; Hoss, Aila
This paper discusses recent changes to state legal frameworks for mandatory vaccination in the context of school and healthcare worker vaccination. It then discusses state laws that allow pharmacists the authority to vaccinate.
Dudas, Robert A; Karron, Ruth A.
Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness (LRI) in infants and children worldwide and causes significant LRI in the elderly and in immunocompromised patients. The goal of RSV vaccination is to prevent serious RSV-associated LRI. There are several obstacles to the development of successful RSV vaccines, including the need to immunize very young infants, who may respond inadequately to vaccination; the existence of two antigenically d...
Nicol, A.F.; Andrade, C.V.; Russomano, F.B.; Rodrigues, L.L.S.; Oliveira, N.S.; D.W. Provance Jr
Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment o...
Full Text Available The development of synthetic peptide-based vaccines has many advantages in comparison with vaccines based on live attenuated organisms, inactivated or killed organism, or toxins. Peptide-based vaccines cannot revert to a virulent form, allow a better conservation, and are produced more easily and safely. However, they generate a weaker immune response than other vaccines, and the inclusion of adjuvants and/or the use of vaccine delivery systems is almost always needed. Among vaccine delivery systems, micro- and nanoparticulated ones are attractive, because their particulate nature can increase cross-presentation of the peptide. In addition, they can be passively or actively targeted to antigen presenting cells. Furthermore, particulate adjuvants are able to directly activate innate immune system in vivo. Here, we summarize micro- and nanoparticulated vaccine delivery systems used in the field of synthetic peptide-based vaccines as well as strategies to increase their immunogenicity.
Lindsay, William A; Wiedner, Ellen; Isaza, Ramiro; Townsend, Hugh G G; Boleslawski, Maria; Lunn, D P
Although captive elephants are commonly vaccinated annually against tetanus using commercially available tetanus toxoid vaccines marketed for use in horses and livestock, no data exists to prove that tetanus toxoid vaccination produces measurable antibody titers in elephants. An ELISA test was created to measure antibody responses to tetanus toxoid vaccinations in 22 Asian elephants ranging in age from 24 to 56 years (mean age 39 years) over a 7-month period. All animals had been previously vaccinated with tetanus toxoid vaccine, with the last booster administered 4 years before the start of the study. The great majority of elephants had titers prior to booster vaccination, and following revaccination all elephants demonstrated anamnestic increases in titers, indicating that this species does respond to tetanus vaccination. Surprisingly older animals mounted a significantly higher response to revaccination than did younger animals. Copyright 2009 Elsevier B.V. All rights reserved.
Pagliusi, Sonia; Ting, Ching-Chia; Lobos, Fernando
The Developing Countries Vaccine Manufacturers' Network (DCVMN) gathered leaders in immunization programs, vaccine manufacturing, representatives of the Argentinean Health Authorities and Pan American Health Organization, among other global health stakeholders, for its 17th Annual General Meeting in Buenos Aires, to reflect on how vaccines are shaping global health. Polio eradication and elimination of measles and rubella from the Americas is a result of successful collaboration, made possible by timely supply of affordable vaccines. After decades of intense competition for high-value markets, collaboration with developing countries has become critical, and involvement of multiple manufacturers as well as public- and private-sector investments are essential, for developing new vaccines against emerging infectious diseases. The recent Zika virus outbreak and the accelerated Ebola vaccine development exemplify the need for international partnerships to combat infectious diseases. A new player, Coalition for Epidemic Preparedness Innovations (CEPI) has made its entrance in the global health community, aiming to stimulate research preparedness against emerging infections. Face-to-face panel discussions facilitated the dialogue around challenges, such as risks of viability to vaccine development and regulatory convergence, to improve access to sustainable vaccine supply. It was discussed that joint efforts to optimizing regulatory pathways in developing countries, reducing registration time by up to 50%, are required. Outbreaks of emerging infections and the global Polio eradication and containment challenges are reminders of the importance of vaccines' access, and of the importance of new public-private partnerships. Copyright © 2017.
Dennehy, Penelope H
Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and has a major global impact on childhood morbidity and mortality. Vaccination is the only control measure likely to have a significant impact on the incidence of severe dehydrating rotavirus disease. Rotavirus disease prevention efforts suffered a great setback in 1999 with the withdrawal of the RRV-TV vaccine less than a year after its introduction. Several new rotavirus vaccine candidates have now been developed and are undergoing clinical trials. New safe and effective rotavirus vaccines offer the best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and developing countries.
Midthun, K; Kapikian, A Z
Rotavirus vaccine development has focused on the delivery of live attenuated rotavirus strains by the oral route. The initial "Jennerian" approach involving bovine (RIT4237, WC3) or rhesus (RRV) rotavirus vaccine candidates showed that these vaccines were safe, well tolerated, and immunogenic but induced highly variable rates of protection against rotavirus diarrhea. The goal of a rotavirus vaccine is to prevent severe illness that can lead to dehydration in infants and young children in both developed and developing countries. These studies led to the concept that a multivalent vaccine that represented each of the four epidemiologically important VP7 serotypes might be necessary to induce protection in young infants, the target population for vaccination. Human-animal rotavirus reassortants whose gene encoding VP7 was derived from their human rotavirus parent but whose remaining genes were derived from the animal rotavirus parent were developed as vaccine candidates. The greatest experience with a multivalent vaccine to date has been gained with the quadrivalent preparation containing RRV (VP7 serotype 3) and human-RRV reassortants of VP7 serotype 1, 2, and 4 specificity. Preliminary efficacy trial results in the United States have been promising, whereas a study in Peru has shown only limited protection. Human-bovine reassortant vaccines, including a candidate that contains the VP4 gene of a human rotavirus (VP4 serotype 1A), are also being studied.
Pagliusi, Sonia; Jain, Rishabh; Suri, Rajinder Kumar
The Developing Countries Vaccine Manufacturers' Network (DCVMN) held its fifteenth annual meeting from October 27-29, 2014, New Delhi, India. The DCVMN, together with the co-organizing institution Panacea Biotec, welcomed over 240 delegates representing high-profile governmental and nongovernmental global health organizations from 36 countries. Over the three-day meeting, attendees exchanged information about their efforts to achieve their shared goal of preventing death and disability from known and emerging infectious diseases. Special praise was extended to all stakeholders involved in the success of polio eradication in South East Asia and highlighted challenges in vaccine supply for measles-rubella immunization over the coming decades. Innovative vaccines and vaccine delivery technologies indicated creative solutions for achieving global immunization goals. Discussions were focused on three major themes including regulatory challenges for developing countries that may be overcome with better communication; global collaborations and partnerships for leveraging investments and enable uninterrupted supply of affordable and suitable vaccines; and leading innovation in vaccines difficult to develop, such as dengue, Chikungunya, typhoid-conjugated and EV71, and needle-free technologies that may speed up vaccine delivery. Moving further into the Decade of Vaccines, participants renewed their commitment to shared responsibility toward a world free of vaccine-preventable diseases. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Greenwood, Brian; Salisbury, David; Hill, Adrian V. S.
Vaccines have made a major contribution to global health in recent decades but they could do much more. In November 2011, a Royal Society discussion meeting, ‘New vaccines for global health’, was held in London to discuss the past contribution of vaccines to global health and to consider what more could be expected in the future. Papers presented at the meeting reviewed recent successes in the deployment of vaccines against major infections of childhood and the challenges faced in developing vaccines against some of the world's remaining major infectious diseases such as human immunodeficiency virus (HIV), malaria and tuberculosis. The important contribution that development of more effective veterinary vaccines could make to global health was also addressed. Some of the social and financial challenges to the development and deployment of new vaccines were reviewed. The latter issues were also discussed at a subsequent satellite meeting, ‘Accelerating vaccine development’, held at the Kavli Royal Society International Centre. Delegates at this meeting considered challenges to the more rapid development and deployment of both human and veterinary vaccines and how these might be addressed. Papers based on presentations at the discussion meeting and a summary of the main conclusions of the satellite meeting are included in this issue of Philosophical Transactions of the Royal Society B. PMID:21893534
Eric P. Zorrilla; Shinichi Iwasaki; Jason A. Moss; Jason Chang; Jonathan Otsuji; Koki Inoue; Michael M. Meijler; Kim D. Janda
.... Here we show that active vaccination of mature rats with ghrelin immunoconjugates decreases feed efficiency, relative adiposity, and body weight gain in relation to the immune response elicited...
Ford, John A; Mahgoub, Hamid; Shankar, Ananda Giri
The United Kingdom has had a long history with vaccine acceptability dating back to Edward Jenner's theory of small pox vaccination. More recently, the discredited, Wakefield study published in 1998 continues to cause MMR skepticism. In pregnant women pertussis vaccination has been considerably more successful than influenza vaccination. Influenza vaccine uptake in healthcare workers remains poor. The media, politicians, and health reforms have contributed to the mixed coverage for these vaccines. In this article we examine vaccine acceptability from a UK perspective, and consider the future impact this is likely to have on the introduction of rotavirus and shingles vaccine in the UK in 2013.
Adacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Boostrix® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)
... Professionals in Infection Control and Epidemiology (APIC). Increasing Flu Vaccination Rates among Healthcare Workers Position statements from professional organizations, mandatory influenza vaccination policies, and many helpful ...
Wang, Guomin; Zhu, Ruihao; Yang, Licong; Wang, Kaile; Zhang, Qian; Su, Xia; Yang, Bing; Zhang, Jue; Fang, Jing
Vaccines are of great importance in controlling the spread of infectious diseases in poultry farming. The safety and efficacy of vaccines are also essential. To explore the feasibility of a novel technology (non-thermal plasma) in inactivated vaccine preparation, an alternating current atmospheric pressure non-thermal plasma (NTP) jet with Ar/O2/N2 as the operating gas was used to inactivate a Newcastle disease virus (NDV, LaSota) strain and H9N2 avian influenza virus (AIV, A/Chicken/Hebei/WD/98) for vaccine preparation. The results showed that complete inactivation could be achieved with 2 min of NTP treatment for both NDV and AIV. Moreover, a proper NTP treatment time is needed for inactivation of a virus without destruction of the antigenic determinants. Compared to traditional formaldehyde-inactivated vaccine, the vaccine made from NDV treated by NTP for 2 min (NTP-2 min-NDV-vaccine) could induce a higher NDV-specific antibody titer in specific pathogen-free (SPF) chickens, and the results of a chicken challenge experiment showed that NTP-2 min-NDV-vaccine could protect SPF chickens from a lethal NDV challenge. Vaccines made from AIV treated by NTP for 2 min (NTP-2 min-AIV-vaccine) also showed a similar AIV-specific antibody titer compared with traditional AIV vaccines prepared using formaldehyde inactivation. Studies of the morphological changes of the virus, chemical analysis of NDV allantoic fluid and optical emission spectrum analysis of NTP suggested that reactive oxygen species and reactive nitrogen species produced by NTP played an important role in the virus inactivation process. All of these results demonstrated that it could be feasible to use non-thermal NTP as an alternative strategy to prepare inactivated vaccines for Newcastle disease and avian influenza. Copyright © 2015 Elsevier Ltd. All rights reserved.
Janewongwirot, Pakpoom; Puthanakit, Thanyawee; Anugulruengkitt, Suvaporn; Jantarabenjakul, Watsamon; Phasomsap, Chayapa; Chumket, Sompong; Yoksan, Sutee; Pancharoen, Chitsanu
Japanese Encephalitis chimeric virus vaccine (JE-CV) and SA14-14-2 vaccine are live-attenuated JE vaccines produced from the same virus strain. Data on interchangeability is limited. To evaluate the immunogenicity and safety of JE-CV booster after primary vaccination with SA14-14-2 vaccine. This study was an open-label clinical trial in Thai children who had received a primary SA14-14-2 vaccination at 12-24monthsbefore enrollment (ClinicalTrials.gov NCT02602652). JE-CV was administered. A 50% plaque reduction neutralization test (PRNT 50 ) against three virus strains; JE-CV, SA-14-14-2andwild-type JE virus was measured before and 28-days post vaccination. The laboratory was performed at PRNT 50 titers ⩾10 (1/dil) were considered seroprotective against JE. Geometric mean titer (GMT) of PRNT 50 was calculated. Adverse events were observed for 28days. From March 2014 to June 2015, 50 children (64% male) were enrolled. Mean age and duration after primary vaccination was 26.9 (SD 4.6) and 12.8 (SD 2.7) months, respectively. The proportion of participants who had PRNT 50 pre and post-booster vaccination were 92% and 96% against JE-CV virus, 56% and 98% against SA-14-14-2 strain and 70% and 98% against wild-type JE virus, respectively. Solicited injection site reactions including erythema, pain and swelling occurred in 18%, 10% and 4% of subjects, respectively. Four children (8%) had fever (⩾37.7Celsius). Eight children (16%) had adverse events, which were not related to the vaccine. AJE-CV booster dose is highly immunogenic and safe among children who previously received SA14-14-2 vaccine. Copyright © 2016 Elsevier Ltd. All rights reserved.
Daniel H. Libraty
Full Text Available Neonatal Bacille Calmette Guérin (BCG vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1 immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2–3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ producing spot-forming cells (SFC to tetanus toxoid 2–3 months later. The frequency of IFN-γ producing SFC to polioviruses 1–3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA/Ionomycin was higher in 2–3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2–3 months later.
Berlanda Scorza, Francesco; Tsvetnitsky, Vadim; Donnelly, John J
Influenza virus causes acute upper and lower respiratory infections and is the most likely, among known pathogens, to cause a large epidemic in humans. Influenza virus mutates rapidly, enabling it to evade natural and vaccine-induced immunity. Furthermore, influenza viruses can cross from animals to humans, generating novel, potentially pandemic strains. Currently available influenza vaccines induce a strain specific response and may be ineffective against new influenza viruses. The difficulty in predicting circulating strains has frequently resulted in mismatch between the annual vaccine and circulating viruses. Low-resource countries remain mostly unprotected against seasonal influenza and are particularly vulnerable to future pandemics, in part, because investments in vaccine manufacturing and stockpiling are concentrated in high-resource countries. Antibodies that target conserved sites in the hemagglutinin stalk have been isolated from humans and shown to confer protection in animal models, suggesting that broadly protective immunity may be possible. Several innovative influenza vaccine candidates are currently in preclinical or early clinical development. New technologies include adjuvants, synthetic peptides, virus-like particles (VLPs), DNA vectors, messenger RNA, viral vectors, and attenuated or inactivated influenza viruses. Other approaches target the conserved exposed epitope of the surface exposed membrane matrix protein M2e. Well-conserved influenza proteins, such as nucleoprotein and matrix protein, are mainly targeted for developing strong cross-protective T cell responses. With multiple vaccine candidates moving along the testing and development pipeline, the field is steadily moving toward a product that is more potent, durable, and broadly protective than previously licensed vaccines. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.
Huijskens, Elisabeth G. W.; Reimerink, Johan; Mulder, Paul G. H.; van Beek, Janko; Meijer, Adam; de Bruin, Erwin; Friesema, Ingrid; de Jong, Menno D.; Rimmelzwaan, Guus F.; Peeters, Marcel F.; Rossen, John W. A.; Koopmans, Marion
The influence of prior seasonal influenza vaccination on the antibody response produced by natural infection or vaccination is not well understood. We compared the profiles of antibody responses of 32 naturally infected subjects and 98 subjects vaccinated with a 2009 influenza A(H1N1) monovalent
Huijskens, Elisabeth G W; Reimerink, Johan; Mulder, Paul G H; van Beek, Janko; Meijer, Adam; de Bruin, Erwin; Friesema, Ingrid; de Jong, Menno D; Rimmelzwaan, Guus F; Peeters, Marcel F; Rossen, John W A; Koopmans, Marion
BACKGROUND: The influence of prior seasonal influenza vaccination on the antibody response produced by natural infection or vaccination is not well understood. METHODS: We compared the profiles of antibody responses of 32 naturally infected subjects and 98 subjects vaccinated with a 2009 influenza
Novel vaccine strategies include the so-called subunit vaccines, which encompass only the part of the pathogen to which immune recognition results in protection. The high purity of these vaccines make adverse events less likely, but it also makes the vaccines less immunogenic and therefore potentially less effective. Vaccine adjuvants that increase and modulate the immunogenicity of the vaccine are therefore added to solve this problem. Besides aluminum salts, which have been used in vaccines for 90 years, a number of novel vaccine adjuvants have been included in licensed vaccines over the last 30 years. Increasing insight into immunological mechanisms and how to manipulate them has replaced empirical with rational design of adjuvants, leading to vaccine adjuvants with increased and customized immunogenicity profiles without compromising vaccine safety.
Assessing vaccine efficacy for the prevention of acute otitis media by pneumococcal vaccination in children: a methodological overview of statistical practice in randomized controlled clinical trials.
Jahn-Eimermacher, Antje; du Prel, Jean-Baptist; Schmitt, Heinz-Josef
Acute otitis media (AOM) is the most common bacterial infectious disease among children. Vaccination is proposed to prevent otitis and several clinical trials were performed to assess the efficacy of pneumococcal vaccines. The way vaccine efficacy is analysed varies among trials. However, the clinical meaning of an estimate of vaccine effect and its statistical test depends on the applied statistical method. We aim to bring the meaning and validity of statistical trial results to the attention of researchers. We consider all methodological approaches for analysing vaccine efficacy applied in pneumococcal vaccination trials included in a recent Cochrane Review. We demonstrate how different methods address different scientific questions on the effect of vaccination, how they can complement each other and why some methods can produce misleading results.
Clarke, Steve; Giubilini, Alberto
ABSTRACT Vaccine refusal occurs for a variety of reasons. In this article we examine vaccine refusals that are made on conscientious grounds; that is, for religious, moral, or philosophical reasons. We focus on two questions: first, whether people should be entitled to conscientiously object to vaccination against contagious diseases (either for themselves or for their children); second, if so, to what constraints or requirements should conscientious objection (CO) to vaccination be subject. To address these questions, we consider an analogy between CO to vaccination and CO to military service. We argue that conscientious objectors to vaccination should make an appropriate contribution to society in lieu of being vaccinated. The contribution to be made will depend on the severity of the relevant disease(s), its morbidity, and also the likelihood that vaccine refusal will lead to harm. In particular, the contribution required will depend on whether the rate of CO in a given population threatens herd immunity to the disease in question: for severe or highly contagious diseases, if the population rate of CO becomes high enough to threaten herd immunity, the requirements for CO could become so onerous that CO, though in principle permissible, would be de facto impermissible. PMID:28008636
Lee, Bruce Y; McGlone, Sarah M
New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical, and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following ten components: 1. Conduct a target population analysis; 2. Map potential competitors and alternatives; 3. Construct a vaccine target product profile (TPP) and compare it to projected or actual TPPs of competing vaccines; 4. Quantify the incremental value of the new vaccine's characteristics; 5. Determine vaccine positioning in the marketplace; 6. Estimate the vaccine price-demand curve; 7. Calculate vaccine costs (including those of manufacturing, distribution, and research and development); 8. Account for various legal, regulatory, third party payer, and competitor factors; 9. Consider the overall product portfolio; 10. Set pricing objectives; 11. Select pricing and pricing structure. While the biomedical literature contains some studies that have addressed these components, there is still considerable room for more extensive evaluation of this important area.
Vaccine description. A highly purified vaccine containing 2~. Ilg of each of 23 capsular polysaccharides representing;;, 85% of the serotypes causing pneumonia and invasive pneumococcal disease in the community. Polysaccharide a.rltigens induce type-specific antibodies that enhance opsonisation, phagocytosis and ...
A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); G.F. Rimmelzwaan (Guus)
textabstractVaccination is the most cost-effective way to reduce the considerable disease burden of seasonal influenza. Although seasonal influenza vaccines are effective, their performance in the elderly and immunocompromised individuals would benefit from improvement. Major problems related to the
Ouattara, Amed; Laurens, Matthew B
Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
Numerous therapeutic strategies are used to treat leishmaniasis. The treatment of cutaneous leishmaniasis (CL) is solely depends on antimonate derivatives with safety issues and questionable efficacy and there is no fully effective modality to treat CL caused by Leishmania tropica and Leishmania braziliensis. There is no prophylactic vaccine available against any form of leishmaniasis. Immunotherapy for CL has a long history; immunotherapy trials of first and second generation vaccines showed promising results. The current article briefly covers the prophylactic vaccines and explains different immunotherapy strategies that have been used to treat leishmaniasis. This paper does not include experimental vaccines and only lays emphasis on human trials and those vaccines which reached human trials. Immunotherapy is currently used to successfully treat several disorders; Low cost, limited side effects and no possibility to develop resistance make immunotherapy a valuable choice especially for infectious disease with chemotherapy problems. Efforts are needed to explore the immunological surrogate marker(s) of cure and protection in leishmaniasis and overcome the difficulties in standardization of crude Leishmania vaccines. One of the reasons for anti-leishmaniasis vaccine failure is lack of an appropriate adjuvant. So far, not enough attention has been paid to develop vaccines for immunotherapy of leishmaniasis.
Ma, Barbara; Maraj, Bharat; Tran, Nam Phuong; Knoff, Jayne; Chen, Alexander; Alvarez, Ronald D; Hung, Chien-Fu; Wu, T.-C.
Introduction Identification of human papillomavirus (HPV) as the etiologic factor of cervical, anogenital, and a subset of head and neck cancers has stimulated the development of preventive and therapeutic HPV vaccines to control HPV-associated malignancies. Excitement has been generated by the commercialization of two preventive L1-based vaccines, which use HPV virus-like particles (VLPs) to generate capsid-specific neutralizing antibodies. However, factors such as high cost and requirement for cold chain have prevented widespread implementation where they are needed most. Areas covered Next generation preventive HPV vaccine candidates have focused on cost-effective stable alternatives and generating broader protection via targeting multivalent L1 VLPs, L2 capsid protein, and chimeric L1/L2 VLPs. Therapeutic HPV vaccine candidates have focused on enhancing T cell-mediated killing of HPV-transformed tumor cells, which constitutively express HPV-encoded proteins, E6 and E7. Several therapeutic HPV vaccines are in clinical trials. Expert opinion Although progress is being made, cost remains an issue inhibiting the use of preventive HPV vaccines in countries that carry the majority of the cervical cancer burden. In addition, progression of therapeutic HPV vaccines through clinical trials may require combination strategies employing different therapeutic modalities. As research in the development of HPV vaccines continues, we may generate effective strategies to control HPV-associated malignancies. PMID:23163511
Clarke, Steve; Giubilini, Alberto; Walker, Mary Jean
Vaccine refusal occurs for a variety of reasons. In this article we examine vaccine refusals that are made on conscientious grounds; that is, for religious, moral, or philosophical reasons. We focus on two questions: first, whether people should be entitled to conscientiously object to vaccination against contagious diseases (either for themselves or for their children); second, if so, to what constraints or requirements should conscientious objection (CO) to vaccination be subject. To address these questions, we consider an analogy between CO to vaccination and CO to military service. We argue that conscientious objectors to vaccination should make an appropriate contribution to society in lieu of being vaccinated. The contribution to be made will depend on the severity of the relevant disease(s), its morbidity, and also the likelihood that vaccine refusal will lead to harm. In particular, the contribution required will depend on whether the rate of CO in a given population threatens herd immunity to the disease in question: for severe or highly contagious diseases, if the population rate of CO becomes high enough to threaten herd immunity, the requirements for CO could become so onerous that CO, though in principle permissible, would be de facto impermissible. © 2016 The Authors Bioethics Published by John Wiley & Sons Ltd.
Schijns, V.E.J.C.; Lavelle, E.C.
Adjuvants are essential components of most clinically used vaccines. This is because the majority of nonliving vaccines are relatively poor inducers of adaptive immunity unless effective adjuvants are co-administered. Aluminum salts (alum) have been used as adjuvants with great success for almost a
Hotez, Peter J; Diemert, David; Bacon, Kristina M; Beaumier, Coreen; Bethony, Jeffrey M; Bottazzi, Maria Elena; Brooker, Simon; Couto, Artur Roberto; Freire, Marcos da Silva; Homma, Akira; Lee, Bruce Y; Loukas, Alex; Loblack, Marva; Morel, Carlos Medicis; Oliveira, Rodrigo Correa; Russell, Philip K
Hookworm infection is one of the world's most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries. A Human Hookworm Vaccine is currently being developed by the Sabin Vaccine Institute and is in phase 1 clinical testing. The candidate vaccine is comprised of two recombinant antigens known as Na-GST-1 and Na-APR-1, each of which is an important parasite enzyme required for hookworms to successfully utilize host blood as a source of energy. The recombinant proteins are formulated on Alhydrogel(®) and are being tested in combination with a synthetic Toll-like receptor 4 agonist. The aim of the vaccine is to induce anti-enzyme antibodies that will reduce both host blood loss and the number of hookworms attached to the gut. Transfer of the manufacturing technology to the Oswaldo Cruz Foundation (FIOCRUZ)/Bio-Manguinhos (a Brazilian public sector developing country vaccine manufacturer) is planned, with a clinical development plan that could lead to registration of the vaccine in Brazil. The vaccine would also need to be introduced in the poorest regions of Africa and Asia, where hookworm infection is highly endemic. Ultimately, the vaccine could become an essential tool for achieving hookworm control and elimination, a key target in the 2012 London Declaration on Neglected Tropical Diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.
meeting to consider the draft guideline. Financial sponsor. Development supported by an ... respiratory vaccinations consensus meeting was held in. Gauteng (see below). Participants were invited ..... Boorman D. Influenza vaccine and its relationship to absenteeism in the workplace. Occupational Health SA 1997; 3: 29-30.
... breastfeeding. The father of the baby received the HPV vaccine around the time that I got pregnant. Is there a risk to the baby? No. There is no evidence that vaccines given to men will affect the sperm. In general, exposures that fathers have are unlikely ...
Lehmann, B.; Eilers, R.; Donken, R.; Barug, D.; Swillens, J.; Vriend, C. de; Weerdenburg, S.; Pot, M.; Keulen, H. van; Paulussen, T.; Vermey, K.; Alberts, N.; Marra, E.; Melker, H.E. de; Mollema, L.
Both in 2013 and 2015 the mean intention of parents to vaccinate their child was high. Only 21% of parents reported making an informed decision about childhood vaccinations included in the NIP. Mass media attention on the use of allegedly inferior needles, which was later refuted, appeared to have a
Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine.
... representative in the case of a child) receiving vaccines covered under the National Vaccine Injury Compensation... influenza vaccine each year. But some children younger than 9 years of age need 2 doses to be protected. Ask... months should not get either influenza vaccine.) Children younger than 5 with asthma or one or more...
... representative in the case of a child) receiving vaccines covered under the National Vaccine Injury Compensation... HUMAN SERVICES Centers for Disease Control and Prevention Proposed Vaccine Information Materials for Rotavirus Vaccine AGENCY: Centers for Disease Control and Prevention (CDC), Department of Health and Human...
Despite great public interest and desperate need, progress toward a viable human immunodeficiency virus (HIV) vaccine remains incredibly slow. Since Merck began its HIV vaccine research in 1985, the pharmaceutical company has yet to produce a vaccine capable of passing Phase II testing. Merck Laboratories President Peter S. Kim recently delivered a speech at Yale University that detailed his company’s previous attempts to create an HIV vaccine and outlined a possible strategy for the future. By Kim’s own admission, Merck will not produce a viable vaccine in the near future. However, the speech served as an important endorsement for HIV vaccine development from a highly respected leader in the pharmaceutical industry, which, historically, has produced drugs aimed at management rather than prevention. PMID:21698049
Despite great public interest and desperate need, progress toward a viable human immunodeficiency virus (HIV) vaccine remains incredibly slow. Since Merck began its HIV vaccine research in 1985, the pharmaceutical company has yet to produce a vaccine capable of passing Phase II testing. Merck Laboratories President Peter S. Kim recently delivered a speech at Yale University that detailed his company's previous attempts to create an HIV vaccine and outlined a possible strategy for the future. By Kim's own admission, Merck will not produce a viable vaccine in the near future. However, the speech served as an important endorsement for HIV vaccine development from a highly respected leader in the pharmaceutical industry, which, historically, has produced drugs aimed at management rather than prevention.
Andersson, Anne Marie C.; Schwerdtfeger, Melanie; Holst, Peter J.
Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (......Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus...... of HIV. Such vaccines are immunologically perceived as viruses, as they infect cells and produce VLPs in situ, but they only resemble viruses, as the replication defective vectors and VLPs cannot propagate an infection. The inherent safety of such a platform, despite robust particle production...
Full Text Available The aim of the review was to emphasize the importance of producing new generation high standardized synthetic peptide Zika vaccines which induce both humoral and cellular immunity and eliminate side effects of traditional vaccines. The information was done about Zika virus that is an artropod-born virus, member of the genus Flavivirus in the family Flaviviridae. Zika virus has caused outbreaks in many countries the conditions in adults such as Guillain–Barre syndrome by the dramatically increasing number of cases. According to announcement by World Health Organization, 4 million people could be infected with Zika virus in Americas. The importance of the development of peptide vaccines against the virus Zika of the new generation, which are the most promising direction of the prevention and treatment of viral infection has emphasized.
Matsubara, Akihiro; Shimizu, Yuya; Karamatsu, Katsuo; Yasutomi, Yasuhiro
In the increasing crisis of pandemic of infectious diseases all over the world in recent years, it is the most necessary to develop readily available vaccines even in developing countries. Since many pathogens establish their initial infections through the mucosal surface in our bodies, the induction of mucosal immune responses by vaccines are thought to be important for the prevention of infectious diseases through mucosal site. Oral administration of vaccines has abilities to elicit mucosal immune responses at mucosal tissues with various advantages such as easy skill for administration, less stressful for vaccine recipients and safer than systemic injection. Here, we show our novel strategies for inducing mucosal immune responses by oral vaccine administration.
Mailand, Mia Topsøe; Frederiksen, Jette Lautrup
Vaccinations are often the most effective tool against some disease known to mankind. This study offers a literature review on the role of vaccines regarding the risk of developing multiple sclerosis (MS) and MS relapse. The method used in this study is a systematic literature review on the datab......Vaccinations are often the most effective tool against some disease known to mankind. This study offers a literature review on the role of vaccines regarding the risk of developing multiple sclerosis (MS) and MS relapse. The method used in this study is a systematic literature review...... on the database PubMed. The study found no change in risk of developing multiple sclerosis (MS) after vaccination against hepatitis B virus, human papillomavirus, seasonal influenza, measles-mumps-rubella, variola, tetanus, Bacillus Calmette-Guérin (BCG), polio, or diphtheria. No change in risk of relapse...
Williams, Walter W; Lu, Peng-Jun; O'Halloran, Alissa; Bridges, Carolyn B; Kim, David K; Pilishvili, Tamara; Hales, Craig M; Markowitz, Lauri E
Vaccinations are recommended throughout life to prevent vaccine-preventable diseases and their sequelae. Adult vaccination coverage, however, remains low for most routinely recommended vaccines and below Healthy People 2020 targets. In October 2014, the Advisory Committee on Immunization Practices (ACIP) approved the adult immunization schedule for 2015. With the exception of influenza vaccination, which is recommended for all adults each year, other adult vaccinations are recommended for specific populations based on a person's age, health conditions, behavioral risk factors (e.g., injection drug use), occupation, travel, and other indications. To assess vaccination coverage among adults aged ≥19 years for selected vaccines, CDC analyzed data from the 2013 National Health Interview Survey (NHIS). This report highlights results of that analysis for pneumococcal, tetanus toxoid-containing (tetanus and diphtheria vaccine [Td] or tetanus and diphtheria with acellular pertussis vaccine [Tdap]), hepatitis A, hepatitis B, herpes zoster (shingles), and human papillomavirus (HPV) vaccines by selected characteristics (age, race/ethnicity,† and vaccination indication). Influenza vaccination coverage estimates for the 2013-14 influenza season have been published separately. Compared with 2012, only modest increases occurred in Tdap vaccination among adults aged ≥19 years (a 2.9 percentage point increase to 17.2%), herpes zoster vaccination among adults aged ≥60 years (a 4.1 percentage point increase to 24.2%), and HPV vaccination among males aged 19-26 years (a 3.6 percentage point increase to 5.9%); coverage among adults in the United States for the other vaccines did not improve. Racial/ethnic disparities in coverage persisted for all six vaccines and widened for Tdap and herpes zoster vaccination. Increases in vaccination coverage are needed to reduce the occurrence of vaccine-preventable diseases among adults. Awareness of the need for vaccines for adults is low
Rijpkema, Sjoerd G; Adams, Trudy; Rigsby, Peter; Xing, Dorothy K; Corbel, Michael J
The toxicity and immunogenicity of the anthrax and pertussis vaccine combinations used in the 1991 Gulf War was assessed in NIH, A/J and Balb/c mice. Inoculation of pertussis vaccines, vaccine combinations, or aluminium salt caused illness, splenomegaly and significant weight loss. Although some animals recovered eventually, a lethal form of ascites developed in some NIH mice and body weights of A/J and Balb/c mice remained below normal levels. Inoculation of anthrax vaccine produced little effect. Exposure to diluted vaccine combinations produced less serious side effects of shorter duration. Single vaccinations induced specific IgG1 antibodies whereas a mixture of IgG1 and IgG2a was produced after multiple injections. Antigen stimulation of spleen cells from mice exposed to pertussis vaccines induced high levels of NO and IL-6, whereas stimulated spleen cells from mice exposed to anthrax vaccine produced only low levels of IL-6. In mice, pertussis vaccines act as an adjuvant for anthrax vaccine, but these vaccines are also the major cause of toxicity of the vaccine combination. The relatively high vaccine dose used, together with the low sensitivity of mice to anthrax toxin, emphasises that caution should be exercised in applying these results to human recipients of these vaccines.
Palatnik-de-Sousa, Clarisa B
Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL) is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global warming, coinfection with immunosuppressive diseases, and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL) in the Americas, the Middle East, Central Asia, China, and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases, and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost-effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine VL. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans and dogs against VL.
Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C
Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines. PMID:25424797
Clarisa B. Palatnik-De-Sousa
Full Text Available Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global-warming, co-infection with immunosuppressive diseases and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL in the Americas, the Middle East, Central Asia, China and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost-effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine visceral leishmaniasis. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans
Palatnik-de-Sousa, Clarisa B.
Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL) is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global warming, coinfection with immunosuppressive diseases, and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL) in the Americas, the Middle East, Central Asia, China, and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases, and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost–effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine VL. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans and dogs against VL. PMID:22566950
Full Text Available Human communication is of a persuasive character, since the perspective to determine the difference between fact and opinion differ according to sociological and cultural backgrounds. Media sets the ground for building stereotypes by imposing the ideas to the recipients. It makes media a tool for persuasive communication thus producing the effects of what a vaccine injection might do to a human body. As language is one of the most used tools in media, this stealthy persuasion operates on a subtle "antigens" infiltrated in the context of the media text. "Mind vaccinating" recipients by media eventually can lead to stereotyped perceptions and produce prejudice. In this metaphor vaccine antigens offer a persuasive perspective on reality immune to other perspectives but that one that is imposed by media. If a recipient in the communication process understands the threat then the persuasive effects are lessened as is explained in inoculation theory. If the threat is candy wrapped in media content, as is done so by the demand of market and recipients themselves (and imposed by politics and corporation interest, then the threat is no longer understood as a threat by the recipient. The immune system is vaccinated and protected from the disease of free thinking. The disease represents a reality that is not shape shifted by someone else. Shape shifted reality is distributed through the vaccines. Media being the vaccine makes it a powerful tool in the persuasive strategy for shape shifting the reality based on framed and reframed facts and opinions of the majority in democratized media. Media is consciously or unconsciously shape shifting the reality, which makes it a tool of persuasion.
Sefidi, Fatemeh Jahanbakhsh; Kaghazian, Homan; Moradli, Gholam Ali; Hassanzadeh, Seyed Mehdi
Background: Thermal stability (TS) is a part of the BCG vaccine characterization by which the consistency of process in BCG vaccine production could be confirmed. To enhance the TS of the vaccine, some prevalent stabilizers in different concentrations were added to the final formulation of BCG bulk prior to Freeze-drying process. We found a formulation more effective than the current stabilizer for retaining the higher viability of lyophilized BCG vaccine produced by Pasteur Institute of Iran. Methods: In the design of experiments using Taguchi method, lactose, trehalose, glucose, dextran, and monosodium glutamate were added to the final formulation of BCG bulk prior to freeze-drying process. Viability of the samples was determined by counting the colony forming unit. Results: Maximum signal-to-noise ratio equal to maximum TS and viability was obtained by adding lactose, dextran, and glutamate in defined concentrations. Conclusion: Adding the stabilizers had a significant impact on TS of BCG vaccine to meet the quality requirements. PMID:28605892
Bethony, Jeffrey M.; Cole, Rhea N.; Guo, Xiaoti; Kamhawi, Shaden; Lightowlers, Marshall W.; Loukas, Alex; Petri, William; Reed, Steven; Valenzuela, Jesus G.; Hotez, Peter J.
Summary The neglected tropical diseases (NTDs) represent a group of parasitic and related infectious diseases such as amebiasis, Chagas disease, cysticercosis, echinococcosis, hookworm, leishmaniasis, and schistosomiasis. Together, these conditions are considered the most common infections in low- and middle-income countries, where they produce a level of global disability and human suffering equivalent to better known conditions such as human immunodeficiency virus/acquired immunodeficiency syndrome and malaria. Despite their global public health importance, progress on developing vaccines for NTD pathogens has lagged because of some key technical hurdles and the fact that these infections occur almost exclusively in the world’s poorest people living below the World Bank poverty line. In the absence of financial incentives for new products, the multinational pharmaceutical companies have not embarked on substantive research and development programs for the neglected tropical disease vaccines. Here, we review the current status of scientific and technical progress in the development of new neglected tropical disease vaccines, highlighting the successes that have been achieved (cysticercosis and echinococcosis) and identifying the challenges and opportunities for development of new vaccines for NTDs. Also highlighted are the contributions being made by non-profit product development partnerships that are working to overcome some of the economic challenges in vaccine manufacture, clinical testing, and global access. PMID:21198676
Full Text Available Although rabies incidence has fallen sharply over the past decades in Europe, the disease is still present in Eastern Europe. Oral rabies immunization of wild animal rabies has been shown to be the most effective method for the control and elimination of rabies. All rabies vaccines used in Europe are modified live virus vaccines based on the Street Alabama Dufferin (SAD strain isolated from a naturally-infected dog in 1935. Because of the potential safety risk of a live virus which could revert to virulence, the genetic composition of three commercial attenuated live rabies vaccines was investigated in two independent laboratories using next genome sequencing. This study is the first one reporting on the diversity of variants in oral rabies vaccines as well as the presence of a mix of at least two different variants in all tested batches. The results demonstrate the need for vaccine producers to use new robust methodologies in the context of their routine vaccine quality controls prior to market release.
Cliquet, Florence; Picard-Meyer, Evelyne; Mojzis, Miroslav; Dirbakova, Zuzana; Muizniece, Zita; Jaceviciene, Ingrida; Mutinelli, Franco; Matulova, Marta; Frolichova, Jitka; Rychlik, Ivan; Celer, Vladimir
Although rabies incidence has fallen sharply over the past decades in Europe, the disease is still present in Eastern Europe. Oral rabies immunization of wild animal rabies has been shown to be the most effective method for the control and elimination of rabies. All rabies vaccines used in Europe are modified live virus vaccines based on the Street Alabama Dufferin (SAD) strain isolated from a naturally-infected dog in 1935. Because of the potential safety risk of a live virus which could revert to virulence, the genetic composition of three commercial attenuated live rabies vaccines was investigated in two independent laboratories using next genome sequencing. This study is the first one reporting on the diversity of variants in oral rabies vaccines as well as the presence of a mix of at least two different variants in all tested batches. The results demonstrate the need for vaccine producers to use new robust methodologies in the context of their routine vaccine quality controls prior to market release.
Yaguchi, K; Ohgitani, T; Noro, T; Kaneshige, T; Shimizu, Y
One hundred and twenty 30-day-old specific-pathogen-free chickens were inoculated with the liposomal inactivated avian pathogenic Escherichia coli (APEC) vaccine by eye drop or coarse spraying. All of the chickens produced anti-lipopolysaccharide antibodies of the IgG subclass in their sera as well as IgA antibodies in their oral mucus. The results demonstrated a rise in antibodies in the serum of chickens administered the APEC vaccine through nonparenteral mucosal routes. Bacterial counts in the blood decreased, and clinical signs were moderated in the vaccinated chickens after challenge with a strain of APEC. No harmful effects from the vaccination were observed. The liposomal inactivated APEC vaccine described in this paper would contribute to a practical method of control for avian colibacillosis.
Lamphear, Barry J; Jilka, Joseph M; Kesl, Lyle; Welter, Mark; Howard, John A; Streatfield, Stephen J
Recombinant plant expression systems offer a means to produce large quantities of selected antigens for subunit vaccines. Cereals are particularly well-suited expression vehicles since the expressed proteins can be stored at relatively high concentrations for extended periods of time without degradation and dry seed can be formulated into oral vaccines suitable for commercial applications. A subunit vaccine candidate directed against porcine transmissible gastroenteritis virus and expressed in corn seed has been developed for oral delivery to swine. Here, we show that this vaccine, when administered to previously sensitized gilts, can boost neutralizing antibody levels in the animals' serum, colostrum and milk. Thus, this vaccine candidate is effective at boosting lactogenic immunity and is appropriate to pursue through large-scale field trials preceding commercialization.
Full Text Available Abstract Background Although routine vaccination is a major tool in the primary prevention of some infectious diseases, there is some reluctance in a proportion of the population. Negative parental perceptions of vaccination are an important barrier to paediatric vaccination. The aim of this study was to investigate parental knowledge of paediatric vaccines and vaccination in Catalonia. Methods A retrospective, cross-sectional study was carried out in children aged Results An association was observed between greater vaccination coverage of the 4:4:4:3:1 schedule (defined as: 4 DTPa/w doses, 4 Hib doses, 4 OPV doses, 3 MenC doses and 1 MMR dose and maternal age >30 years (OR: 2.30; 95% CI: 1.20–4.43 and with a knowledge of vaccination score greater than the mean (OR: 0.45; 95% CI: 0.28–0.72. The score increased with maternal educational level and in parents of vaccinated children. A total of 20.47% of parents stated that vaccines could have undesirable consequences for their children. Of these, 23.26% had no specific information and 17.83% stated that vaccines can cause adverse reactions and the same percentage stated that vaccines cause allergies and asthma. Conclusion Higher vaccination coverage is associated with older maternal age and greater knowledge of vaccination. Vaccination coverage could be raised by improving information on vaccines and vaccination.
He, Yongqun; Xiang, Zuoshuang
Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis, one of the commonest zoonotic diseases found worldwide in humans and a variety of animal species. While several animal vaccines are available, there is no effective and safe vaccine for prevention of brucellosis in humans. VIOLIN (http://www.violinet.org) is a web-based vaccine database and analysis system that curates, stores, and analyzes published data of commercialized vaccines, and vaccines in clinical trials or in research. VIOLIN contains information for 454 vaccines or vaccine candidates for 73 pathogens. VIOLIN also contains many bioinformatics tools for vaccine data analysis, data integration, and vaccine target prediction. To demonstrate the applicability of VIOLIN for vaccine research, VIOLIN was used for bioinformatics analysis of existing Brucella vaccines and prediction of new Brucella vaccine targets. VIOLIN contains many literature mining programs (e.g., Vaxmesh) that provide in-depth analysis of Brucella vaccine literature. As a result of manual literature curation, VIOLIN contains information for 38 Brucella vaccines or vaccine candidates, 14 protective Brucella antigens, and 68 host response studies to Brucella vaccines from 97 peer-reviewed articles. These Brucella vaccines are classified in the Vaccine Ontology (VO) system and used for different ontological applications. The web-based VIOLIN vaccine target prediction program Vaxign was used to predict new Brucella vaccine targets. Vaxign identified 14 outer membrane proteins that are conserved in six virulent strains from B. abortus, B. melitensis, and B. suis that are pathogenic in humans. Of the 14 membrane proteins, two proteins (Omp2b and Omp31-1) are not present in B. ovis, a Brucella species that is not pathogenic in humans. Brucella vaccine data stored in VIOLIN were compared and analyzed using the VIOLIN query system. Bioinformatics curation and ontological representation of Brucella vaccines
Hernández-Ávila, Mauricio; Lazcano-Ponce, Eduardo; Hernández-Ávila, Juan Eugenio; Alpuche-Aranda, Celia M; Rodríguez-López, Mario Henry; García-García, Lourdes; Madrid-Marina, Vicente; López Gatell-Ramírez, Hugo; Lanz-Mendoza, Humberto; Martínez-Barnetche, Jesús; Díaz-Ortega, José Luis; Ángeles-Llerenas, Angélica; Barrientos-Gutiérrez, Tonatiuh; Bautista-Arredondo, Sergio; Santos-Preciado, José Ignacio
Dengue is a major global public health problem affecting Latin America and Mexico Prevention and control measures, focusing on epidemiological surveillance and vector control, have been partially effective and costly, thus, the development of a vaccine against dengue has created great expectations among health authorities and scientific communities worldwide. The CYD-TDV dengue vaccine produced by Sanofi-Pasteur is the only dengue vaccine evaluated in phase 3 controlled clinical trials. Notwithstanding the significant contribution to the development of a vaccine against dengue, the three phase 3 clinical studies of CYD-TDV and the meta-analysis of the long-term follow up of those studies, have provided evidence that this vaccine exhibited partial vaccine efficacy to protect against virologically confirmed dengue and lead to four considerations: a) adequate vaccine efficacy against dengue virus (DENV) infections 3 and 4, less vaccine efficacy against DENV 1 and no protection against infection by DENV 2; b) decreased vaccine efficacy in dengue seronegative individuals at the beginning of the vaccination; c) 83% and 90% protection against hospitalizations and severe forms of dengue, respectively, at 25 months follow-up; and d) increased hospitalization for dengue in the vaccinated group, in children under nine years of age at the time of vaccination, detected since the third year of follow-up. The benefit of the CYD-TDV vaccine can be summarized in the protection against infection by DENV 3 and 4, as well as protection for hospitalizations and severe cases in people over nine years, who have had previous dengue infection, working mainly as a booster. In this review we identified elements on efficacy and safety of this vaccine that must be taken into account in the licensing process and potential inclusion in the national vaccination program of Mexico. The available scientific evidence on the CYD-TDV vaccine shows merits, but also leads to relevant questions that
Matteucci, Donatella; Poli, Alessandro; Mazzetti, Paola; Sozzi, Sabrina; Bonci, Francesca; Isola, Patrizia; Zaccaro, Lucia; Giannecchini, Simone; Calandrella, Michela; Pistello, Mauro; Specter, Steven; Bendinelli, Mauro
Attempts at vaccine development for feline immunodeficiency virus (FIV) have been extensive, both because this is a significant health problem for cats and because FIV may be a useful vaccine model for human immunodeficiency virus. To date, only modest success, producing only short-term protection, has been achieved for vaccine trials in controlled laboratory settings. It is unclear how relevant such experiments are to prevention of natural infection. The current study used a vaccine that emp...
Sano, Kaori; Ainai, Akira; Suzuki, Tadaki; Hasegawa, Hideki
Influenza virus causes an acute respiratory infection in humans. Frequent point mutations in the influenza genome and occasional exchange of genetic segments between virus strains help the virus evade the pre-existing immunity, resulting in epidemics and pandemics. Although vaccination is the most effective intervention, mismatches between circulating viruses and vaccine strains reduce vaccine efficacy. Furthermore, current injectable vaccines induce IgG antibodies in serum (which limit progression of influenza symptoms) but not secretory IgA antibodies in the respiratory mucosa (which prevent virus infection efficiently). Therefore, numerous studies have attempted to improve influenza vaccines. The discovery of broadly neutralizing antibodies has progressed research into antigen design. Studies designed to improve vaccine efficacy by changing the vaccine administration route have also been conducted. A thorough understanding of the mechanisms underlying the action of various vaccines is essential if we are to develop a universal influenza vaccine. Therefore, evaluating the quality and quantity of antibodies induced by vaccines, which determine vaccine efficacy, is critical. However, at present vaccine evaluation relies on hemagglutination inhibition tests, which only measure the quantity of antibody produced. Antibody repertoires comprise a set of antibodies with specific genetic or molecular features that correspond to their functions. Genetically and functionally similar antibodies may be produced by multiple individuals exposed to an identical stimulus. Therefore, it may be possible to evaluate and compare multiple vaccine strategies in terms of the quality and quantity of an antibody response induced by a vaccine by examining antibody repertoires. Recent studies have used single cell expression and high-throughput immunoglobulin sequencing to provide a detailed picture of antibody responses. These novel methods may be critical for detailed characterization of
Amanda L. Wilkins
Full Text Available Influenza is a major cause of respiratory disease leading to hospitalization in young children. However, seasonal trivalent influenza vaccines (TIVs have been shown to be ineffective and poorly immunogenic in this population. The development of live-attenuated influenza vaccines and adjuvanted vaccines are important advances in the prevention of influenza in young children. The oil-in-water emulsions MF59 and adjuvant systems 03 (AS03 have been used as adjuvants in both seasonal adjuvanted trivalent influenza vaccines (ATIVs and pandemic monovalent influenza vaccines. Compared with non-adjuvanted vaccine responses, these vaccines induce a more robust and persistent antibody response for both homologous and heterologous influenza strains in infants and young children. Evidence of a significant improvement in vaccine efficacy with these adjuvanted vaccines resulted in the use of the monovalent (A/H1N1 AS03-adjuvanted vaccine in children in the 2009 influenza pandemic and the licensure of the seasonal MF59 ATIV for children aged 6 months to 2 years in Canada. The mechanism of action of MF59 and AS03 remains unclear. Adjuvants such as MF59 induce proinflammatory cytokines and chemokines, including CXCL10, but independently of type-1 interferon. This proinflammatory response is associated with improved recruitment, activation and maturation of antigen presenting cells at the injection site. In young children MF59 ATIV produced more homogenous and robust transcriptional responses, more similar to adult-like patterns, than did TIV. Early gene signatures characteristic of the innate immune response, which correlated with antibody titers were also identified. Differences were detected when comparing child and adult responses including opposite trends in gene set enrichment at day 3 postvaccination and, unlike adult data, a lack of correlation between magnitude of plasmablast response at day 7 and antibody titers at day 28 in children. These insights
Wilkins, Amanda L.; Kazmin, Dmitri; Napolitani, Giorgio; Clutterbuck, Elizabeth A.; Pulendran, Bali; Siegrist, Claire-Anne; Pollard, Andrew J.
Influenza is a major cause of respiratory disease leading to hospitalization in young children. However, seasonal trivalent influenza vaccines (TIVs) have been shown to be ineffective and poorly immunogenic in this population. The development of live-attenuated influenza vaccines and adjuvanted vaccines are important advances in the prevention of influenza in young children. The oil-in-water emulsions MF59 and adjuvant systems 03 (AS03) have been used as adjuvants in both seasonal adjuvanted trivalent influenza vaccines (ATIVs) and pandemic monovalent influenza vaccines. Compared with non-adjuvanted vaccine responses, these vaccines induce a more robust and persistent antibody response for both homologous and heterologous influenza strains in infants and young children. Evidence of a significant improvement in vaccine efficacy with these adjuvanted vaccines resulted in the use of the monovalent (A/H1N1) AS03-adjuvanted vaccine in children in the 2009 influenza pandemic and the licensure of the seasonal MF59 ATIV for children aged 6 months to 2 years in Canada. The mechanism of action of MF59 and AS03 remains unclear. Adjuvants such as MF59 induce proinflammatory cytokines and chemokines, including CXCL10, but independently of type-1 interferon. This proinflammatory response is associated with improved recruitment, activation and maturation of antigen presenting cells at the injection site. In young children MF59 ATIV produced more homogenous and robust transcriptional responses, more similar to adult-like patterns, than did TIV. Early gene signatures characteristic of the innate immune response, which correlated with antibody titers were also identified. Differences were detected when comparing child and adult responses including opposite trends in gene set enrichment at day 3 postvaccination and, unlike adult data, a lack of correlation between magnitude of plasmablast response at day 7 and antibody titers at day 28 in children. These insights show the utility
While most agree that vaccination is one of the most important public health practices, vaccines continue to be underused and undervalued, and vaccine-preventable diseases remain a threat to world health. Perhaps one reason this gap remains is that decision-making generally is made on a vaccine-by-vaccine basis. There has been less attention to the value of vaccination in general. To more clearly identify this value, this paper reviews the cost-effectiveness literature and calculates the annual benefits of vaccination on a global scale.
Gnanasekaran, Gowrishankar; Biedenbender, Rex; Davidson, Harley Edward; Gravenstein, Stefan
Vaccine response declines with age, but currently recommended vaccines are safe and effective in reducing, if not preventing, disease altogether. Over the last decade, advancements in vaccine immunogenicity, either by increasing dose or conjugating vaccines to protein, have resulted in more immunogenic vaccines that also seem more effective in reducing clinical disease both for influenza and pneumococcus. Meanwhile, there is a resurgence in incident pertussis, exceeding prevalence from five decades ago, adding older adults to a recommended target vaccination group. This article discusses currently available vaccines, in the context of current epidemiology and recommendations, for older adults. Copyright © 2016 Elsevier Inc. All rights reserved.
Lu, Shan; Wang, Shixia
Biodefense vaccines are developed against a diverse group of pathogens. Vaccines were developed for some of these pathogens a long time ago but they are facing new challenges to move beyond the old manufacturing technologies. New vaccines to be developed against other pathogens have to determine whether to follow traditional vaccination strategies or to seek new approaches. Advances in basic immunology and recombinant DNA technology have fundamentally transformed the process of formulating a vaccine concept, optimizing protective antigens, and selecting the most effective vaccine delivery approach for candidate biodefense vaccines. PMID:19837293
Full Text Available DNA, the essential part of the life is making way in to new vaccine technology. Plasmid vectors from the bacteria have revolutionized the world of vaccine design by its new technology DNA vaccines. Small portion of the nucleotides from the pathogen held under the control of promoter in a plasmid vector can be used as a vaccine. DNA vaccines alleviate the odds of the other vaccines by having good hold on both the faces of the immunity. The key to the success of DNA vaccine lies in the route of administration of the vaccine which can be done in many ways. Prime boost strategy is an approach used to boost the action of DNA vaccine. To date there are only four DNA vaccine available in the market. [Vet World 2013; 6(4.000: 228-232
group that invented an inactivated cell culture JEV vaccine produced in vero cells that became licensed in the US based on demonstration of...proposed hepatitis E vaccine efficacy trial in Nepal, and organized team at WRAIR to invent replacement JEV vaccine produced in vero cells Rapin Snitbahn...ScienceDirect Vaccine jou rn al hom ep age: www.elsev ier .com/ locat e/vacc ine eview model international partnership for community-based research on
Full Text Available Evolution of Bordetella pertussis is driven by natural and vaccine pressures. Isolates circulating in regions with high vaccination coverage present multiple allelic and antigenic variations as compared to isolates collected before introduction of vaccination. Furthermore, during the last epidemics reported in regions using pertussis acellular vaccines, isolates deficient for vaccine antigens, such as pertactin (PRN, were reported to reach high proportions of circulating isolates. More sporadic filamentous hemagglutinin (FHA or pertussis toxin (PT deficient isolates were also collected. The whole genome of some recent French isolates, deficient or non-deficient in vaccine antigens, were analyzed. Transcription profiles of the expression of the main virulence factors were also compared. The invasive phenotype in an in vitro human tracheal epithelial (HTE cell model of infection was evaluated. Our genomic analysis focused on SNPs related to virulence genes known to be more likely to present allelic polymorphism. Transcriptomic data indicated that isolates circulating since the introduction of pertussis vaccines present lower transcription levels of the main virulence genes than the isolates of the pre-vaccine era. Furthermore, isolates not producing FHA present significantly higher expression levels of the entire set of genes tested. Finally, we observed that recent isolates are more invasive in HTE cells when compared to the reference strain, but no multiplication occurs within cells.
Vrdoljak, Anto; McGrath, Marie G; Carey, John B; Draper, Simon J; Hill, Adrian V S; O'Mahony, Conor; Crean, Abina M; Moore, Anne C
Vaccines are sensitive biologics that require continuous refrigerated storage to maintain their viability. The vast majority of vaccines are also administered using needles and syringes. The need for cold chain storage and the significant logistics surrounding needle-and-syringe vaccination is constraining the success of immunization programs. Recombinant live viral vectors are a promising platform for the development of vaccines against a number of infectious diseases, however these viruses must retain infectivity to be effective. Microneedles offer an effective and painless method for delivery of vaccines directly into skin that in the future could provide solutions to current vaccination issues. Here we investigated methods of coating live recombinant adenovirus and modified vaccinia virus Ankara (MVA) vectors onto solid microneedle arrays. An effective spray-coating method, using conventional pharmaceutical processes, was developed, in tandem with suitable sugar-based formulations, which produces arrays with a unique coating of viable virus in a dry form around the shaft of each microneedle on the array. Administration of live virus-coated microneedle arrays successfully resulted in virus delivery, transcutaneous infection and induced an antibody or CD8(+) T cell response in mice that was comparable to that obtained by needle-and-syringe intradermal immunization. To our knowledge, this is the first report of successful vaccination with recombinant live viral vectored vaccines coated on microneedle delivery devices. Copyright © 2011 Elsevier B.V. All rights reserved.
Full Text Available Background: Worldwide tobacco is the leading cause of preventable death. Anew treatment in smoking cessation and relapse prevention is nicotine vaccination which is based on active immunization against the nicotine molecule. This article aimed to review the mechanism of action, current status of research and future aspects for the development of vaccines against nicotine. Materials & Method: The literature search of publications indexed was carried out in PubMed, Medline, Google scholar databases. Total 25 animal trials, human trials under various phases of clinical trials, unpublished document and cross-sectional survey were reviewed. Results: This immunization will act on immune system to produce nicotine-specific antibodies that sequester nicotine in the blood stream, after inhaling tobacco products. Nicotine vaccines are irreversible, provide protection over years and need booster injections. Efficiency of the vaccines is directly related to the antibody levels which help to optimize the vaccine effect. Nicotine vaccines are today in an advanced stage of clinical evaluation trials. Conclusions: Though, nicotine vaccine has considerable therapeutic potential, they do not target the non pharmacological factors that maintain tobacco dependence. So combination of nicotine vaccine with behavioral interventions would be effective mode to motivate abstinence from tobacco use.
Ulmer, Jeffrey B; Mansoura, Monique K; Geall, Andrew J
Self-amplifying mRNA vaccines are being developed as a platform technology with potential to be used for a broad range of targets. The synthetic production methods for their manufacture, combined with the modern tools of bioinformatics and synthetic biology, enable these vaccines to be produced rapidly from an electronic gene sequence. Preclinical proof of concept has so far been achieved for influenza, respiratory syncytial virus, rabies, Ebola, cytomegalovirus, human immunodeficiency virus and malaria. This editorial highlights the key milestones in the discovery and development of self-amplifying mRNA vaccines, and reviews how they might be used as a rapid response platform. The paper points out how future improvements in RNA vector design and non-viral delivery may lead to decreases in effective dose and increases in production capacity. The prospects for non-viral delivery of self-amplifying mRNA vaccines are very promising. Like other types of nucleic acid vaccines, these vaccines have the potential to draw on the positive attributes of live-attenuated vaccines while obviating many potential safety limitations. Hence, this approach could enable the concept of vaccines on demand as a rapid response to a real threat rather than the deployment of strategic stockpiles based on epidemiological predictions for possible threats.
Berecz, Bernadett; Zelenyánszki, Helga; Pólya, Sára; Tamás-Nyitrai, Cecília; Oszvald, Mária
Vaccines produced in plants have opened up new opportunities in vaccination. Among the various categories of vaccines, the recombinant vaccine is generally regarded as the most economical and safest type because it cannot cause disease and does not require large-scale cultivation of pathogens. Due to the low cost of their cultivation, plants may represent viable alternative platforms for producing subunit vaccines. Genetic engineering of plastids is the innovation of the last three decades and has numerous benefits when compared to nuclear transformation. Due to the high level of expression, oral vaccines produced in transplastomic plants do not have to be purified as they can be consumed raw, which, therefore, reduces the cost of preparation, transportation and handling of the vaccines. Oral vaccination also excludes the risk of other infections or contaminations, while compartmentation of the plant cell provides an excellent encapsulation to the antigen within the plastid. Herein we review the main biotechnological and immunological aspects of the progress achieved in the field of plastid derived edible vaccines during the last decade. As there is a public debate against genetically modified crops, the advantages and limitations of oral vaccines are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Lin, Ken; Roosinovich, Elena; Ma, Barbara; Hung, Chien-Fu
It is now well established that most cervical cancers are causally associated with HPV infection. This realization has led to efforts to control HPV-associated malignancy through prevention or treatment of HPV infection. Currently, commercially available HPV vaccines are not designed to control established HPV infection and associated premalignant and malignant lesions. To treat and eradicate pre-existing HPV infections and associated lesions which remain prevalent in the U.S. and worldwide, effective therapeutic HPV vaccines are needed. DNA vaccination has emerged as a particularly promising form of therapeutic HPV vaccines due to its safety, stability and ability to induce antigen-specific immunity. This review focuses on improving the potency of therapeutic HPV vaccines through modification of dendritic cells (DCs) by  increasing the number of antigen-expressing/antigen-loaded DCs,  improving HPV antigen expression, processing and presentation in DCs, and  enhancing DC and T cell interaction. Continued improvement in therapeutic HPV DNA vaccines may ultimately lead to an effective DNA vaccine for the treatment of HPV-associated malignancies. PMID:20066511
Maksiutov, R A; Gavrilova, E V; Shchelkunov, S N
The review gives data on the history of smallpox vaccination and shows the high topicality of designing the current safe vaccines against orthopoxviruses. Four generations of live smallpox, protein subunit, and DNA vaccines are considered. Analysis of the data published leads to the conclusion that it is promising to use the up-to-date generations of safe smallpox subunit or DNA vaccines for mass primary immunization with possible further revaccination with classical live vaccine.
Knight-Jones, T.J.D.; Bulut, A.N.; Gubbins, S.; Stärk, K.D.C.; Pfeiffer, D.U.; Sumption, K.J.; Paton, D.J.
Foot-and-mouth disease (FMD) is present in much of Turkey and its control is largely based on vaccination. The arrival of the FMD Asia-1 serotype in Turkey in 2011 caused particular concern, spreading rapidly westwards across the country towards the FMD free European Union. With no prior natural immunity, control of spread would rely heavily on vaccination. Unlike human vaccines, field protection is rarely evaluated directly for FMD vaccines. Between September 2011 and July 2012 we performed four retrospective outbreak investigations to assess the vaccine effectiveness (VE) of FMD Asia-1 vaccines in Turkey. Vaccine effectiveness is defined as the reduction in risk in vaccinated compared to unvaccinated individuals with similar virus exposure in the field. The four investigations included 12 villages and 1230 cattle >4 months of age. One investigation assessed the FMD Asia-1 Shamir vaccine, the other three evaluated the recently introduced FMD Asia-1 TUR 11 vaccine made using a field isolate of the FMD Asia-1 Sindh-08 lineage that had recently entered Turkey. After adjustment for confounding, the TUR 11 vaccine provided moderate protection against both clinical disease VE = 69% [95% CI: 50%–81%] and infection VE = 63% [95% CI: 29%–81%]. However, protection was variable with some herds with high vaccine coverage still experiencing high disease incidence. Some of this variability will be the result of the variation in virus challenge and immunity that occurs under field conditions. In the outbreak investigated there was no evidence that the Asia-1 Shamir vaccine provided adequate protection against clinical FMD with an incidence of 89% in single vaccinated cattle and 69% in those vaccinated two to five times. Based on these effectiveness estimates, vaccination alone is unlikely to produce the high levels of herd immunity needed to control FMD without additional control measures. PMID:24530150
Sep 7, 2011 ... The ability to make a large variety of virus-like particles. (VLPs) has been successfully achieved in the BEVS/ insect cell system (Aucoin et al., 2007). Examples include the adeno-associated viral (AAV) particles (Sollerbrant et al., 2001), Nudaurelia capensis omega virus (NomegaV). (Maree et al., 2006) etc.
If you would like more information about how to print, save, and work with PDFs, Highwire Press provides a helpful Frequently Asked Questions about PDFs. Alternatively, you can download the PDF file directly to your computer, from where it can be opened using a PDF reader. To download the PDF, click the Download link ...
Munsick, Tristram R; Peck, Dannele E; Ritten, John P; Jones, Randall; Jones, Michelle; Miller, Myrna M
Recurring outbreaks of bluetongue virus in domestic sheep of the US Intermountain West have prompted questions about the economic benefits and costs of vaccinating individual flocks against bluetongue (BT) disease. We estimate the cost of a BT outbreak on a representative rangeland sheep operation in the Big Horn Basin of the state of Wyoming using enterprise budgets and stochastic simulation. The latter accounts for variability in disease severity and lamb price, as well as uncertainty about when an outbreak will occur. We then estimate the cost of purchasing and administering a BT vaccine. Finally, we calculate expected annual net benefit of vaccinating under various outbreak intervals. Expected annual net benefit is calculated for both a killed virus (KV) vaccine and modified-live virus vaccine, using an observed price of $0.32 per dose for modified-live and an estimated price of $1.20 per dose for KV. The modified-live vaccine's expected annual net benefit has a 100% chance of being positive for an outbreak interval of 5, 10, or 20 years, and a 77% chance of being positive for a 50-year interval. The KV vaccine's expected annual net benefit has a 97% chance of being positive for a 5-year outbreak interval, and a 42% chance of being positive for a 10-year interval. A KV vaccine is, therefore, unlikely to be economically attractive to producers in areas exposed less frequently to BT disease. A modified-live vaccine, however, requires rigorous authorization before legal use can occur in Wyoming. To date, no company has requested to manufacture a modified-live vaccine for commercial use in Wyoming. The KV vaccine poses less risk to sheep reproduction and less risk of unintentional spread, both of which facilitate approval for commercial production. Yet, our results show an economically consequential tradeoff between a KV vaccine's relative safety and higher cost. Unless the purchase price is reduced below our assumed $1.20 per dose, producer adoption of a KV
Haber, Gillian; Malow, Robert M; Zimet, Gregory D
In this editorial we address the controversies surrounding human papillomavirus (HPV) vaccine school-entry mandate legislation, but differentiate between the mandate debate and issues specific to the vaccine itself. Our goal is not to take a stand in favor of or opposed to mandates, but rather to critically examine the issues. We discuss the following arguments against HPV vaccine school-entry requirements: 1. The public health benefit of mandated HPV vaccination is not sufficient to warrant the intrusion on parental autonomy; 2. A vaccine that prevents a non-casually transmitted infection should not be mandated; 3. Opt-out provisions are inherently unfair to parents who oppose HPV vaccination; 4. Limited health care dollars should not be directed toward cervical cancer prevention; and 5. The vaccine is expensive and potential problems with supply suggest that mandates should not be implemented until insurance coverage and supply issues are resolved. Next, we critically evaluate the following critiques of HPV vaccination itself: 1. Giving girls HPV vaccine implies tacit consent to engage in sexual activity; 2. Giving girls this vaccine will confer a false sense of protection from sexually transmitted infections and will lead to sexual disinhibition; 3. Children already have too many vaccinations on the immunization schedule; 4. Long-term side effects of HPV vaccine are unknown; 5. The vaccine's enduring effectiveness is unknown and booster shots may be required; and 6. It is wrong to only target girls with HPV vaccine; boys should be vaccinated as well.
Oyarzún, Patricio; Kobe, Bostjan
Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.
Alphavirus vectors based on Semliki Forest virus, Sindbis virus, and Venezuelan equine encephalitis virus have been widely applied for vaccine development. Naked RNA replicons, recombinant viral particles, and layered DNA vectors have been subjected to immunization in preclinical animal models with antigens for viral targets and tumor antigens. Moreover, a limited number of clinical trials have been conducted in humans. Vaccination with alphavirus vectors has demonstrated efficient immune responses and has showed protection against challenges with lethal doses of virus and tumor cells, respectively. Moreover, vaccines have been developed against alphaviruses causing epidemics such as Chikungunya virus.
Nazerai, Loulieta; Bassi, Maria Rosaria; Uddbäck, Ida Elin Maria
the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo...... cytotoxicity of the elicited memory CD8+ T cells, as well as the potential of these cells to respond to secondary infections and confer protection. We further tested the impact of maternal immunity against our replication-deficient adenoviral vector during early life vaccination. Overall, our results indicate...
Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...
Kelso, John M
Most children with a history of penicillin allergy are labeled allergic and denied treatment with penicillin and sometimes other beta-lactam antibiotics. Most of these children never were or are no longer allergic to penicillin. Penicillin skin testing and oral challenge can identify patients who are not currently allergic, allowing them to be treated with penicillin. Children with egg allergy are often denied influenza vaccination, because the vaccine contains a small amount of egg protein. However, recent studies have demonstrated that children with even severe egg allergy can safely receive the vaccine, reducing their risk of the morbidity and mortality associated with influenza. Copyright © 2015 Elsevier Inc. All rights reserved.
Hansen, Morten; Met, O; Svane, I M
Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor...... in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....
Hansen, M; Met, Ö; Svane, I M
Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor...... to transiently affect in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....
Rose, Kathleen C
The Advisory Committee on Immunization Practices recommends that the Tdap, HPV, and meningitis vaccines be administered to youth beginning between the ages of 11 and 12. The school nurse, knowledgeable about vaccine schedules and the rationale for the schedules, is in a unique position to advocate for all adolescent vaccines and their timely administration through addressing parent-guardian concerns and supporting other healthcare providers in completing the adolescent vaccines. This article reviews current recommendations for adolescent vaccinations and the actions needed to improve vaccination rates with a focus on Human Papillomavirus vaccine, the vaccine with the lowest completion rates among this age group. Additionally, school nurses are introduced to Middle School Health Starts Here, a program for school nurses designed to address the whole child as students progress from 5th grade to middle school. Public policy issues including school mandates, along with possible barriers to vaccine completion in adolescents, are discussed.
Shinmyo, Atsuhiko; Kato, Ko
On the basis of developments in plant biotechnology, drug and vaccine production by higher plants can be added to microbial and animal cell culture processes. When genes encoding drug or vaccine formation under a suitable promoter are introduced into plants, these useful compounds can be economically produced from CO(2) and inorganic chemicals using sunlight. The merits and demerits of the plant process are discussed in this paper.
R. Salam, A. Aslam. S. A, Khan, K. Saeed1 and G. Saleem
Full Text Available This project was designed to compare two routes (intraocular and drinking water of vaccination against Newcastle disease in ten11s of protection against velogenic field isolate of Newcastle disease virus (NOV, The immune response and morphological changes in lymphoid organs (Harderian gland, bursa of fabricius and thymus of broilers were noted. The role of Harderian gland to generate local and humoral immunity in response to eye drop and drinking water vaccination against NOV was also evaluated. This experiment showed that ocular vaccination resulted in significantly high level of circulating antibodies as compared to drinking water vaccination, No histopathological changes were observed in Iymphow organs after Nov challenge in ocularly vaccinated birds. There were significantly (P<0.05 higher number of plasma cells in sections of Harderian gland after eye drop vaccination, It was concluded that ocular vaccination stimulated Harderian gland to produce strong local protective immunity in ocular as well as in oral mucosa
Antigenics is developing a therapeutic cancer vaccine based on heat-shock proteins (HSPs). The vaccine [HSPPC-96, Oncophage] is in a pivotal phase III clinical trial for renal cancer at 80 clinical sites worldwide. The trial is enrolling at least 500 patients who are randomised to receive surgical removal of the primary tumour followed by out-patient treatment with Oncophage((R)) or surgery only. This study was initiated on the basis of results from a pilot phase I/II study and preliminary results from a phase II study in patients with renal cell cancer. In October 2001, Oncophage was designated as a fast-track product by the Food and Drug Administration in the US for the treatment of renal cell carcinoma. Oncophage is in phase I/II trials in Italy for colorectal cancer (30 patients) and melanoma. The trials in Italy are being conducted at the Istituto dei Tumouri, Milan (in association with Sigma-Tau). Preliminary data from the phase II trial for melanoma was presented at the AACR-NCI-EORTC International Conference in Florida, USA, in October 2001. Oncophage is also in a phase I/II (42 patients) and a phase II trial (84 patients) in the US for renal cell cancer, a phase II trial in the US for non-Hodgkin's lymphoma (35 patients), a phase II trial in the US for sarcoma (20-35 patients), a phase I/II trial in the US for melanoma (36 patients), and phase I/II trials in Germany for gastric (30 patients) and pancreatic cancers. A pilot phase I trial in patients with pancreatic cancer began in the US in 1997 with 5 patients enrolled. In November 2000, Antigenics announced that this trial had been expanded to a phase I/II study which would now include survival as an endpoint and would enroll 5 additional patients. The US trials are being performed at Memorial Sloan-Kettering Cancer Center and the M.D. Anderson Cancer Center. The trials in Germany are being carried out at Johannes Gutenberg-University Hospital, Mainz. Oncophage is an autologous vaccine consisting of
vaccinated chicken showed the presence of antibody responses againsted the extract cell and whole cell antigens of either P. multocida BCC 2331 or DY2 local isolate as detected by ELISA. The antibody responses from vaccinated chicken against extra cellular antigens prepared from broth cultures of BCC 2331 and DY2 were detected only from vaccinated chicken with vaccine containing killed antigen of BCC 2331 and/or DY2 isolate. It is likely, the local isolate of P. multocida BCC 2331 and DY2 would be benefit for producing inactive fowl cholera vaccine use in Indonesia, but the protective antigen that enhances immune protection should be determined by means of immunoblotting techniques.
... caused by persistent infection and genital warts ( 22 ). Analyses of data from women participating in a clinical ... is to contact the insurance plan or the clinic. Most private insurance plans cover HPV vaccination. The ...
Vaccination with a synthetic glycoconjugate, in combination with the administration of an inhibitor that blocks capsular polysaccharide synthesis in bacteria, could offer an alternative route to combat bacterial infections.
González-Romo, Fernando; Picazo, Juan J
Recent and important advances in the fields of immunology, genomics, functional genomics, immunogenetics, immunogenomics, bioinformatics, microbiology, genetic engineering, systems biology, synthetic biochemistry, proteomics, metabolomics and nanotechnology, among others, have led to new approaches in the development of vaccines. The better identification of ideal epitopes, the strengthening of the immune response due to new adjuvants, and the search of new routes of vaccine administration, are good examples of advances that are already a reality and that will favour the development of more vaccines, their use in indicated population groups, or its production at a lower cost. There are currently more than 130 vaccines are under development against the more wished (malaria or HIV), difficult to get (CMV or RSV), severe re-emerging (Dengue or Ebola), increasing importance (Chagas disease or Leishmania), and nosocomial emerging (Clostridium difficile or Staphylococcus aureus) infectious diseases. Copyright © 2015. Published by Elsevier España, S.L.U.
Yu, Qinghua; Zhu, Liqi; Kang, Haihong; Yang, Qian
Traditional non-gastrointestinal vaccines can prevent effectively the invasion of pathogens; however, these vaccines are less effective against mucosal infections because there is not a sufficient immune response at the mucosa. Most pathogens invade via a mucosal pathway (oral, intranasal, or vaginal). It is widely accepted that Lactobacillus species play a critical role as commensals in the gastrointestinal (GI) tract. Their ability to survive in the digestive tract, their close association with the intestinal epithelium, their immunomodulatory properties and their safety even when consumed in large amounts make lactobacilli attractive candidates for live vehicles for the delivery of immunogens to the intestinal mucosa. The oral or intranasal administration of Lactobacillus-based vaccines is a promising method to control mucosal infection because these vaccines could induce strong humoral and cellular immune responses both in the blood and at mucosal sites.
Fact Sheet Hepatitis B Vaccination Protection Hepatitis B virus (HBV) is a pathogenic microorganism that can cause potentially life- threatening disease in humans. HBV infection is transmitted through exposure ...
WHO is now celebrating more than 30 years of freedom from smallpox. What was originally seen as a victory over an ancient scourge can now be viewed as an epidemiologically driven programme to overcome governmental inertia and under-achievement in delivering an off-patent vaccine. Though efforts are accelerating global vaccine use, a plea is made to push the world's governments to commit to universal childhood vaccination via a proposed new programme. The latter should begin by exploiting a long list of ever more affordable off-patent vaccines, vaccines that can virtually eliminate the bulk of the world's current vaccine-preventable disease burden.
Marieke van der Heiden
Full Text Available BackgroundPrevention of infectious diseases is of high priority in the rapidly aging population. Unfortunately, vaccine responses in the elderly are frequently diminished. Timely vaccination of middle-aged adults might improve the immune responses to vaccines, although knowledge on pathogen-specific immune responses and factors affecting these responses, in middle-aged adults is currently limited. We thus investigated the immune responses after vaccination with Zostavax consisting of live-attenuated varicella zoster virus (VZV.MethodsBlood samples were taken pre-, 14 days, 28 days, and 1 year after a primary VZV vaccination (Zostavax at middle age (N = 53, 50–65 years of age. VZV-specific IFNγ-producing cells were measured by ELISpot, activated T-cells by flow cytometry, antibody levels and cytokine responses by fluorescent bead-based multiplex immunoassays, and whole blood cellular kinetics by TruCOUNT analysis.ResultsRobust short-term enhancement of the VZV-specific IFNγ-producing cell numbers was observed post-vaccination in the middle-aged adults. Remarkably, long-term enhancement of VZV-specific IFNγ-producing cell numbers was induced only in participants with low numbers of VZV-specific pre-vaccination IFNγ-producing cells, who were significantly older. These participants also showed enhancement of VZV-specific activated CD4 T-cells, contrary to “exhausted” VZV-specific CD8 T-cells in participants with high numbers of VZV-specific pre-vaccination IFNγ-producing cells. Finally, a high CD4/CD8 T-cell ratio was associated with low numbers of pre-vaccination VZV-specific IFNγ-producing cells.ConclusionThese results suggest that adults in their early sixties, who showed a high CD4/CD8 T-cell ratio and low numbers of VZV-specific IFNγ-producing cells, benefit from VZV vaccination. This provides important knowledge on factors affecting VZV-specific immune responses in middle-aged adults as well as for strategies to
Wang, Ching-Min; Chen, Shou-Chien; Chen, Kow-Tong
Rotaviruses remain the major cause of childhood diarrheal disease worldwide and of diarrheal deaths of infants and children in developing countries. The huge burden of childhood rotavirus-related diarrhea in the world continues to drive the remarkable pace of vaccine development. Research articles were searched using terms "rotavirus" and "rotavirus vaccine" in MEDLINE and PubMed. Articles not published in the English language, articles without abstracts, and opinion articles were excluded from the review. After preliminary screening, all articles were reviewed and synthesized to provide an overview of current vaccines and vaccination programs. In this review of the global rotavirus vaccines and vaccination programs, the principles of rotavirus vaccine development and the efficacy of the currently licensed vaccines from both developed and developing countries were summarized. Rotavirus is a common cause of diarrhea in children in both developed and developing countries. Rotavirus vaccination is a cost-effective measure to prevent rotavirus diarrhea.
Orme, I M; McMurray, D N; Belisle, J T
Recent years have seen a renewed effort to develop new vaccines against tuberculosis. As a result, several promising avenues of research have developed, including the production of recombinant vaccines, auxotrophic vaccines, DNA vaccines and subunit vaccines. In this article we briefly review this work, as well as consider the pros and cons of the animal models needed to test these new vaccines. Screening to date has been carried out in mouse and guinea pig models, which have been used to obtain basic information such as the effect of the vaccine on bacterial load, and whether the vaccine can prevent or reduce lung pathology. The results to date lead us to be optimistic that new candidate vaccines could soon be considered for evaluation in clinical trials.
Santosham, Mathuram; Nelson, E Anthony S; Bresee, Joseph S
At the 2006 meeting of the Asian Pacific Pediatric Association (APPA), the Asia Pacific regional rotavirus community and international experts strongly recommended that rotavirus vaccines be used in National Immunization Programmes (NIP) in countries in Asia. Two rotavirus vaccine candidates are currently licensed and have been demonstrated to be safe, well tolerated and highly efficacious. Several additional vaccines are in the late stages of development. The conference participants agreed that decisions on the introduction of rotavirus vaccines may require additional disease burden data in some countries and that economic evaluations will help policymakers reach decisions on nationwide rotavirus vaccine implementation. Other potential issues that arise with vaccine implementation, for example, the concomitant use of rotavirus vaccines with other vaccines, were also discussed. Rotavirus vaccines have the potential to substantially reduce morbidity and mortality from rotavirus disease and impact children's health in Asia.
Worz, Chad; Martin, Caren McHenry; Travis, Catherine
Several vaccine-preventable diseases-influenza, pneumonia, herpes zoster, and pertussis-threaten the health of older adults in the United States. Both the costs associated with treating these diseases and the potential to increase morbidity and mortality are high for this patient population. Pharmacists and other health care professionals play a significant role in ensuring the elderly patient receives the recommended vaccines at the recommended intervals.
Nicol, A F; Andrade, C V; Russomano, F B; Rodrigues, L L S; Oliveira, N S; Provance, D W
Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.
Full Text Available Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.
Pruna, Dario; Balestri, Paolo; Zamponi, Nelia; Grosso, Salvatore; Gobbi, Giuseppe; Romeo, Antonino; Franzoni, Emilio; Osti, Maria; Capovilla, Giuseppe; Longhi, Riccardo; Verrotti, Alberto
Reports of childhood epilepsies in temporal association with vaccination have had a great impact on the acceptance of vaccination programs by health care providers, but little is known about this possible temporal association and about the types of seizures following vaccinations. For these reasons the Italian League Against Epilepsy (LICE), in collaboration with other Italian scientific societies, has decided to generate Guidelines on Vaccinations and Epilepsy. The aim of Guidelines on Vaccinations and Epilepsy is to present recent unequivocal evidence from published reports on the possible relationship between vaccines and epilepsy in order to provide information about contraindications and risks of vaccinations in patients with epilepsy. The following main issues have been addressed: (1) whether contraindications to vaccinations exist in patients with febrile convulsions, epilepsy, and/or epileptic encephalopathies; and (2) whether any vaccinations can cause febrile seizures, epilepsy, and/or epileptic encephalopathies. Diphtheria-tetanus-pertussis (DTP) vaccination and measles, mumps, and rubella vaccination (MMR) increase significantly the risk of febrile seizures. Recent observations and data about the relationships between vaccination and epileptic encephalopathy show that some cases of apparent vaccine-induced encephalopathy could in fact be caused by an inherent genetic defect with no causal relationship with vaccination. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.
Fragoso, Gladis; Hernández, Marisela; Cervantes-Torres, Jacquelynne; Ramírez-Aquino, Rubén; Chapula, Héctor; Villalobos, Nelly; Segura-Velázquez, René; Figueroa, Alfredo; Flores, Iván; Jiménez, Herminio; Adalid, Laura; Rosas, Gabriela; Galvez, Luis; Pezzat, Elias; Monreal-Escalante, Elizabeth; Rosales-Mendoza, Sergio; Vazquez, Luis G; Sciutto, Edda
Transgenic papaya callus lines expressing the components of the S3Pvac vaccine constitute a stable platform to produce an oral vaccine against cysticercosis caused by Taenia solium or T. crassiceps. The development of effective delivery systems to cope with the reduced immunogenicity of new subunit vaccines is a priority in vaccinology. Herein, experimental evidence supporting a papaya-based platform to produce needle-free, recombinant, highly immunogenic vaccines is shown. Papaya (Carica papaya) callus lines were previously engineered by particle bombardment to express the three protective peptides of the S3Pvac anti-cysticercosis vaccine (KETc7, KETc12, KETc1). Calli were propagated in vitro, and a stable integration and expression of the target genes has been maintained, as confirmed by PCR, qRT-PCR, and HPLC. These results point papaya calli as a suitable platform for long-term transgenic expression of the vaccine peptides. The previously demonstrated protective immunogenic efficacy of S3Pvac-papaya orally administered to mice is herein confirmed in a wider dose-range and formulated with different delivery vehicles, adequate for oral vaccination. This protection is accompanied by an increase in anti-S3Pvac antibody titers and a delayed hypersensitivity response against the vaccine. A significant increase in CD4+ and CD8+ lymphocyte proliferation was induced in vitro by each vaccine peptide in mice immunized with the lowest dose of S3Pvac papaya (0.56 ng of the three peptides in 0.1 µg of papaya callus total protein per mouse). In pigs, the obliged intermediate host for Taenia solium, S3Pvac papaya was also immunogenic when orally administered in a two-log dose range. Vaccinated pigs significantly increased anti-vaccine antibodies and mononuclear cell proliferation. Overall, the oral immunogenicity of this stable S3Pvac-papaya vaccine in mice and pigs, not requiring additional adjuvants, supports the interest in papaya callus as a useful platform for plant
... is the best person to ask about which vaccines your child should get. How often does my child need a vaccination? Depending on the vaccine, your child may need only one shot. Other vaccines may ...
Unlike other segments of international food production, finfish aquaculture has so far not been associated with major food scandals. However, because of increased focus on food safety, the seafood industry and associated businesses have to respond to and document all aspects related to their products and processes. Consumers have a right to know, and need knowledge and information to be able to make qualified choices. In aquaculture good management and environmental attention is essential for both product quality and economic sustainability. One of the main challenges in all farming activities is efficient fish health management, which is crucial for maintaining and further developing the industry. In all biological production, and also in aquaculture, diseases have been, are, and will continue to present a challenge. When dealing with disease incidents, environmental, ethical, biological and economic issues must be taken into account. In animal health management there is a common understanding that prevention is better than treatment, so also in aquaculture. In many segments of industrial fish farming, vaccines have proved a good management tool to control diseases and to reduce both mortality and the use of chemotherapeutics. As seen in a recent Norwegian consumer survey, this might unfortunately look somewhat different from a consumer point of view. The perception of vaccines as foreign substances, visible vaccine lesions or pigment, words about genetically produced vaccines, and a general lack of knowledge may fuel scepticism. Even when experts are giving good and well-documented information, consumers still stick to their original perception of food, including seafood. Given this background, this papers discusses the aquaculture industry's priorities regarding vaccines and vaccination strategies, and its information policy towards the customer.
Pentel, Paul R.; LeSage, Mark G.
Clinical trials of nicotine vaccines suggest that they can enhance smoking cessation rates but do not reliably produce the consistently high serum antibody concentrations required. A wide array of next-generation strategies are being evaluated to enhance vaccine efficacy or provide antibody through other mechanisms. Protein conjugate vaccines may be improved by modifications of hapten or linker design or by optimizing hapten density. Conjugating hapten to viruslike particles or disrupted virus may allow exploitation of naturally occurring viral features associated with high immunogenicity. Conjugates that utilize different linker positions on nicotine can function as independent immunogens, so that using them in combination generates higher antibody concentrations than can be produced by a single immunogen. Nanoparticle vaccines, consisting of hapten, T cell help peptides, and adjuvants attached to a liposome or synthetic scaffold, are in the early stages of development. Nanoparticle vaccines offer the possibility of obtaining precise and consistent control of vaccine component stoichiometry and spacing and immunogen size and shape. Passive transfer of nicotine-specific monoclonal antibodies offers a greater control of antibody dose, the ability to give very high doses, and an immediate onset of action but is expensive and has a shorter duration of action than vaccines. Viral vector-mediated transfer of genes for antibody production can elicit high levels of antibody expression in animals and may present an alternative to vaccination or passive immunization if the long-term safety of this approach is confirmed. Next-generation immunotherapies are likely to be substantially more effective than first-generation vaccines. PMID:24484987
Arrazola, M Pilar; Serrano, Almudena; López-Vélez, Rogelio
Traveler's vaccination is one of the key strategies for the prevention of infectious diseases during international travel. The risk of acquiring an infectious disease is determined in each case by the characteristics of the traveler and the travel, so the pre-departure medical advice of the traveler must be individualized. The World Health Organization classifies travelerś vaccines into three groups. - Vaccines for routine use in national immunization programs: Haemophilus influenzae type b, hepatitis B, polio, measles-mumps-rubella, tetanus-diphtheria-whooping a cough, and chickenpox. - Vaccinations required by law in certain countries before to enter them: yellow fever, meningococcal disease and poliomyelitis. - Vaccines recommended depending on the circumstances: cholera, japanese encephalitis, tick-borne encephalitis, meningococcal disease, typhoid fever, influenza, hepatitis A, hepatitis B, rabies and BCG. This review is intended to introduce the reader to the field of international vaccination. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Boigard, Hélène; Alimova, Alexandra; Martin, George R.; Katz, Al; Gottlieb, Paul
The newly emerged mosquito-borne Zika virus poses a major public challenge due to its ability to cause significant birth defects and neurological disorders. The impact of sexual transmission is unclear but raises further concerns about virus dissemination. No specific treatment or vaccine is currently available, thus the development of a safe and effective vaccine is paramount. Here we describe a novel strategy to assemble Zika virus-like particles (VLPs) by co-expressing the structural (CprME) and non-structural (NS2B/NS3) proteins, and demonstrate their effectiveness as vaccines. VLPs are produced in a suspension culture of mammalian cells and self-assembled into particles closely resembling Zika viruses as shown by electron microscopy studies. We tested various VLP vaccines and compared them to analogous compositions of an inactivated Zika virus (In-ZIKV) used as a reference. VLP immunizations elicited high titers of antibodies, as did the In-ZIKV controls. However, in mice the VLP vaccine stimulated significantly higher virus neutralizing antibody titers than comparable formulations of the In-ZIKV vaccine. The serum neutralizing activity elicited by the VLP vaccine was enhanced using a higher VLP dose and with the addition of an adjuvant, reaching neutralizing titers greater than those detected in the serum of a patient who recovered from a Zika infection in Brazil in 2015. Discrepancies in neutralization levels between the VLP vaccine and the In-ZIKV suggest that chemical inactivation has deleterious effects on neutralizing epitopes within the E protein. This along with the inability of a VLP vaccine to cause infection makes it a preferable candidate for vaccine development. PMID:28481898
Full Text Available Dengue viruses (DENV are the most important mosquito transmitted viral pathogens infecting humans. DENV infection produces a spectrum of disease, most commonly causing a self-limiting flu-like illness known as dengue fever; yet with increased frequency, manifesting as life-threatening dengue hemorrhagic fever (DHF. Waning cross-protective immunity from any of the four dengue serotypes may enhance subsequent infection with another heterologous serotype to increase the probability of DHF. Decades of effort to develop dengue vaccines are reaching the finishing line with multiple candidates in clinical trials. Nevertheless, concerns remain that imbalanced immunity, due to the prolonged prime-boost schedules currently used in clinical trials, could leave some vaccinees temporarily unprotected or with increased susceptibility to enhanced disease. Here we develop a DENV serotype 1 (DENV-1 DNA vaccine with the immunodominant cross-reactive B cell epitopes associated with immune enhancement removed. We compare wild-type (WT with this cross-reactivity reduced (CRR vaccine and demonstrate that both vaccines are equally protective against lethal homologous DENV-1 challenge. Under conditions mimicking natural exposure prior to acquiring protective immunity, WT vaccinated mice enhanced a normally sub-lethal heterologous DENV-2 infection resulting in DHF-like disease and 95% mortality in AG129 mice. However, CRR vaccinated mice exhibited redirected serotype-specific and protective immunity, and significantly reduced morbidity and mortality not differing from naïve mice. Thus, we demonstrate in an in vivo DENV disease model, that non-protective vaccine-induced immunity can prime vaccinees for enhanced DHF-like disease and that CRR DNA immunization significantly reduces this potential vaccine safety concern. The sculpting of immune memory by the modified vaccine and resulting redirection of humoral immunity provide insight into DENV vaccine induced immune
Assi, Tina-Marie; Rookkapan, Korngamon; Rajgopal, Jayant; Sornsrivichai, Vorasith; Brown, Shawn T; Welling, Joel S; Norman, Bryan A; Connor, Diana L; Chen, Sheng-I; Slayton, Rachel B; Laosiritaworn, Yongjua; Wateska, Angela R; Wisniewski, Stephen R; Lee, Bruce Y
When policymakers make decision about the target populations and timing of influenza vaccination, they may not consider the impact on the vaccine supply chains, which may in turn affect vaccine availability. Our goal is to explore the effects on the Thailand vaccine supply chain of introducing influenza vaccines and varying the target populations and immunization time-frames. We Utilized our custom-designed software HERMES (Highly Extensible Resource for Modeling Supply Chains), we developed a detailed, computational discrete-event simulation model of the Thailand's National Immunization Program (NIP) supply chain in Trang Province, Thailand. A suite of experiments simulated introducing influenza vaccines for different target populations and over different time-frames prior to and during the annual influenza season. Introducing influenza vaccines creates bottlenecks that reduce the availability of both influenza vaccines as well as the other NIP vaccines, with provincial to district transport capacity being the primary constraint. Even covering only 25% of the Advisory Committee on Immunization Practice-recommended population while administering the vaccine over six months hinders overall vaccine availability so that only 62% of arriving patients can receive vaccines. Increasing the target population from 25% to 100% progressively worsens these bottlenecks, while increasing influenza vaccination time-frame from 1 to 6 months decreases these bottlenecks. Since the choice of target populations for influenza vaccination and the time-frame to deliver this vaccine can substantially affect the flow of all vaccines, policy-makers may want to consider supply chain effects when choosing target populations for a vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.
Christensen, Hannah; Hickman, Matthew; Edmunds, W John; Trotter, Caroline L
Meningococcal disease remains an important cause of morbidity and mortality worldwide. The first broadly effective vaccine against group B disease (which causes considerable meningococcal disease in Europe, the Americas and Australasia) was licensed in the EU in January 2013; our objective was to estimate the potential impact of introducing such a vaccine in England. We developed two models to estimate the impact of introducing a new 'MenB' vaccine. The cohort model assumes the vaccine protects against disease only; the transmission dynamic model also allows the vaccine to protect against carriage (accounting for herd effects). We used these, and economic models, to estimate the case reduction and cost-effectiveness of a number of different vaccine strategies. We estimate 27% of meningococcal disease cases could be prevented over the lifetime of an English birth cohort by vaccinating infants at 2,3,4 and 12 months of age with a vaccine that prevents disease only; this strategy could be cost-effective at £9 per vaccine dose. Substantial reductions in disease (71%) can be produced after 10 years by routinely vaccinating infants in combination with a large-scale catch-up campaign, using a vaccine which protects against carriage as well as disease; this could be cost-effective at £17 per vaccine dose. New 'MenB' vaccines could substantially reduce disease in England and be cost-effective if competitively priced, particularly if the vaccines can prevent carriage as well as disease. These results are relevant to other countries, with a similar epidemiology to England, considering the introduction of a new 'MenB' vaccine. Copyright © 2013 Elsevier Ltd. All rights reserved.
Gullberg, Maria; Lohse, Louise; Bøtner, Anette
Foot-and-mouth disease (FMD) is one of the most economically important infectious diseases of production animals globally. Vaccination can help to control this disease, however, current vaccines are imperfect. They are made using chemically inactivated FMD virus (FMDV) that is produced in mammalian......-boost system, using reagents that can be generated outside of high-containment facilities, offers significant advantages to achieve control of FMD by vaccination....
Ness, T; Hengel, H
Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects.
Tsen, Shaw-Wei David; Donthi, Nisha; La, Victor; Hsieh, Wen-Han; Li, Yen-Der; Knoff, Jayne; Chen, Alexander; Wu, Tzyy-Choou; Hung, Chien-Fu; Achilefu, Samuel; Tsen, Kong-Thon
There is an urgent need for rapid methods to develop vaccines in response to emerging viral pathogens. Whole inactivated virus (WIV) vaccines represent an ideal strategy for this purpose; however, a universal method for producing safe and immunogenic inactivated vaccines is lacking. Conventional pathogen inactivation methods such as formalin, heat, ultraviolet light, and gamma rays cause structural alterations in vaccines that lead to reduced neutralizing antibody specificity, and in some cases, disastrous T helper type 2-mediated immune pathology. We have evaluated the potential of a visible ultrashort pulsed (USP) laser method to generate safe and immunogenic WIV vaccines without adjuvants. Specifically, we demonstrate that vaccination of mice with laser-inactivated H1N1 influenza virus at about a 10-fold lower dose than that required using conventional formalin-inactivated influenza vaccines results in protection against lethal H1N1 challenge in mice. The virus, inactivated by the USP laser irradiation, has been shown to retain its surface protein structure through hemagglutination assay. Unlike conventional inactivation methods, laser treatment did not generate carbonyl groups in protein, thereby reducing the risk of adverse vaccine-elicited T helper type 2 responses. Therefore, USP laser treatment is an attractive potential strategy to generate WIV vaccines with greater potency and safety than vaccines produced by current inactivation techniques.
possible to produce and considering that these viral agents were discovered in license the first product developed by using the new 19731 and 1965...Propagation of human hepatit s A virus great number of children, whereas the disease ranges in cell culture in vitro. Proc Soc Exp Biol Med 1979:160:213...long immun ity’. 10. Provost PJ. Hughes JN, Miller WJ. Giesa PA, Banker FS, Emini EA. t An inactivated hepatitis A viral vaccine of cell culture
Hampson, Alan W
Fears of a potential pandemic due to A(H5N1) viruses have focussed new attention on our current vaccines, their shortcomings, and concerns regarding global vaccine supply in a pandemic. The bulk of current vaccines are inactivated split virus vaccines produced from egg-grown virus and have only modest improvements compared with those first introduced over 60 years ago. Splitting, which was introduced some years ago to reduce reactogenicity, also reduces the immunogenicity of vaccines in immunologically naïve recipients. The A(H5N1) viruses have been found poorly immunogenic and present other challenges for vaccine producers which further exacerbate an already limited global production capacity. There have been some recent improvements in vaccine production methods and improvements to immunogenicity by the development of new adjuvants, however, these still fall short of providing timely supplies of vaccine for all in the face of a pandemic. New approaches to influenza vaccines which might fulfil the demands of a pandemic situation are under evaluation, however, these remain some distance from clinical reality and face significant regulatory hurdles.
Drolet, Mélanie; Laprise, Jean-François; Brotherton, Julia M L; Donovan, Basil; Fairley, Christopher K; Ali, Hammad; Bénard, Élodie; Martin, Dave; Brisson, Marc
We used transmission-dynamic modeling to estimate the added effectiveness of vaccinating multiple cohorts of females (12-26 years) in Australia compared with the theoretical introduction of routine-only (12-13 years) vaccination. Our results suggest that vaccinating multiple cohorts produced markedly faster direct/herd effects, and it added benefits that last for 20-70 years. Furthermore, the number needed to vaccinate to prevent 1 anogential warts (AGW) case or cervical cancer (CC) was similar for routine + catch-up (AGW = 9.9, CC = 678) and routine-only vaccination (AGW = 9.9, CC = 677), thus providing similar levels of efficiency per person vaccinated. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: firstname.lastname@example.org.
Sher, S A
The article deals with the history of vaccination against natural smallpox which is directly connected to the Imperial Moscow foster house which became one of smallpox vaccination centers in Russia of XIX century. In 1801, when variolations were substituted by more safe cowpox vaccinations, in Russia the first vaccination using the method of Jenner was made exactly in in the Imperial Moscow foster house. From 1805, the smallpox vaccination received the status of force of law, the Imperial Moscow foster house began to produce and to distribute the smallpox vaccine all over the country and apply the smallpox vaccination not only to its foster children but to all turned to and, besides that, to train the smallpox vaccination. In 1857, the Imperial Moscow foster house became the first establishment in Russia where the revaccination was applied. In 1980, the WHO proclaimed that the implementation of the global program of smallpox irradiation resulted in the natural smallpox elimination on Earth. The smallpox became the first communicable disease defeated due to mass vaccination. One third of Earth population was vaccinated by the Soviet vaccine, which originated mainly because of the activities of physicians of the Imperial Moscow foster house.
Full Text Available The present study evaluates the immune response mediated by vaccination with cell complexes composed of irradiated B16 tumor cells and mouse fibroblasts genetically modified to produce GM-CSF. The animals were vaccinated with free B16 cells or cell complexes. We employed two gene plasmid constructions: one high producer (pMok and a low producer (p2F. Tumor transplant was performed by injection of B16 tumor cells. Plasma levels of total IgG and its subtypes were measured by ELISA. Tumor volumes were measured and survival curves were obtained. The study resulted in a cell complex vaccine able to stimulate the immune system to produce specific anti-tumor membrane proteins (TMP IgG. In the groups vaccinated with cells transfected with the low producer plasmid, IgG production was higher when we used free B16 cell rather than cell complexes. Nonspecific autoimmune response caused by cell complex was not greater than that induced by the tumor cells alone. Groups vaccinated with B16 transfected with low producer plasmid reached a tumor growth delay of 92% (p ≤ 0.01. When vaccinated with cell complex, the best group was that transfected with high producer plasmid, reaching a tumor growth inhibition of 56% (p ≤ 0.05. Significant survival (40% was only observed in the groups vaccinated with free transfected B16 cells.
... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Pseudorabies Vaccine. 113.318 Section... Virus Vaccines § 113.318 Pseudorabies Vaccine. Pseudorabies Vaccine shall be prepared from virus-bearing... be used for preparing seeds for vaccine production. All serials of vaccine shall be prepared from the...
... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bluetongue Vaccine. 113.303 Section... Virus Vaccines § 113.303 Bluetongue Vaccine. Bluetongue Vaccine shall be prepared from virus-bearing... be used for preparing the seeds for vaccine production. All serials of vaccine shall be prepared from...
... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Measles Vaccine. 113.313 Section 113... Vaccines § 113.313 Measles Vaccine. Measles Vaccine shall be prepared from virus-bearing cell culture... for preparing the production seed virus for vaccine production. All serials of vaccine shall be...
Paran, Nir; Sutter, Gerd
Smallpox has been eradicated but stockpiles of the causative infectious agent, variola virus, have been maintained over decades. Today, the threat of accidental or intentional poxvirus release is accompanied by the fact that the existing licensed smallpox vaccines cause rare but severe adverse reactions yet are the only products with approved efficacy against smallpox. New safer vaccines and new strategies of immunization are to be developed to fit to a scenario of emergency smallpox vaccination. However, we still lack knowledge about the pathogen and the mechanisms involved in acquiring protective immunity. Here, we review the history of smallpox vaccines and recent achievements in the development of highly efficacious and safer vaccines and vaccine applications. These include i) assessment of adequate animal models to study pathogenesis and protective immunity, ii) characterization of the immunity elicited by next generation vaccines, and (iii) the investigation of the requirements for rapidly protective vaccination.
Emmanuel D. Jadhav
Full Text Available IntroductionThe resurgence of vaccine preventable diseases occurs more often among intentionally unvaccinated individuals, placing at direct risk young adults not caught up on vaccinations. The objectives of this study were to characterize the sociodemographic characteristics of young adults with and without vaccination waivers and identify their perceived benefits, barriers, and influencers of vaccination.MethodsYoung adults (n = 964 from a Midwestern rural university responded to a survey (fall 2015—spring 2016 designed to identify their perception toward vaccination. Instrument consistency was measured using the Cronbach α-scores. The Chi-square test was used to test any sociodemographic differences and Mann–Whitney U-tests results for differences between exempt and non-exempt students. Analysis occurred in spring 2017.ResultsA little over one-third of young adults with a vaccination waiver were not up to date on their vaccinations, and think that vaccinations can cause autism. The biggest identifiable benefit was effective control against disease. The surveyed young adults ranked the out of pocket cost associated with vaccination as the most important barrier and safe and easy to use vaccines as the most important influencer of vaccination.ConclusionYoung adults who have had a vaccination waiver appear to not be up to date on their vaccinations. Vaccine administration programs, such as university campus clinics, would benefit from addressing perceptions unique to young adults with and without a vaccine waiver. This would subsequently better provide young adults a second shot for getting appropriately caught up on vaccinations.
Silva, Ediane B; Dow, Steven W
Burkholderia mallei and Burkholderia pseudomallei are Gram-negative bacteria that cause glanders and melioidosis, respectively. Inhalational infection with either organism can result in severe and rapidly fatal pneumonia. Inoculation by the oral and cutaneous routes can also produce infection. Chronic infection may develop after recovery from acute infection with both agents, and control of infection with antibiotics requires prolonged treatment. Symptoms for both meliodosis and glanders are non-specific, making diagnosis difficult. B. pseudomallei can be located in the environment, but in the host, B. mallei and B. psedomallei are intracellular organisms, and infection results in similar immune responses to both agents. Effective early innate immune responses are critical to controlling the early phase of the infection. Innate immune signaling molecules such as TLR, NOD, MyD88, and pro-inflammatory cytokines such as IFN-γ and TNF-α play key roles in regulating control of infection. Neutrophils and monocytes are critical cells in the early infection for both microorganisms. Both monocytes and macrophages are necessary for limiting dissemination of B. pseudomallei. In contrast, the role of adaptive immune responses in controlling Burkholderia infection is less well understood. However, T cell responses are critical for vaccine protection from Burkholderia infection. At present, effective vaccines for prevention of glanders or meliodosis have not been developed, although recently development of Burkholderia vaccines has received renewed attention. This review will summarize current and past approaches to develop B. mallei and B. pseudomalllei vaccines, with emphasis on immune mechanisms of protection and the challenges facing the field. At present, immunization with live attenuated bacteria provides the most effective and durable immunity, and it is important therefore to understand the immune correlates of protection induced by live attenuated vaccines. Subunit
Silva, Ediane B.; Dow, Steven W.
Burkholderia mallei and Burkholderia pseudomallei are Gram-negative bacteria that cause glanders and melioidosis, respectively. Inhalational infection with either organism can result in severe and rapidly fatal pneumonia. Inoculation by the oral and cutaneous routes can also produce infection. Chronic infection may develop after recovery from acute infection with both agents, and control of infection with antibiotics requires prolonged treatment. Symptoms for both meliodosis and glanders are non-specific, making diagnosis difficult. B. pseudomallei can be located in the environment, but in the host, B. mallei and B. psedomallei are intracellular organisms, and infection results in similar immune responses to both agents. Effective early innate immune responses are critical to controlling the early phase of the infection. Innate immune signaling molecules such as TLR, NOD, MyD88, and pro-inflammatory cytokines such as IFN-γ and TNF-α play key roles in regulating control of infection. Neutrophils and monocytes are critical cells in the early infection for both microorganisms. Both monocytes and macrophages are necessary for limiting dissemination of B. pseudomallei. In contrast, the role of adaptive immune responses in controlling Burkholderia infection is less well understood. However, T cell responses are critical for vaccine protection from Burkholderia infection. At present, effective vaccines for prevention of glanders or meliodosis have not been developed, although recently development of Burkholderia vaccines has received renewed attention. This review will summarize current and past approaches to develop B. mallei and B. pseudomalllei vaccines, with emphasis on immune mechanisms of protection and the challenges facing the field. At present, immunization with live attenuated bacteria provides the most effective and durable immunity, and it is important therefore to understand the immune correlates of protection induced by live attenuated vaccines. Subunit
Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda
Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.
Okwor, Ifeoma; Uzonna, Jude
Despite a plethora of publications on the murine model of cutaneous leishmaniasis and their contribution to our understanding of the factors that regulate the development of CD4+ T cell immunity in vivo, there is still no effective vaccine against the human disease. While recovery from natural or experimental infection with Leishmania major, the causative agent of human cutaneous leishmaniasis, results in persistence of parasites at the primary infection site and the development of long-lasting immunity to reinfection, vaccination with killed parasites or recombinant proteins induces only short-term protection. The reasons for the difference in protective immunity following recovery from live infection and vaccination with heat-killed parasites are not known. This may in part be related to persistence of live parasites following healing of primary cutaneous lesions, because complete clearance of parasites leads to rapid loss of infection-induced immunity. Recent reports indicate that in addition to persistent parasites, IL-10-producing natural regulatory T cells may also play critical roles in the maintenance and loss of infection-induced immunity. This review focuses on current understanding of the factors that regulate the development, maintenance and loss of anti-Leishmania memory responses and highlights the role of persistent parasites and regulatory T cells in this process. Understanding these factors is crucial for designing effective vaccines and vaccination strategies against cutaneous leishmaniasis.
Nathan C Peters
Full Text Available Numerous experimental vaccines have been developed to protect against the cutaneous and visceral forms of leishmaniasis caused by infection with the obligate intracellular protozoan Leishmania, but a human vaccine still does not exist. Remarkably, the efficacy of anti-Leishmania vaccines has never been fully evaluated under experimental conditions following natural vector transmission by infected sand fly bite. The only immunization strategy known to protect humans against natural exposure is "leishmanization," in which viable L. major parasites are intentionally inoculated into a selected site in the skin. We employed mice with healed L. major infections to mimic leishmanization, and found tissue-seeking, cytokine-producing CD4+ T cells specific for Leishmania at the site of challenge by infected sand fly bite within 24 hours, and these mice were highly resistant to sand fly transmitted infection. In contrast, mice vaccinated with a killed vaccine comprised of autoclaved L. major antigen (ALM+CpG oligodeoxynucleotides that protected against needle inoculation of parasites, showed delayed expression of protective immunity and failed to protect against infected sand fly challenge. Two-photon intra-vital microscopy and flow cytometric analysis revealed that sand fly, but not needle challenge, resulted in the maintenance of a localized neutrophilic response at the inoculation site, and removal of neutrophils following vector transmission led to increased parasite-specific immune responses and promoted the efficacy of the killed vaccine. These observations identify the critical immunological factors influencing vaccine efficacy following natural transmission of Leishmania.
Peters, Nathan C; Kimblin, Nicola; Secundino, Nagila; Kamhawi, Shaden; Lawyer, Phillip; Sacks, David L
Numerous experimental vaccines have been developed to protect against the cutaneous and visceral forms of leishmaniasis caused by infection with the obligate intracellular protozoan Leishmania, but a human vaccine still does not exist. Remarkably, the efficacy of anti-Leishmania vaccines has never been fully evaluated under experimental conditions following natural vector transmission by infected sand fly bite. The only immunization strategy known to protect humans against natural exposure is "leishmanization," in which viable L. major parasites are intentionally inoculated into a selected site in the skin. We employed mice with healed L. major infections to mimic leishmanization, and found tissue-seeking, cytokine-producing CD4+ T cells specific for Leishmania at the site of challenge by infected sand fly bite within 24 hours, and these mice were highly resistant to sand fly transmitted infection. In contrast, mice vaccinated with a killed vaccine comprised of autoclaved L. major antigen (ALM)+CpG oligodeoxynucleotides that protected against needle inoculation of parasites, showed delayed expression of protective immunity and failed to protect against infected sand fly challenge. Two-photon intra-vital microscopy and flow cytometric analysis revealed that sand fly, but not needle challenge, resulted in the maintenance of a localized neutrophilic response at the inoculation site, and removal of neutrophils following vector transmission led to increased parasite-specific immune responses and promoted the efficacy of the killed vaccine. These observations identify the critical immunological factors influencing vaccine efficacy following natural transmission of Leishmania.
Nannei, Claudia; Chadwick, Christopher; Fatima, Hiba; Goldin, Shoshanna; Grubo, Myriam; Ganim, Alexandra
Through its Global Action Plan for Influenza Vaccines (GAP), the World Health Organization (WHO) in collaboration with the United States Department of Health and Human Services has produced a checklist to support policy-makers and influenza vaccine manufacturers in identifying key technological, political, financial, and logistical issues affecting the sustainability of influenza vaccine production. This checklist highlights actions in five key areas that are beneficial for establishing successful local vaccine manufacturing. These five areas comprise: (1) the policy environment and health-care systems; (2) surveillance systems and influenza evidence; (3) product development and manufacturing; (4) product approval and regulation; and (5) communication to support influenza vaccination. Incorporating the checklist into national vaccine production programmes has identified the policy gaps and next steps for countries involved in GAP's Technology Transfer Initiative. Lessons learnt from country experiences provide context and insight that complement the checklist's goal of simplifying the complexities of influenza prevention, preparedness, and vaccine manufacturing. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Chen, Hualan; Bu, Zhigao
Following the first detection of the highly pathogenic H5N1 avian influenza virus in sick geese in Guangdong Province in China in 1996, scientists began to develop vaccines in preparation for an avian influenza pandemic. An inactivated H5N2 vaccine was produced from a low pathogenic virus, A/turkey/England/N-28/73, and was used for buffer zone vaccination during H5N1 outbreaks in 2004 in China. We also generated a low pathogenic H5N1 reassortant virus (Re-1) that derives its HA and NA genes from the GS/GD/96 virus and six internal genes from the high-growth A/Puerto Rico/8/34 (PR8) virus using plasmid-based reverse genetics. The inactivated vaccine derived from the Re-1 strain could induce more than ten months of protective immunity in chickens after one-dose inoculation; most importantly, this vaccine is immunogenic for geese and ducks. We recently developed a Newcastle virus-vectored live vaccine that exhibits great promise for use in the field to prevent highly pathogenic avian influenza and Newcastle disease in chickens. Over 30 billion doses of these vaccines have been used in China and other countries, including Vietnam, Mongolia, and Egypt, and have played an important role in H5N1 avian influenza control in these countries.
de Menezes Martins, Reinaldo; Fernandes Leal, Maria da Luz; Homma, Akira
Yellow fever vaccine was considered one of the safest vaccines, but in recent years it was found that it could rarely cause invasive and disseminated disease in some otherwise healthy individuals, with high lethality. After extensive studies, although some risk factors have been identified, the real cause of causes of this serious adverse event are largely unknown, but findings point to individual host factors. Meningoencephalitis, once considered to happen only in children less than 6 months of age, has also been identified in older children and adults, but with good prognosis. Efforts are being made to develop a safer yellow fever vaccine, and an inactivated vaccine or a vaccine prepared with the vaccine virus envelope produced in plants are being tested. Even with serious and rare adverse events, yellow fever vaccine is the best way to avoid yellow fever, a disease of high lethality and should be used routinely in endemic areas, and on people from non-endemic areas that could be exposed, according to a careful risk-benefit analysis.
Ana M. Z. Gagliardi
refrigerated zoster vaccine versus frozen zoster vaccine; one study compared live zoster vaccine versus inactivated zoster vaccine and one study compared zoster vaccine versus pneumococcal polysaccharide vaccine (pneumo 23.Confirmed cases of herpes zoster were less frequent in patients who received the vaccine than in those who received a placebo: risk ratio (RR 0.49 (95% confidence interval (CI 0.43 to 0.56, with a risk difference (RD of 2%, and number needed to treat to benefit (NNTB of 50. Analyses according to age groups indicated a greater benefit in participants aged 60 to 69 years, RR 0.36 (95% CI 0.30 to 0.45 and in participants aged 70 years and over, RR 0.63 (95% CI 0.53 to 0.75. Vaccine-related systemic adverse effects were more frequent in the vaccinated group (RR 1.29, 95% CI 1.05 to 1.57, number needed to treat to harm (NNTH = 100. The pooled data risk ratio for adverse effects for participants with one or more inoculation site adverse effect was RR 4.51 (95% CI 2.35 to 8.68, and the NNTH was 2.8 (95% CI 2.3 to 3.4. Side effects were more frequent in younger (60 to 69 years than in older (70 years and over participants.AUTHORS' CONCLUSIONS:Herpes zoster vaccine is effective in preventing herpes zoster disease. Although vaccine benefits are larger in the younger age group (60 to 69 years, this is also the age group with more adverse events. In general, zoster vaccine is well tolerated; it produces few systemic adverse events and injection site adverse effects of mild to moderate intensity.
Turkey herpesvirus (HVT) has been widely used as a vaccine for Marek’s disease (MD) since the 1970s. Because HVT is a safe vaccine that is poorly sensitive to interference from maternally derived antibodies, it has seen rising use as a vector for vaccines developed for protection against other comm...
Introduction: Underutilization of vaccines still remains a challenge in many regions across the world. Ileje district is one of the districts in Tanzania with consistently low pentavalent vaccine uptake (69%) and with drop out of 15%. We determined the vaccination completion with regard to Oral Polio virus, Measles, Bacillus ...
Patricia J Gearhart
Full Text Available Antibodies stand between us and pathogens. Viruses mutate quickly to avoid detection, and antibodies mutate at similar rates to hunt them down. This death spiral is fueled by specialized proteins and error-prone polymerases that change DNA sequences. Here, we explore how B lymphocytes stay in the race by expressing activation-induced deaminase, which unleashes a tsunami of mutations in the immunoglobulin loci. This produces random DNA substitutions, followed by selection for the highest affinity antibodies. We may be able to manipulate the process to produce better antibodies by expanding the repertoire of specific B cells through successive vaccinations.
Gearhart, Patricia J; Castiblanco, Diana P; Russell Knode, Lisa M
Antibodies stand between us and pathogens. Viruses mutate quickly to avoid detection, and antibodies mutate at similar rates to hunt them down. This death spiral is fueled by specialized proteins and error-prone polymerases that change DNA sequences. Here, we explore how B lymphocytes stay in the race by expressing activation-induced deaminase, which unleashes a tsunami of mutations in the immunoglobulin loci. This produces random DNA substitutions, followed by selection for the highest affinity antibodies. We may be able to manipulate the process to produce better antibodies by expanding the repertoire of specific B cells through successive vaccinations.
... What's this? Submit Button Past Emails Is Your Adult Vaccination Record Current? Recommend on Facebook Tweet Share ... recreate it by looking at your medical history. Adult Vaccination is Important Every year thousands of adults ...
... Types Seasonal Avian Swine/Variant Pandemic Other Flu Vaccine Safety and Pregnancy Questions & Answers Language: English (US) ... allergic conditions. How is the safety of flu vaccines in pregnant women monitored? CDC and FDA conduct ...
US Fish and Wildlife Service, Department of the Interior — Proposal by the State of Wyoming, Wyoming Game and Fish Department, to vaccinate elk on the National Elk Refuge. The proposal provides a protocol for vaccinating elk...
Kirkwood, Carl D; Buttery, Jim
Rotavirus vaccines offer the best hope to reduce the toll of acute rotaviral gastroenteritis in both developed and developing countries. An association with intussusception (IS) led to the withdrawal of the first licensed rotavirus vaccine in the USA in 1999, forcing a re-evaluation of the safety profile of potentially lifesaving vaccines. Development of new rotavirus vaccine candidates has continued, with a bovine-human reassortant vaccine and an attenuated human monovalent vaccine commencing Phase III trials. Several other candidates are in early Phase I and II clinical trials. The creation of innovative funding strategies to support vaccine development and production, specifically in developing countries, aim to make vaccines available where rotavirus causes the greatest impact.
Maria Goretti P Fonseca
Full Text Available BACKGROUND: The AIDS epidemic in Brazil remains concentrated in populations with high vulnerability to HIV infection, and the development of an HIV vaccine could make an important contribution to prevention. This study modeled the HIV epidemic and estimated the potential impact of an HIV vaccine on the number of new infections, deaths due to AIDS and the number of people receiving ARV treatment, under various scenarios. METHODS AND FINDINGS: The historical HIV prevalence was modeled using Spectrum and projections were made from 2010 to 2050 to study the impact of an HIV vaccine with 40% to 70% efficacy, and 80% coverage of adult population, specific groups such as MSM, IDU, commercial sex workers and their partners, and 15 year olds. The possibility of disinhibition after vaccination, neglecting medium- and high-risk groups, and a disease-modifying vaccine were also considered. The number of new infections and deaths were reduced by 73% and 30%, respectively, by 2050, when 80% of adult population aged 15-49 was vaccinated with a 40% efficacy vaccine. Vaccinating medium- and high-risk groups reduced new infections by 52% and deaths by 21%. A vaccine with 70% efficacy produced a great decline in new infections and deaths. Neglecting medium- and high-risk population groups as well as disinhibition of vaccinated population reduced the impact or even increased the number of new infections. Disease-modifying vaccine also contributed to reducing AIDS deaths, the need for ART and new HIV infections. CONCLUSIONS: Even in a country with a concentrated epidemic and high levels of ARV coverage, such as Brazil, moderate efficacy vaccines as part of a comprehensive package of treatment and prevention could have a major impact on preventing new HIV infections and AIDS deaths, as well as reducing the number of people on ARV. Targeted vaccination strategies may be highly effective and cost-beneficial.
Beirne, Paul V; Hennessy, Sarah; Cadogan, Sharon L; Shiely, Frances; Fitzgerald, Tony; MacLeod, Fiona
Hypodermic needles of different sizes (gauges and lengths) can be used for vaccination procedures. The gauge (G) refers to the outside diameter of the needle tubing. The higher the gauge number, the smaller diameter of the needle (eg a 25 G needle is 0.5 mm in diameter and is narrower than a 23 G needle (0.6 mm)). Many vaccines are recommended for injection into muscle (intramuscularly), although some are delivered subcutaneously (under the skin) and intradermally (into skin). Choosing an appropriate length and gauge of a needle may be important to ensure that a vaccine is delivered to the appropriate site and produces the maximum immune response while causing the least possible harm. There are some conflicting guidelines regarding the lengths and gauges of needles that should be used for vaccination procedures in children and adolescents. To assess the effects of using needles of different lengths and gauges for administering vaccines to children and adolescents on vaccine immunogenicity (the ability of the vaccine to elicit an immune response), procedural pain, and other reactogenicity events (adverse events following vaccine administration). We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2014, Issue 10), MEDLINE and MEDLINE in Progress via Ovid (1947 to November 2014), EMBASE via Ovid (1974 to November 2014), and CINAHL via EBSCOhost (1982 to November 2014). We also searched reference lists of articles and textbooks, the proceedings of vaccine conferences, and three clinical trial registers. Randomised controlled trials evaluating the effects of using hypodermic needles of any gauge or length to administer any type of vaccine to people aged from birth to 24 years. Three review authors independently extracted trial data and assessed the risk of bias. We contacted trial authors for additional information. We rated the quality of evidence using the GRADE system. We included five trials involving 1350 participants. Data for the
Cherwonogrodzky, John W; Barabé, Nicole D; Grigat, Michelle L; Lee, William E; Poirier, Robert T; Jager, Scott J; Berger, Bradley J
A subunit vaccine candidate was produced from Brucella suis 145 (biovar 4; expressing both the A antigen of Brucella abortus and the M antigen of Brucella melitensis). The preparation consisted mostly of polysaccharide (PS; >90% [wt/wt]; both cell-associated PS and exo-PS were combined) and a small amount of protein (1 to 3%) with no apparent nucleic acids. Vaccinated mice were protected (these had a statistically significant reduction in bacterial colonization compared to that of unvaccinated controls) when challenged with representative strains of three Brucella species most pathogenic for humans, i.e., B. abortus, B. melitensis, and B. suis. As little as 1 ng of the vaccine, without added adjuvant, protected mice against B. suis 145 infection (5 × 10(5) CFU), and a single injection of 1 μg of this subunit vaccine protected mice from B. suis 145 challenge for at least 14 months. A single immunization induced a serum IgG response to Brucella antigens that remained elevated for up to 9 weeks. The use of heat (i.e., boiling-water bath, autoclaving) in the vaccine preparation showed that it was thermostable. This method also ensured safety and security. The vaccine produced was immunogenic and highly protective against multiple strains of Brucella and represents a promising candidate for further evaluation. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
This year, as usual, the Medical Service is helping to promote vaccination against seasonal influenza. Vaccination against seasonal flu is especially recommended for anyone who suffers from chronic pulmonary, cardio-vascular or kidney disease or diabetes, is recovering from a serious illness or major surgery, or is over 65 years of age. The flu virus is transmitted through the air and through contact with contaminated surfaces, so frequent hand-washing with soap and/or an antiseptic hand wash is of great importance. As soon as the first symptoms appear (fever above 38°, shivering, coughing, muscle and/or joint pains, generalised weakness), you are strongly recommended to stay at home to avoid spreading the virus. Anyone working on the CERN site who wishes to be vaccinated against seasonal flu should go to the Infirmary (Building 57, ground floor), with their dose of vaccine. The Medical Service will issue a prescription on the day of the vaccination for the purposes of reimbursement through UNIQA...
Postma, Maarten J; Standaert, Baudouin A
Performing a total health economic analysis of a vaccine newly introduced into the market today is a challenge when using the conventional cost-effectiveness analysis we normally apply on pharmaceutical products. There are many reasons for that, such as: the uncertainty in the total benefit (direct and indirect) to be measured in a population when using a cohort model; (1) appropriate rules about discounting the long-term impact of vaccines are absent jeopardizing therefore their value at the initial investment; (2) the presence of opposite contexts when introducing the vaccine in developed vs. the developing world with high benefits, low initial health care investment for the latter vs. marginal benefit and high cost for the former; with a corresponding paradox for the vaccine becoming very cost-effective in low income countries but rather medium in middle low to high middle income countries; (3) and the type of trial assessment for the newer vaccines is now often performed with immunogenicity reaction instead of clinical endpoints which still leaves questions on their real impact and their head-to-head comparison. (4.)
Excler, Jean-Louis; Robb, Merlin L; Kim, Jerome H
The development of a safe and effective preventive HIV-1 vaccine remains a public health priority. Despite scientific difficulties and disappointing results, HIV-1 vaccine clinical development has, for the first time, established proof-of-concept efficacy against HIV-1 acquisition and identified vaccine-associated immune correlates of risk. The correlate of risk analysis showed that IgG antibodies against the gp120 V2 loop correlated with decreased risk of HIV infection, while Env-specific IgA directly correlated with increased risk. The development of vaccine strategies such as improved envelope proteins formulated with potent adjuvants and DNA and vectors expressing mosaics, or conserved sequences, capable of eliciting greater breadth and depth of potentially relevant immune responses including neutralizing and non-neutralizing antibodies, CD4+ and CD8+ cell-mediated immune responses, mucosal immune responses, and immunological memory, is now proceeding quickly. Additional human efficacy trials combined with other prevention modalities along with sustained funding and international collaboration remain key to bring an HIV-1 vaccine to licensure. PMID:24637946
Del Giudice, Giuseppe; Weinberger, Birgit; Grubeck-Loebenstein, Beatrix
The aging of the human population is posing serious challenges to research and to public health authorities in order to prevent diseases that more frequently affect the elderly, a portion of the population that will increase more and more in the coming years. While some vaccines exist and are used in the elderly to effectively fight against some infections (e.g. influenza, pneumococci, varicella-zoster virus, diphtheria, and tetanus), still a lot of work remains to be done to better adapt these vaccines and to develop new ones for this age group. The prevention of infectious diseases affecting the elderly can be successful only through a holistic approach. This approach will aim at the following: (1) a deeper understanding of the mechanisms leading to the senescence of the immune system, (2) a better and broader use of vaccines recommended for the elderly, (3) the use of vaccines currently considered only for other age groups and (4) actively priming the population when they are immunological competent, before the physiological waning of immune responsiveness may affect the beneficial effects of vaccination. © 2014 S. Karger AG, Basel
Lee, Bruce Y; Wedlock, Patrick T; Haidari, Leila A; Elder, Kate; Potet, Julien; Manring, Rachel; Connor, Diana L; Spiker, Marie L; Bonner, Kimberly; Rangarajan, Arjun; Hunyh, Delphine; Brown, Shawn T
While our previous work has shown that replacing existing vaccines with thermostable vaccines can relieve bottlenecks in vaccine supply chains and thus increase vaccine availability, the question remains whether this benefit would outweigh the additional cost of thermostable formulations. Using HERMES simulation models of the vaccine supply chains for the Republic of Benin, the state of Bihar (India), and Niger, we simulated replacing different existing vaccines with thermostable formulations and determined the resulting clinical and economic impact. Costs measured included the costs of vaccines, logistics, and disease outcomes averted. Replacing a particular vaccine with a thermostable version yielded cost savings in many cases even when charging a price premium (two or three times the current vaccine price). For example, replacing the current pentavalent vaccine with a thermostable version without increasing the vaccine price saved from $366 to $10,945 per 100 members of the vaccine's target population. Doubling the vaccine price still resulted in cost savings that ranged from $300 to $10,706, and tripling the vaccine price resulted in cost savings from $234 to $10,468. As another example, a thermostable rotavirus vaccine (RV) at its current (year) price saved between $131 and $1065. Doubling and tripling the thermostable rotavirus price resulted in cost savings ranging from $102 to $936 and $73 to $808, respectively. Switching to thermostable formulations was highly cost-effective or cost-effective in most scenarios explored. Medical cost and productivity savings could outweigh even significant price premiums charged for thermostable formulations of vaccines, providing support for their use. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Paterson, Pauline; Meurice, François; Stanberry, Lawrence R; Glismann, Steffen; Rosenthal, Susan L; Larson, Heidi J
While most people vaccinate according to the recommended schedule, this success is challenged by individuals and groups who delay or refuse vaccines. The aim of this article is to review studies on vaccine hesitancy among healthcare providers (HCPs), and the influences of their own vaccine confidence and vaccination behaviour on their vaccination recommendations to others. The search strategy was developed in Medline and then adapted across several multidisciplinary mainstream databases including Embase Classic & Embase, and PschInfo. All foreign language articles were included if the abstract was available in English. A total of 185 articles were included in the literature review. 66% studied the vaccine hesitancy among HCPs, 17% analysed concerns, attitudes and/or behaviour of HCPs towards vaccinating others, and 9% were about evaluating intervention(s). Overall, knowledge about particular vaccines, their efficacy and safety, helped to build HCPs own confidence in vaccines and their willingness to recommend vaccines to others. The importance of societal endorsement and support from colleagues was also reported. In the face of emerging vaccine hesitancy, HCPs still remain the most trusted advisor and influencer of vaccination decisions. The capacity and confidence of HCPs, though, are stretched as they are faced with time constraints, increased workload and limited resources, and often have inadequate information or training support to address parents' questions. Overall, HCPs need more support to manage the quickly evolving vaccine environment as well as changing public, especially those who are reluctant or refuse vaccination. Some recommended strategies included strengthening trust between HCPs, health authorities and policymakers, through more shared involvement in the establishment of vaccine recommendations. Copyright Â© 2016. Published by Elsevier Ltd.
Julio Cesar Reina; Nubia Muñoz
At present two prophylactic human papilloma virus (HPV) vaccines are commercially available. The Tetravalent vaccine against infection with four VPH types (6, 11, 16, and 18) distributed in the national program in Colombia and the Bivalent vaccine against the VPH types 16 and 18, respectively. The efficacy and safety of both vaccines has periodically been assessed and they have been declared efficacious and safe by the health authorities of several countries and the Global Advisory Committee...
Colby, Lesley A.
Vaccine Brucella abortus strain RB51, unlike the wild strain 2308 and another vaccine strain (strain 19) does not induce anti-O-chain antibodies. An efficacious vaccine strain that fails to produce an O-chain and thus a lack of an anti-O-chain humoral response greatly simplifies identification of vaccinated versus field strain infected animals. The three primary objectives of this research were the following: 1) to develop a serological assay to detect anti-RB51 antibodies in vaccinated elk (...
Audonnet, J Ch; Lechenet, J; Verschuere, B
Veterinary vaccine research, development and production facilities must aim to improve animal welfare, respond to public concerns and meet regulatory requirements, while at the same time fulfilling their objective of producing evermore effective and safer vaccines. The use of animal experimentation for the development of new veterinary vaccines is inevitable, as no in vitro model can predict a candidate vaccine's ability to induce protection in the target species. Against the backdrop of ethical and regulatory constraints, constant progress is being made in creating the best possible conditions for animal experimentation. Keeping up to date with the constant changes in the field of animal ethics requires a particular effort on the part of the pharmaceutical industry, which must make careful changes to product registration documentation in accordance with each new development.
Craciun, Gabriela D.; Togoe, Iulian I.; Tudor, Laurentiu M.; Martin, Diana I.; Manaila, Elena N.; Ighigeanu, Daniel I.; Iacob, Nicusor I.; Oproiu, Constantin V.
A new biotechnology for obtaining a commercial vaccine that contains either Fusobacterium necrophorum (F.n.) exotoxins inactivated by accelerated electron beam (EB) and microwave (MW) irradiation, or exotoxins isolated from F.n. cultures irradiated with EB+MW, is presented. This vaccine is designed for prophylaxis of ruminant infectious pododermatitis (IP) produced by F.n. Also, the research results concerning the effects of combined chemical adjuvant and EB+MW irradiation on F.n. immune capacity are discussed. The vaccine's efficacy will be tested in ruminant farms in which IP evolves. It is expected that this new vaccine to offer a better protection, more than 60%, which is the best presently obtained result in ruminant farms.
Milstien, Julie B; Gaulé, Patrick; Kaddar, Miloud
This study, conducted by visits, interviews, and literature search, analyzes how vaccine manufacturers in Brazil and India access technologies for innovative vaccines: through collaborations with academia and research institutions, technology transfer agreements with multinational corporations, public sector, or developing country organizations, or by importation and finishing of bulk products. Each has advantages and disadvantages in terms of speed, market, and ability to independently produce the product. Most manufacturers visited are very concerned about avoiding patent infringement, which might result in undeveloped or delayed products because of a lack of mastery of the patent landscape. Disregarding the patent picture could also threaten the market of a potential product. Although it is too soon to assess the effects of TRIPS on vaccine technology access in Brazil and India, a good understanding of intellectual property management will be useful. A case study on development of a new combination vaccine illustrates these findings.
Labrique, Alain B; Sikder, Shegufta S; Krain, Lisa J; West, Keith P; Christian, Parul; Rashid, Mahbubur; Nelson, Kenrad E
Hepatitis E virus (HEV) is a major cause of illness and of death in the developing world and disproportionate cause of deaths among pregnant women. Although HEV vaccine trials, including trials conducted in populations in southern Asia, have shown candidate vaccines to be effective and well-tolerated, these vaccines have not yet been produced or made available to susceptible populations. Surveillance data collected during 2001-2007 from >110,000 pregnancies in a population of ≈650,000 women in rural Bangladesh suggest that acute hepatitis, most of it likely hepatitis E, is responsible for ≈9.8% of pregnancy-associated deaths. If these numbers are representative of southern Asia, as many as 10,500 maternal deaths each year in this region alone may be attributable to hepatitis E and could be prevented by using existing vaccines.
The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19 th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI) (1978) and then Universal Immunization Programme (UIP) (1985) were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts.
The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI) (1978) and then Universal Immunization Programme (UIP) (1985) were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts. PMID:24927336
Full Text Available The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19 th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI (1978 and then Universal Immunization Programme (UIP (1985 were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts.
Waterbeemd, van de B.; Wijffels, R.H.; Zomer, G.; Kaaijk, P.; Ruiterkamp, N.; Dobbelsteen, van den G.J.M.; Pol, van der L.A.
An improved detergent-free process has been developed to produce vaccine based on native outer membrane vesicles (NOMV) against Neisseria meningitidis serogroup B. Performance was evaluated with the NonaMen vaccine concept, which provides broad coverage based on nine distinct PorA antigens. Scalable
protection against infection (Robbins and Robbins, 198.t This work is aimed at developing, producing and testing typhoid fever vaccines with the ho:x- of finding a highly immunogenic vaccine that will give protection against typhoid fever. MATERIALS AND METHODS. Isolation and Characterization of Local Strains.
The Frederick National Laboratory for Cancer Research is producing another round of Zika vaccine for ongoing studies to determine the best delivery method and dosage. This will lay the groundwork for additional tests to see if the vaccine prevents i
Benedictus, Lindert; Bell, Charlotte R
INTRODUCTION: Bovine neonatal pancytopenia (BNP) is a hemorrhagic disease that emerged in calves across Europe in 2007. Its occurrence is attributed to immunization of the calf's mother with a vaccine produced using an allogeneic cell line. Vaccine-induced alloantibodies specific for
The Frederick National Laboratory for Cancer Research is producing another round of Zika vaccine for ongoing studies to determine the best delivery method and dosage. This will lay the groundwork for additional tests to see if the vaccine prevents i
... die from flu, and many more are hospitalized.Flu vaccine can:keep you from getting flu, make flu ... What is inactivated or recombinant influenza vaccine?A dose of flu vaccine is recommended every flu season. Children 6 months through 8 years of age may need two ...
This paper seeks to critically review a traditional objection to preventive medicine (which I call here the 'prevention problem'). The prevention problem is a concern about the supposedly inequitable distribution of benefits and risks of harm resulting from preventive medicine's focus on population-based interventions. This objection is potentially applicable to preventive vaccination programmes and could be used to argue that such programmes are unethical. I explore the structure of the prevention problem by focusing upon two different types of vaccination (therapeutic vaccination and preventive vaccination). I argue that the 'prevention problem' cannot be fairly applied to the case of preventive vaccination because such programmes do not just focus upon benefits at the level of populations (as is claimed by the prevention problem). Most such preventive vaccination programmes explicitly seek to create and maintain herd protection. I argue that herd protection is an important public good which is a benefit shared by all individuals in the relevant population. This fact can then be used to block the 'prevention problem' argument in relation to preventive vaccination programmes. I conclude by suggesting that whilst the future development and use of therapeutic vaccines does raise some interesting ethical issues, any ethical objections to prophylactic vaccination on the basis of the 'prevention problem' will not be overcome through the substitution of therapeutic vaccines for preventive vaccines; indeed, the 'prevention problem' fails on its own terms in relation to preventive vaccination programmes.
Danchin, M H; Costa-Pinto, J; Attwell, K; Willaby, H; Wiley, K; Hoq, M; Leask, J; Perrett, K P; O'Keefe, Jacinta; Giles, M L; Marshall, H
Maternal and childhood vaccine decision-making begins prenatally. Amongst pregnant Australian women we aimed to ascertain vaccine information received, maternal immunisation uptake and attitudes and concerns regarding childhood vaccination. We also aimed to determine any correlation between a) intentions and concerns regarding childhood vaccination, (b) concerns about pregnancy vaccination, (c) socioeconomic status (SES) and (d) uptake of influenza and pertussis vaccines during pregnancy and routine vaccines during childhood. Women attending public antenatal clinics were recruited in three Australian states. Surveys were completed on iPads. Follow-up phone surveys were done three to six months post delivery, and infant vaccination status obtained via the Australian Childhood Immunisation Register (ACIR). Between October 2015 and March 2016, 975 (82%) of 1184 mothers consented and 406 (42%) agreed to a follow up survey, post delivery. First-time mothers (445; 49%) had significantly more vaccine concerns in pregnancy and only 73% had made a decision about childhood vaccination compared to 89% of mothers with existing children (p-valueeducation and communication on childhood and maternal vaccines, delivered by midwives and obstetricians in the Australian public hospital system, may reduce vaccine hesitancy for all mothers in pregnancy and post delivery, particularly first-time mothers. Copyright © 2017 Elsevier Ltd. All rights reserved.
Dec 4, 2009 ... of the major binding proteins, and reported that this vaccine could induce mucosal and cellular immunity, and neutralize antibody to various isolates of HIV. These exploratory studies may have implications for viral vaccines. Intranasal delivery of vaccines poses two major challenges: the first is accurate and ...
Baker, Jeffrey P.
The controversy regarding the once widely used mercury-containing preservative thimerosal in childhood vaccines has raised many historical questions that have not been adequately explored. Why was this preservative incorporated in the first place? Was there any real evidence that it caused harm? And how did thimerosal become linked in the public mind to the “autism epidemic”? I examine the origins of the thimerosal controversy and their legacy for the debate that has followed. More specifically, I explore the parallel histories of three factors that converged to create the crisis: vaccine preservatives, mercury poisoning, and autism. An understanding of this history provides important lessons for physicians and policymakers seeking to preserve the public’s trust in the nation’s vaccine system. PMID:18172138
As every year, the Medical Service is taking part in the campaign to promote vaccination against seasonal influenza. Vaccination against seasonal influenza is especially recommended for people suffering from chronic lung, cardio-vascular or kidney conditions or diabetes, for those recovering from a serious illness or surgical operation and for everyone over the age of 65. The influenza virus is transmitted by air and contact with contaminated surfaces, hence the importance of washing hands regularly with soap and / or disinfection using a hydro-alcoholic solution. From the onset of symptoms (fever> 38°, chills, cough, muscle aches and / or joint pain, fatigue) you are strongly recommended to stay at home to avoid spreading the virus. In the present context of the influenza A (H1N1) pandemic, it is important to dissociate these two illnesses and emphasise that the two viruses and the vaccines used to combat them are quite different and that protection against one will not pr...
Holst, Peter Johannes; Bassi, Maria Rosaria; Thomsen, Allan Randrup
DNA vaccines are versatile and safe, but limited immunogenicity has prevented their use in the clinical setting. Experimentally, immunogenicity may be enhanced by the use of new delivery technologies, by coadministration of cytokines and pathogen-associated molecular patterns, or by fusion...... of antigens into molecular domains that enhance antigen presentation. More specifically, the immunogenicity of DNA vaccines may benefit from increased protein synthesis, increased T-cell help and MHC class I presentation, and the addition of a range of specific cytokines and pathogen-associated molecular...... patterns that increase activation of the innate immune system. Importantly, viral-vectored vaccines that act through the induction of one or more of these factors also may benefit from cytokine coadministration and increased antigen presentation. In order to increase immunogenicity to the level achieved...
Geels, Mark J; Imoukhuede, Egeruan B; Imbault, Nathalie; van Schooten, Harry; McWade, Terry; Troye-Blomberg, Marita; Dobbelaer, Roland; Craig, Alister G; Leroy, Odile
For over 10 years, the European Vaccine Initiative (EVI; European Malaria Vaccine Initiative until 2009) has contributed to the development of 24 malaria candidate vaccine antigens with 13 vaccine candidates being advanced into Phase I clinical trials, two of which have been transitioned for further clinical development in sub-Saharan Africa. Since its inception the EVI organization has operated as a funding agency, but with a clear service-oriented strategy. The scientific successes and difficulties encountered during these years and how these efforts have led to standardization and harmonization in vaccine development through large-scale European consortia are discussed. In the future, the EVI will remain instrumental in the pharmaceutical and clinical development of vaccines against 'diseases of poverty' with a continued focus on malaria. EVI will continue to focus on funding and managing preclinical evaluation up to Phase I/II clinical trials and strengthening the vaccine-development infrastructure in Europe, albeit with a global orientation.
Curto, Alessandro; Duranti, Silvy; Van de Vooren, Katelijne; Garattini, Livio
This paper gives an overview, in the era of regionalization, of vaccination planning and vaccine price management in the Italian National Health Service. In particular, we analyse the current National Vaccination Plan (NVP) and end with two "case studies" of the latest entries in the Italian vaccination calendar, comparing HPV and PCV vaccines, the most expensive ones in Italy at present. The present NVP put an end to the long period without official documents for vaccination planning, mainly reflecting the controversial relationships between the national and regional tiers. However, this document is not really useful for planning from the health professionals' point of view, lacking epidemiological information. Thorough systematic assessment of the new, expensive vaccines is becoming a real priority in the light of current financial difficulties. In this perspective, the two examples discussed have given different results so far, starting from a heterogeneous situation of potential market competition.
Kumar, Rajiv; Engwerda, Christian
Leishmaniasis is a parasitic disease that encompasses a range of clinical manifestations affecting people in tropical and subtropical regions of the world. Epidemiological and experimental data indicate that protection from disease can be achieved in most people. In addition, we know how the host immune system must respond to infection in order to control parasite growth. However, there is still no vaccine for use in humans. Here, we review our understanding of host immunity following Leishmania infection and also discuss recent advances in the development of vaccines to prevent leishmaniasis, highlighting a new promising approach that targets the parasite hemoglobin receptor.
Foroughi-Parvar, Faeze; Hatam, Gholamreza
Leishmania infantum is the obligatory intracellular parasite of mammalian macrophages and causes zoonotic visceral leishmaniasis (ZVL). The presence of infected dogs as the main reservoir host of ZVL is regarded as the most important potential risk for human infection. Thus the prevention of canine visceral leishmaniasis (CVL) is essential to stop the current increase of the Mediterranean visceral leishmaniasis. Recently considerable advances in achieving protective immunization of dogs and several important attempts for achieving an effective vaccine against CVL lead to attracting the scientists trust in its important role for eradication of ZVL. This paper highlights the recent advances in vaccination against canine visceral leishmaniasis from 2007 until now.
Kennedy, Richard B; Ovsyannikova, Inna; Poland, Gregory A
Few diseases can match the enormous impact that smallpox has had on mankind. Its influence can be seen in the earliest recorded histories of ancient civilizations in Egypt and Mesopotamia. With fatality rates up to 30%, smallpox left its survivors with extensive scarring and other serious sequelae. It is estimated that smallpox killed 500 million people in the 19th and 20th centuries. Given the ongoing concerns regarding the use of variola as a biological weapon, this review will focus on the licensed vaccines as well as current research into next-generation vaccines to protect against smallpox and other poxviruses.
Full Text Available Leishmania infantum is the obligatory intracellular parasite of mammalian macrophages and causes zoonotic visceral leishmaniasis (ZVL. The presence of infected dogs as the main reservoir host of ZVL is regarded as the most important potential risk for human infection. Thus the prevention of canine visceral leishmaniasis (CVL is essential to stop the current increase of the Mediterranean visceral leishmaniasis. Recently considerable advances in achieving protective immunization of dogs and several important attempts for achieving an effective vaccine against CVL lead to attracting the scientists trust in its important role for eradication of ZVL. This paper highlights the recent advances in vaccination against canine visceral leishmaniasis from 2007 until now.
Church, Sarah E.; Jensen, Shawn M.; Twitty, Chris; Bahjat, Keith; Hu, Hong-Ming; Urba, Walter J.; Fox, Bernard A.
Few immunotherapists would accept the concept of a single vaccination inducing a therapeutic anti-cancer immune response in a patient with advanced cancer. But what is the evidence to support the “more-is-better” approach of multiple vaccinations? Since we are unaware of trials comparing the effect of a single vaccine versus multiple vaccinations on patient outcome, we considered that an anti-cancer immune response might provide a surrogate measure of the effectiveness of vaccination strategies. Since few large trials include immunological monitoring, the majority of information is gleaned from smaller trials in which an evaluation of immune responses to vaccine or tumor, before and at one or more times following the first vaccine was performed. In some studies there is convincing evidence that repeated administration of a specific vaccine can augment the immune response to antigens contained in the vaccine. In other settings multiple vaccinations can significantly reduce the immune response to one or more targets. Results from three large adjuvant vaccine studies support the potential detrimental effect of multiple vaccinations as clinical outcomes in the control arms were significantly better than that for treatment groups. Recent research has provided insights into mechanisms that are likely responsible for the reduced responses in the studies noted above, but supporting evidence from clinical specimens is generally lacking. Interpretation of these results is further complicated by the possibility that the dominant immune response may evolve to recognize epitopes not present in the vaccine. Nonetheless, the FDA-approval of the first therapeutic cancer vaccine and recent developments from preclinical models and clinical trials provide a substantial basis for optimism and a critical evaluation of cancer vaccine strategies. PMID:21952289
Saitoh, Akihiko; Aizawa, Yuta
Intradermal (ID) vaccination induces a more potent immune response and requires lower vaccine doses as compared with standard vaccination routes. To deliver ID vaccines effectively and consistently, an ID delivery device has been developed and is commercially available for adults. The clinical application of ID vaccines for infants and children is much anticipated because children receive several vaccines, on multiple occasions, during infancy and childhood. However, experience with ID vaccin...
Ediane Batista Silva
Full Text Available B. mallei and B. pseudomallei are Gram-negative bacteria that cause glanders and melioidosis, respectively. Inhalational infection with either organism can result in severe and rapidly fatal pneumonia. Inoculation by the oral and cutaneous routes can also produce infection. chronic infection develops after recovery from acute infection with both agents, and control of infection with antibiotics requires prolonged treatment. Symptoms for both meliodosis and glanders are non-specific, making diagnosis difficult.B. pseudomallei can be located in the environment, but in the host, B. mallei and B. psedomallei are intracellular organisms. Thefection results in similar immune responses to both agents. Effective early innate immune responses are critical to controlling the early phase of the infection. Innate immune signaling molecules such as TLR, NOD, MyD88 and pro-inflammatory cytokines such as IFN- and TNF-α play key roles in regulating control of infection. Neutrophils and monocytes are critical cells in the early infection for these microorganisms. Both monocytes and macrophages are necessary for limiting dissemination of B. pseudomallei. In contrast, the role of adaptive immune responses in controlling Burkholderia infection is less well understood. However, T cell responses are critical for vaccine protection from Burkholderia infection. At present, effective vaccines for prevention of glanders or meliodosis have not been developed, although recently progress of Burkholderia vaccines has received renewed attention.This review will summarize current and past approaches to develop Burkholderia mallei and pseudomalllei vaccines, with emphasis on immune mechanisms of protection and the challenges facing the field. At present, immunization with live attenuated bacteria provides the most effective and durable immunity, and it is important therefore to understand the immune correlates of protection induced by live attenuated vaccines.
Berman, Stephen; Giffin, Robert B
Despite the great promise of immunization and recent progress in immunizing children throughout the developing world, a global crisis in vaccine R&D, supply and delivery is faced. This article reviews how the global US6 billion dollars vaccine market is structured and its attractiveness to vaccine suppliers, the international two-tiered pricing system in which high-income countries generate about 82% of vaccine revenues but represent only 12% of the doses, the impact of schedule divergence as high-income and developing countries introduce different vaccines, the role of the US government, and possible approaches to ameliorate the crisis.
Wong, Yun-Ling; Sampson, Samantha; Germishuizen, Willem Andreas; Goonesekera, Sunali; Caponetti, Giovanni; Sadoff, Jerry; Bloom, Barry R.; Edwards, David
With the increasing incidence of tuberculosis and drug resistant disease in developing countries due to HIV/AIDS, there is a need for vaccines that are more effective than the present bacillus Calmette–Guérin (BCG) vaccine. We demonstrate that BCG vaccine can be dried without traditional freezing and maintained with remarkable refrigerated and room-temperature stability for months through spray drying. Studies with a model Mycobacterium (Mycobacterium smegmatis) revealed that by removing salts and cryoprotectant (e.g., glycerol) from bacterial suspensions, the significant osmotic pressures that are normally produced on bacterial membranes through droplet drying can be reduced sufficiently to minimize loss of viability on drying by up to 2 orders of magnitude. By placing the bacteria in a matrix of leucine, high-yield, free-flowing, “vial-fillable” powders of bacteria (including M. smegmatis and M. bovis BCG) can be produced. These powders show relatively minor losses of activity after maintenance at 4°C and 25°C up to and beyond 4 months. Comparisons with lyophilized material prepared both with the same formulation and with a commercial formulation reveal that the spray-dried BCG has better overall viability on drying. PMID:17299039
Al-Zahrani, Sharifa; Zaric, Marija; McCrudden, Cian; Scott, Chris; Kissenpfennig, Adrien; Donnelly, Ryan F
Breaching the skin's stratum corneum barrier raises the possibility of the administration of vaccines, gene vectors, antibodies and even nanoparticles, all of which have at least their initial effect on populations of skin cells. Intradermal vaccine delivery holds enormous potential for improved therapeutic outcomes for patients, particularly those in the developing world. Various vaccine-delivery strategies have been employed, which are discussed in this review. The importance of cutaneous immunobiology on the effect produced by microneedle-mediated intradermal vaccination is also discussed. Microneedle-mediated vaccines hold enormous potential for patient benefit. However, in order for microneedle vaccine strategies to fulfill their potential, the proportion of an immune response that is due to the local action of delivered vaccines on skin antigen-presenting cells, and what is due to a systemic effect from vaccines reaching the systemic circulation, must be determined. Moreover, industry will need to invest significantly in new equipment and instrumentation in order to mass-produce microneedle vaccines consistently. Finally, microneedles will need to demonstrate consistent dose delivery across patient groups and match this to reliable immune responses before they will replace tried-and-tested needle-and-syringe-based approaches.
Helps, Catherine; Leask, Julie; Barclay, Lesley
Despite strong evidence confirming vaccination is safe and effective, some parents choose not to vaccinate their children. In 2016, the Australian Government introduced legislation strengthening links between vaccination compliance and some government payments. We interviewed thirty-one non-vaccinating parents about the impacts of this policy. Data analysis produced three key themes: 'questioning policy integrity', 'minimising impact' and 'holding my ground'. Affected parents offset reduced income by removing children from early childhood learning, reducing work commitments, moving residence to reduce living costs and accessing informal childcare arrangements. Parents reported a greater commitment to their decision not to vaccinate and an increased desire to maintain control over health choices for their children including an unprecedented willingness to become involved in protest action. Our study identifies why financial penalties have not been an effective policy measure for this sample of non-vaccinating parents, an understanding which may assist in the development of future legislation.
Jørgensen, Louise von Gersdorff; Kania, Per Walter; Rasmussen, Karina Juhl
responses of vaccinated trout (subunit vaccine) were raised against one neurohypophysial n-terminal domain protein #10 of three recombinant proteins, whereas the benchmark vaccine group showed specific antibody production against all three recombinant proteins. The immunogenic parasite protein #10 may......The protective effect in rainbow trout (Oncorhynchus mykiss) of an experimental subunit vaccine targeting antigens in the parasite Ichthyophthirius multifiliis has been evaluated and compared to effects elicited by a classical parasite homogenate vaccine. Three recombinant parasite proteins (two...... produced in E. coli and one in insect cells) were combined and injected i.p., and subsequently, protection and antibody responses were analysed. Both the experimental and the benchmark vaccine induced partial but significant protection against I. multifiliis when compared to control fish. Specific antibody...
Full Text Available In our research four live attenuated vaccines against avian infectious bursitis (two inland produced and two imported were tested: Biavac, Biaromvac-Pa, Gumboro Vaccine Nobilis 228e and Live Virus Vaccine Tablets Gumboro, M.B. Strain. The research was made in production conditions on 44,400 broiler chickens maintained in industrial system and raised on bedding and in batteries. The broilers were kept in four poultry houses, each of them representing an experimental group. We mention that vaccines were administered only one time. Vaccines efficiency was assessed by immunoenzymatic test. In that purpose, for each poultry house, 20 broilers were isolated and identified by a tibial ring, their immune response being followed between 5 and 42 days of age. Analyzing the results about individual antibodies titer during the experiment, the significant differences were observed both in poultries and phases. The best results were obtained using Live Virus Vaccine Tablets Gumboro, M.B. strain.
Nicholas, Robin A J; Ayling, Roger D; Stipkovits, Laszlo P
A single dose of vaccine for Mycoplasma bovis pneumonia, inactivated with saponin, was inoculated subcutaneously into 3-4 week-old calves. The calves were challenged 3 weeks later with a virulent strain of M. bovis on two occasions within 24h using the aerosol route. The calves were monitored for clinical signs and serological responses then post mortemed 3 weeks after challenge. The vaccine was shown to be highly immunogenic in calves and did not cause adverse effects. Vaccinated calves showed few clinical signs while all unvaccinated calves developed signs of pneumonia. There was a significant decrease in body weight gain in unvaccinated calves compared to vaccinates and a significant increase in lung lesions and rectal temperatures in unvaccinated calves. The vaccine also reduced the spread of M. bovis to internal organs. In conclusion the M. bovis vaccine produced a significant level of protection against a large virulent challenge.
Kerwat, Klaus; Goedecke, Marcel; Wulf, Hinnerk
Vaccinations are among the most efficient and important preventive medical procedures. Modern vaccines are well tolerated. In Germany there are no longer laws for mandatory vaccinations, either for the general public or for medical personnel. Vaccinations are now merely "officially recommended" by the top health authorities on the basis of recommendations from the Standing Committee on Vaccinations (STIKO) of the Robert Koch Institute (RKI) according to § 20 para 3 of the Protection against Infection law (IfSG). The management of vaccine damage due to officially recommended vaccinations is guaranteed by the Federal States. Whereas vaccinations in childhood are generally considered to be a matter of course, the willingness to accept them decreases markedly with increasing age. In the medical sector vaccinations against, for example, hepatitis B are well accepted while other vaccinations against, for example, whooping cough or influenza are not considered to be so important. The fact that vaccinations, besides offering protection for the medical personnel, may also serve to protect the patients entrusted to medical care from nosocomial infections is often ignored. © Georg Thieme Verlag Stuttgart · New York.
Vaccine refusal harms and risks harming innocent bystanders. People are not entitled to harm innocents or to impose deadly risks on others, so in these cases there is nothing to be said for the right to refuse vaccination. Compulsory vaccination is therefore justified because non-vaccination can rightly be prohibited, just as other kinds of harmful and risky conduct are rightly prohibited. I develop an analogy to random gunfire to illustrate this point. Vaccine refusal, I argue, is morally similar to firing a weapon into the air and endangering innocent bystanders. By re-framing vaccine refusal as harmful and reckless conduct my aim is to shift the focus of the vaccine debate from non-vaccinators' religious and refusal rights to everyone else's rights against being infected with contagious illnesses. Religious freedom and rights of informed consent do not entitle non-vaccinators to harm innocent bystanders, and so coercive vaccination requirements are permissible for the sake of the potential victims of the anti-vaccine movement.
Kimman, T G
Vaccines against Aujeszky's disease are not only used to prevent the clinical consequences of a field infection, but also to support eradication of the virus. The current Aujeszky's disease vaccines (ADV) protect against severe clinical signs of disease and they reduce but usually do not prevent virus multiplication and excretion or the establishment of latency after infection. Vaccines also limit virus multiplication after reactivation. The efficacy of vaccination is reduced by passively acquired maternal antibodies. The mechanisms that afford immunity to the virus are only poorly understood. No simple parameters for immunity are therefore available. The European Pharmacopoeia formulates requirements for inactivated and live ADV vaccines for parenteral use. The vaccines must be safe; they must not induce local or systemic reactions; they must not be transmitted to unvaccinated pigs; they must not be transmitted by semen and across the placenta; the attenuation must be irreversible (live vaccines); the inactivation must be complete (inactivated vaccines); they must prevent mortality and limit growth retardation after challenge infection; the vaccine must not contain contaminating micro-organisms and viruses. No requirements have been formulated with regard to reduction of excretion of challenge virus after experimental infection, efficacy in pigs with maternal antibodies, reproducibility of efficacy studies, reduction of virus transmission under field conditions, the presence of a serological marker, safety for other species, and safety and efficacy of intranasally administered vaccines. Future developments should be directed to the development and evaluation of ADV vaccines that are able to limit transmission of the virus.
Knight-Jones, T. J. D.; Edmond, K.; Gubbins, S.; Paton, D. J.
Despite the universal importance of vaccines, approaches to human and veterinary vaccine evaluation differ markedly. For human vaccines, vaccine efficacy is the proportion of vaccinated individuals protected by the vaccine against a defined outcome under ideal conditions, whereas for veterinary vaccines the term is used for a range of measures of vaccine protection. The evaluation of vaccine effectiveness, vaccine protection assessed under routine programme conditions, is largely limited to human vaccines. Challenge studies under controlled conditions and sero-conversion studies are widely used when evaluating veterinary vaccines, whereas human vaccines are generally evaluated in terms of protection against natural challenge assessed in trials or post-marketing observational studies. Although challenge studies provide a standardized platform on which to compare different vaccines, they do not capture the variation that occurs under field conditions. Field studies of vaccine effectiveness are needed to assess the performance of a vaccination programme. However, if vaccination is performed without central co-ordination, as is often the case for veterinary vaccines, evaluation will be limited. This paper reviews approaches to veterinary vaccine evaluation in comparison to evaluation methods used for human vaccines. Foot-and-mouth disease has been used to illustrate the veterinary approach. Recommendations are made for standardization of terminology and for rigorous evaluation of veterinary vaccines. PMID:24741009
Legutki, Joseph Barten; Johnston, Stephen Albert
The development of new vaccines would be greatly facilitated by having effective methods to predict vaccine performance. Such methods could also be helpful in monitoring individual vaccine responses to existing vaccines. We have developed "immunosignaturing" as a simple, comprehensive, chip-based method to display the antibody diversity in an individual on peptide arrays. Here we examined whether this technology could be used to develop correlates for predicting vaccine effectiveness. By using a mouse influenza infection, we show that the immunosignaturing of a natural infection can be used to discriminate a protective from nonprotective vaccine. Further, we demonstrate that an immunosignature can determine which mice receiving the same vaccine will survive. Finally, we show that the peptides comprising the correlate signatures of protection can be used to identify possible epitopes in the influenza virus proteome that are correlates of protection.
Debbink, Kari; Lindesmith, Lisa C.; Baric, Ralph S.
Noroviruses represent the most important cause of acute gastroenteritis worldwide; however, currently no licensed vaccine exists. Widespread vaccination that minimizes overall norovirus disease burden would benefit the entire population, but targeted vaccination of specific populations such as healthcare workers may further mitigate the risk of severe disease and death in vulnerable populations. While a few obstacles hinder the rapid development of efficacious vaccines, human trials for virus-like particle (VLP)-based vaccines show promise in both immune response and protection studies, with availability of vaccines being targeted over the next 5–10 years. Ongoing work including identification of important norovirus capsid antigenic sites, development of improved model systems, and continued studies in humans will allow improvement of future vaccines. In the meantime, a better understanding of norovirus disease course and transmission patterns can aid healthcare workers as they take steps to protect high-risk populations such as the elderly and immunocompromised individuals from chronic and severe disease. PMID:24585561
Zhang, Jianfeng; Tarbet, E Bart; Toro, Haroldo; Tang, De-chu C
The disease-fighting power of vaccines has been a public health bonanza credited with the worldwide reduction of mortality and morbidity. The goal to further amplify its power by boosting vaccine coverage requires the development of a new generation of rapid-response vaccines that can be mass produced at low costs and mass administered by nonmedical personnel. The new vaccines also have to be endowed with a higher safety margin than that of conventional vaccines. The nonreplicating adenovirus-vectored vaccine holds promise in boosting vaccine coverage because the vector can be rapidly manufactured in serum-free suspension cells in response to a surge in demand, and noninvasively administered by nasal spray into human subjects in compliance with evolutionary medicine. In contrast to parenteral injection, noninvasive mucosal vaccination minimizes systemic inflammation. Moreover, pre-existing adenovirus immunity does not interfere appreciably with the potency of an adenovirus-vectored nasal vaccine. Nasal administration of adenovirus vectors encoding pathogen antigens is not only fear-free and painless, but also confers rapid and sustained protection against mucosal pathogens as a drug-vaccine duo since adenovirus particles alone without transgene expression can induce an anti-influenza state in the airway. In addition to human vaccination, animals can also be mass immunized by this class of vectored vaccines.
Campins Martí, Magda
Pneumococcal infections are a significant cause of morbidity and mortality, and are one of the 10 leading causes of death worldwide. Children under 2 years have a higher incidence rate, followed by adults over 64 years. The main risk group are individuals with immunodeficiency, and those with anatomical or functional asplenia, but can also affect immunocompetent persons with certain chronic diseases. Significant progress has been made in the last 10 years in the prevention of these infections. Until a few years ago, only the 23-valent non-conjugate pneumococcal vaccine was available. Its results were controversial in terms of efficacy and effectiveness, and with serious limitations on the type of immune response induced. The current possibility of using the 13-valent conjugate vaccine in adults has led to greater expectations in improving the prevention of pneumococcal disease in these age groups. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Jespersen, Sanne; Hønge, Bo Langhoff; Medina, Candida
Vaccination scars in HIV infected patients – does vaccinia vaccination confer protection against HIV?......Vaccination scars in HIV infected patients – does vaccinia vaccination confer protection against HIV?...
Larson, Heidi J; Cooper, Louis Z; Eskola, Juhani; Katz, Samuel L; Ratzan, Scott
Vaccines--often lauded as one of the greatest public health interventions--are losing public confidence. Some vaccine experts have referred to this decline in confidence as a crisis. We discuss some of the characteristics of the changing global environment that are contributing to increased public questioning of vaccines, and outline some of the specific determinants of public trust. Public decision making related to vaccine acceptance is neither driven by scientific nor economic evidence alone, but is also driven by a mix of psychological, sociocultural, and political factors, all of which need to be understood and taken into account by policy and other decision makers. Public trust in vaccines is highly variable and building trust depends on understanding perceptions of vaccines and vaccine risks, historical experiences, religious or political affiliations, and socioeconomic status. Although provision of accurate, scientifically based evidence on the risk-benefit ratios of vaccines is crucial, it is not enough to redress the gap between current levels of public confidence in vaccines and levels of trust needed to ensure adequate and sustained vaccine coverage. We call for more research not just on individual determinants of public trust, but on what mix of factors are most likely to sustain public trust. The vaccine community demands rigorous evidence on vaccine efficacy and safety and technical and operational feasibility when introducing a new vaccine, but has been negligent in demanding equally rigorous research to understand the psychological, social, and political factors that affect public trust in vaccines. Copyright © 2011 Elsevier Ltd. All rights reserved.
Het vaccin dat de kip moet beschermen tegen de bacterie Campylobacter werkt in het laboratorium. Dat wil bacterioloog Jaap Wagenaar wel kwijt. Wanneer het er komt en zelfs of het er komt, daarover laat Wagenaar zich niet uit. "Het is een hele klus om het immuunsysteem van kippen effectief op te
In this podcast for kids, the Kidtastics talk about the importance of vaccines and how they work. Created: 4/23/2013 by Centers for Disease Control and Prevention (CDC). Date Released: 4/23/2013.
Jos, Plateau State, Nigeria. E-Mail: j email@example.com. COMMON VACCINE PREVENTABLE. DISEASES: Chicken pox. Hepatitis A. Hepatitis В. Influenza ... ally reversed economic and social development in several countries. Current prevention efforts - including condom education, clean needle distribution, peer ...
Saadatian-Elahi, M.; Aaby, P.; Shann, F.; Netea, M.G.; Levy, O.; Louis, J.; Picot, V.; Greenberg, M.; Warren, W.
The heterologous or non-specific effects (NSEs) of vaccines, at times defined as "off-target effects" suggest that they can affect the immune response to organisms other than their pathogen-specific intended purpose. These NSEs have been the subject of clinical, immunological and epidemiological
Zavrel, Erik; Herreid, Clyde Freeman
This case study is centered upon the recent debate concerning the decision by Texas Governor Rick Perry to mandate the compulsory vaccination of girls in the Texas public school system against the human papillomavirus (HPV) prior to entering the sixth grade. The interrupted case method is particularly appropriate for this subject with the case…
Malaria is a major economic and public health problem in mainly sub-Saharan Africa. Globally 300-500 million new infections occur each year with 1-3 million fatal cases in particular young children. The most effective way to reduce disease and death from infectious diseases is to vaccinate
Decavac® (as a combination product containing Diphtheria, Tetanus Toxoids) ... Tenivac® (as a combination product containing Diphtheria, Tetanus Toxoids) ... Why get vaccinated?Tetanus and diphtheria are very serious diseases. They ... United States today, but people who do become infected often have severe ...
Human papillomavirus causes viral-dependent cancers, including cervical, anal, vulvar, penile, vaginal, and oropharyngeal, and condyloma acuminata. In the last decade, HPV prophylactic vaccine has been developed and spread worldwide after many large-scale clinical studies. These studies demonstrate significant clinical efficacy for prevention of HPV16/18/6/11-related diseases. In particular, prevention of cervical cancer should be the most important role in the world. In Japan, incidence of cervical cancer does not increase, but the peak of age of the patients at 2005 is 25-45 years old and became 20 years younger than that at 1985. The current two HPV vaccines can prevent the infection of HPV16/18 among high-risk HPVs and will provide a significant impact especially on young-age onset cervical cancer. Furthermore, quadrivalent HPV vaccine, Gardasil, has shown population impact that is decrease of patients with condyloma acuminate in several countries. The clinical efficacy seems to be convincing. Here HPV vaccine will be reviewed based on the literatures.
Hicks, D J; Fooks, A R; Johnson, N
The development of vaccines that prevent rabies has a long and distinguished history, with the earliest preceding modern understanding of viruses and the mechanisms of immune protection against disease. The correct application of inactivated tissue culture-derived vaccines is highly effective at preventing the development of rabies, and very few failures are recorded. Furthermore, oral and parenteral vaccination is possible for wildlife, companion animals and livestock, again using inactivated tissue culture-derived virus. However, rabies remains endemic in many regions of the world and causes thousands of human deaths annually. There also remain no means of prophylaxis for rabies once the virus enters the central nervous system (CNS). One reason for this is the poor immune response within the CNS to infection with rabies virus (RABV). New approaches to vaccination using modified rabies viruses that express components of the innate immune system are being applied to this problem. Preliminary reports suggest that direct inoculation of such viruses could trigger an effective anti-viral response and prevent a fatal outcome from RABV infection. © 2012 Crown copyright. Clinical and Experimental Immunology © 2012 British Society for Immunology.
Giachini, M; Pierleoni, F
Even though the reduction of caries-incidence in developed countries, its increasing has been observed nowadays. The use of a vaccine was object of many researches, going under modifications and evaluations during years. Wallace and McCollum showed the chance to induce experimental cavities, while Clarke and McIntosh were the first underlining the roll of S. mutans and Lactobacilli as efforts of the pathology. Williams was the first working with humans and Zinner and Fitzgerald continued. So since Bowen the research tried to build a vaccine made of single bacterial molecules with antigenic power. We can count about a large number of targets, like: the Ag I/II, the glucosyltransferase enzyme (GTF), the glucan-binding-protein (GBP), the destranase, the fruttosyltransferase and the glucans. Among the substances used to obtain a vaccine cacao revealed its capacity against bacteria able to develop cavities, thanks to its cariostatic and anti-glucosyltransferase activity due to polyphenols, that we can find in green tea too. It's also interesting a technique that gives passive antibodies like cow's milk, but in particular the one of a monoclonal antibody made with biotechnology of plants: the Guy's 13. It does not show substantial differences in comparison with the human Ig and it's able to prevent the installation of micro-organism and to reduce cavities in adult patients already infected. For the setting-up of a vaccine, however, only studies, comparison and research will be able to show precise instruments of defence.
The use of vaccination to control bovine viral diarrhea virus (BVDV) infections presents exceptional challenges due to the nature of the virus, the unique interaction of the virus with the immune system, and its ability to establish persistent infections. The lack of proof reading function during th...
Infections with the influenza virus and Streptococcus pneumoniae are associated with considerable morbidity and ... for Disease Control and Prevention, Atlanta, Georgia; CNS = central nervous system; COPD = chronic .... During delivery and storage, the vaccine should be kept at. 2 - gcC in cold chain, and stored in the ...
Postma, Maarten J.; Standaert, Baudouin A.
Performing a total health economic analysis of a vaccine newly introduced into the market today is a challenge when using the conventional cost-effectiveness analysis we normally apply on pharmaceutical products. There are many reasons for that, such as: the uncertainty in the total benefit (direct
Frederiksen, J. L.; Topsøe Mailand, M.
An association between certain vaccinations and onset or relapse of multiple sclerosis (MS) has been debated. Based on PubMed, we made a thorough literature review and included all relevant studies, 51 on MS and 15 on optic neuritis (ON). Case studies were excluded. With the exception of a live...
McLean, Kenneth A; Goldin, Shoshanna; Nannei, Claudia; Sparrow, Erin; Torelli, Guido
A global shortage and inequitable access to influenza vaccines has been cause for concern for developing countries who face dire consequences in the event of a pandemic. The Global Action Plan for Influenza Vaccines (GAP) was launched in 2006 to increase global capacity for influenza vaccine production to address these concerns. It is widely recognized that well-developed infrastructure to produce seasonal influenza vaccines leads to increased capacity to produce pandemic influenza vaccines. This article summarizes the results of a survey administered to 44 manufacturers to assess their production capacity for seasonal influenza and pandemic influenza vaccine production. When the GAP was launched in 2006, global production capacity for seasonal and pandemic vaccines was estimated to be 500million and 1.5billion doses respectively. Since 2006 there has been a significant increase in capacity, with the 2013 survey estimating global capacity at 1.5billion seasonal and 6.2billion pandemic doses. Results of the current survey showed that global seasonal influenza vaccine production capacity has decreased since 2013 from 1.504billion doses to 1.467billion doses. However, notwithstanding the overall global decrease in seasonal vaccine capacity there were notable positive changes in the distribution of production capacity with increases noted in South East Asia (SEAR) and the Western Pacific (WPR) regions, albeit on a small scale. Despite a decrease in seasonal capacity, there has been a global increase of pandemic influenza vaccine production capacity from 6.2 billion doses in 2013 to 6.4 billion doses in 2015. This growth can be attributed to a shift towards more quadrivalent vaccine production and also to increased use of adjuvants. Pandemic influenza vaccine production capacity is at its highest recorded levels however challenges remain in maintaining this capacity and in ensuring access in the event of a pandemic to underserved regions. Copyright © 2016. Published by
Sridhar, Saranya; Brokstad, Karl A.; Cox, Rebecca J.
Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people with underlying disease and the elderly, along with occupational groups such a healthcare workers and farm workers. There are two main types of vaccines available: the parenteral inactivated influenza vaccine and the intranasal live attenuated influenza vaccine. The inactivated vaccines are licensed from 6 months of age and have been used for more than 50 years with a good safety profile. Inactivated vaccines are standardized according to the presence of the viral major surface glycoprotein hemagglutinin and protection is mediated by the induction of vaccine strain specific antibody responses. In contrast, the live attenuated vaccines are licensed in Europe for children from 2–17 years of age and provide a multifaceted immune response with local and systemic antibody and T cell responses but with no clear correlate of protection. Here we discuss the immunological immune responses elicited by the two vaccines and discuss future work to better define correlates of protection. PMID:26343192
Ortiz de Lejarazu, Raúl; Tamames, Sonia
Seasonal influenza is an annual challenge for health-care systems, due to factors such as co-circulation of 2 influenza A subtypes jointly with 2 influenza B lineages; the antigenic drift of these virus, which eludes natural immunity, as well as immunity conferred by vaccination; together with influenza impact in terms of morbidity and mortality. Influenza vaccines have been available for more than 70 years and they have progressed in formulation, production and delivery route. Recommendations on vaccination are focused on those with a higher probability of severe disease, and have a progressively wider coverage, and classically based on inactivated vaccines, but with an increasing importance of attenuated live vaccines. More inactivated vaccines are becoming available, from adyuvanted and virosomal vaccines to intradermal delivery, cell-culture or quadrivalent. Overall vaccine effectiveness is about 65%, but varies depending on characteristics of vaccines, virus, population and the outcomes to be prevented, and ranges from less than 10% to almost 90%. Future challenges are formulations that confer more extensive and lasting protection, as well as increased vaccination coverage, especially in groups such as pregnant women and health-care professionals, as well as being extended to paediatrics. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Full Text Available Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people with underlying disease and the elderly, along with occupational groups such a healthcare workers and farm workers. There are two main types of vaccines available: the parenteral inactivated influenza vaccine and the intranasal live attenuated influenza vaccine. The inactivated vaccines are licensed from 6 months of age and have been used for more than 50 years with a good safety profile. Inactivated vaccines are standardized according to the presence of the viral major surface glycoprotein hemagglutinin and protection is mediated by the induction of vaccine strain specific antibody responses. In contrast, the live attenuated vaccines are licensed in Europe for children from 2–17 years of age and provide a multifaceted immune response with local and systemic antibody and T cell responses but with no clear correlate of protection. Here we discuss the immunological immune responses elicited by the two vaccines and discuss future work to better define correlates of protection.
Waterbeemd, van de B.; Streefland, M.; Keulen, van L.J.M.; IJssel, van den J.; Bakker-de Haan, A.M.C.; Eppink, M.H.M.; Pol, van der L.A.
Outer membrane vesicles (OMV) are used as a vaccine against Neisseria meningitidis serogroup B and are traditionally produced with detergent-extraction to remove toxic lipopolysaccharide. Engineered strains with attenuated lipopolysaccharide allowed the use of native vesicles (NOMV) with improved
Hanniffy, S.B.; Carter, A.T.; Hitchin, E.; Wells, J.
Background - Economical and effective vaccines against Streptococcus pneumoniae (pneumococcus) are needed for implementation in poorer countries where the disease burden is highest. Here, we evaluated Lactococcus lactis intracellularly producing the pneumococcal surface protein A (PspA) as a mucosal
García-Basteiro, Alberto L; Alvarez-Pasquín, María-José; Mena, Guillermo; Llupià, Anna; Aldea, Marta; Sequera, Victor-Guillermo; Sanz, Sergi; Tuells, Jose; Navarro-Alonso, José-Antonio; de Arísteguí, Javier; Bayas, José-María
Vacunas.org (http://www.vacunas.org), a website founded by the Spanish Association of Vaccinology offers a personalized service called Ask the Expert, which answers any questions posed by the public or health professionals about vaccines and vaccination. The aim of this study was to analyze the factors associated with questions on vaccination safety and determine the characteristics of questioners and the type of question asked during the period 2008-2010. A total of 1341 questions were finally included in the analysis. Of those, 30% were related to vaccine safety. Questions about pregnant women had 5.01 higher odds of asking about safety (95% CI 2.82-8.93) than people not belonging to any risk group. Older questioners (>50 years) were less likely to ask about vaccine safety compared to younger questioners (OR: 0.44, 95% CI 0.25-0.76). Questions made after vaccination or related to influenza (including H1N1) or travel vaccines were also associated with a higher likelihood of asking about vaccine safety. These results identify risk groups (pregnant women), population groups (older people) and some vaccines (travel and influenza vaccines, including H1N1) where greater efforts to provide improved, more-tailored vaccine information in general and on the Internet are required. Copyright © 2011 Elsevier Ltd. All rights reserved.
Hegerle, N; Dore, G; Guiso, N
Bordetella pertussis is the etiologic agent of whooping cough and has been the target of vaccination for over fifty years. The latest strategies include the use of acellular pertussis vaccines that induce specific immunity against few virulence factors amongst which pertactin is included in three and five component acellular pertussis vaccines. Recently, it has been reported that B. pertussis clinical isolates loose the production of this adhesin in regions reaching high vaccine coverage with vaccines targeting this virulence factor. We here demonstrate that isolates not producing pertactin are capable of sustaining longer infection as compared to pertactin producing isolates in an in vivo model of acellular pertussis immunization. Loosing pertactin production might thus provide a selective advantage to these isolates in this background, which could account for the upraise in prevalence of these pertactin deficient isolates in the population. Copyright © 2014 Elsevier Ltd. All rights reserved.
Poester, Fernando P; Gonçalves, Vítor S P; Paixão, Tatiane A; Santos, Renato L; Olsen, Steven C; Schurig, Gerhardt G; Lage, Andrey P
With the goal of providing an additional tool for controlling bovine brucellosis in Brazil and evaluating the full calf dose in adult cattle, the efficacy of the rough Brucella abortus strain RB51 vaccine was tested in heifers. Thirty-three females of approximately 24 months of age were divided in two groups: one group (n=20) received the RB51 vaccine and the other group (n=13) were used as non-vaccinated control. Animals in the vaccinated group were split in two sub-groups. One sub-group (n=12) was vaccinated subcutaneously with 1.5x10(10) colony forming units (CFU) of RB51 at Day 0 of the experiment and the other sub-group (n=8) was vaccinated subcutaneously with 1.6x10(10) CFU of RB51 at 60 days of gestation (Day 260 of the experiment). All cattle were challenged between 6 and 7 months of pregnancy with 3x10(8) CFU of the virulent strain 2308 of B. abortus by the conjunctival route. Vaccination with RB51 vaccine did not result in the production of any antibodies against the O-side chain of lipopolysaccharide (LPS), as measured by conventional serological tests (rose bengal plate agglutination test (RBPAT), standard tube agglutination test (STAT), and 2-mercaptoethanol test (2ME)). A total of 25% cumulative incidence of abortions was found in the vaccinated group, whereas in the control group the cumulative incidence was 62%. B. abortus RB51 was not isolated from any sample, and no abortions were produced by RB51 vaccination of females at 60 days of pregnancy. The results indicate that vaccination with RB51 prevented 59.4% of abortions, 58.6% of cow infections, and 61.0% of fetal infections. The relative risk (RR) revealed that non-vaccinated animals have 2.462 (95% CI 1.029-5.889) times higher risk of aborting than RB51-vaccinated animals.
Full Text Available An outbreak of influenza H1N1 in 2009, representing the first influenza pandemic of the 21st century, was transmitted to over a million individuals and claimed 18,449 lives. The current status in many countries is to prepare influenza vaccine using cell-based or egg-based killed vaccine. However, traditional influenza vaccine platforms have several limitations. To overcome these limitations, many researchers have tried various approaches to develop alternative production platforms. One of the alternative approach, we reported the efficacy of influenza HA vaccination using a baculoviral DNA vaccine (AcHERV-HA. However, the immune response elicited by the AcHERV-HA vaccine, which only targets the HA antigen, was lower than that of the commercial killed vaccine. To overcome the limitations of this previous vaccine, we constructed a human endogenous retrovirus (HERV envelope-coated, baculovirus-based, virus-like-particle (VLP-forming DNA vaccine (termed AcHERV-VLP against pandemic influenza A/California/04/2009 (pH1N1. BALB/c mice immunized with AcHERV-VLP (1×107 FFU AcHERV-VLP, i.m. and compared with mice immunized with the killed vaccine or mice immunized with AcHERV-HA. As a result, AcHERV-VLP immunization produced a greater humoral immune response and exhibited neutralizing activity with an intrasubgroup H1 strain (PR8, elicited neutralizing antibody production, a high level of interferon-γ secretion in splenocytes, and diminished virus shedding in the lung after challenge with a lethal dose of influenza virus. In conclusion, VLP-forming baculovirus DNA vaccine could be a potential vaccine candidate capable of efficiently delivering DNA to the vaccinee and VLP forming DNA eliciting stronger immunogenicity than egg-based killed vaccines.
Xu, Liming; Zhao, Jingzhuang; Liu, Miao; Kurath, Gael; Ren, Guangming; LaPatra, Scott E.; Yin, Jiasheng; Liu, Hongbai; Feng, Jian; Lu, Tongyan
Infectious hematopoietic necrosis virus (IHNV) is the most important pathogen threatening the aquaculture of salmonid fish in China. In this study, a DNA vaccine, designated pIHNch-G, was constructed with the glycoprotein (G) gene of a Chinese IHNV isolate SD-12 (also called Sn1203) of genotype J. The minimal dose of vaccine required, the expression of the Mx-1 gene in the muscle (vaccine delivery site) and anterior kidney, and the titers of the neutralizing antibodies produced were used to evaluate the vaccine efficacy. To assess the potential utility of the vaccine in controlling IHNV throughout China, the cross protective efficacy of the vaccine was determined by challenging fish with a broad range of IHNV strains from different geographic locations in China. A single 100 ng dose of the vaccine conferred almost full protection to rainbow trout fry (3 g) against waterborne or intraperitoneal injection challenge with IHNV strain SD-12 as early as 4 days post-vaccination (d.p.v.), and significant protection was still observed at 180 d.p.v. Intragenogroup challenges showed that the DNA vaccine provided similar protection to the fish against all the Chinese IHNV isolates tested, suggesting that the vaccine can be widely used in China. Mx-1 gene expression was significantly upregulated in the muscle tissue (vaccine delivery site) and anterior kidney in the vaccinated rainbow trout at both 4 and 7 d.p.v. Similar levels of neutralizing antibodies were determined with each of the Chinese IHNV strains at 60 and 180 d.p.v. This DNA vaccine should play an important role in the control of IHN in China.
Renukaradhya, Gourapura J; Meng, Xiang-Jin; Calvert, Jay G; Roof, Michael; Lager, Kelly M
Within a few years of its emergence in the late 1980s, the PRRS virus had spread globally to become the foremost infectious disease concern for the pork industry. Since 1994, modified live-attenuated vaccines against porcine reproductive and respiratory syndrome virus (PRRSV-MLV) have been widely used, but have failed to provide complete protection against emerging and heterologous field strains of the virus. Moreover, like many other MLVs, PRRSV-MLVs have safety concerns including vertical and horizontal transmission of the vaccine virus and several documented incidences of reversion to virulence. Thus, the development of efficacious inactivated vaccines is warranted for the control and eradication of PRRS. Since the early 1990s, researchers have been attempting to develop inactivated PRRSV vaccines, but most of the candidates have failed to elicit protective immunity even against homologous virus challenge. Recent research findings relating to both inactivated and subunit candidate PRRSV vaccines have shown promise, but they need to be pursued further to improve their heterologous efficacy and cost-effectiveness before considering commercialization. In this comprehensive review, we provide information on attempts to develop PRRSV inactivated and subunit vaccines. These includes various virus inactivation strategies, adjuvants, nanoparticle-based vaccine delivery systems, DNA vaccines, and recombinant subunit vaccines produced using baculovirus, plant, and replication-deficient viruses as vector vaccines. Finally, future directions for the development of innovative non-infectious PRRSV vaccines are suggested. Undoubtedly there remains a need for novel PRRSV vaccine strategies targeted to deliver cross-protective, non-infectious vaccines for the control and eradication of PRRS. Copyright © 2015 Elsevier Ltd. All rights reserved.
Gessner, Bradford D.; Feikin, Daniel R.
Traditionally, vaccines have been evaluated in clinical trials that establish vaccine efficacy (VE) against etiology-confirmed disease outcomes, a measure important for licensure. Yet, VE does not reflect a vaccine’s public health impact because it does not account for relative disease incidence. An additional measure that more directly establishes a vaccine’s public health value is the vaccine preventable disease incidence (VPDI), which is the incidence of disease preventable by vaccine in a given context. We describe how VE and VPDI can vary, sometimes in inverse directions, across disease outcomes and vaccinated populations. We provide examples of how VPDI can be used to reveal the relative public health impact of vaccines in developing countries, which can be masked by focus on VE alone. We recommend that VPDI be incorporated along with VE into the analytic plans of vaccine trials, as well as decisions by funders, ministries of health, and regulatory authorities. PMID:24731817
Fatma Sayed Mohamed
Full Text Available Aim: The present work was established in order to investigate the effect of ultra-corn administration on the immune response of vaccinated calves with FMD bivalent oil vaccine. Material and Methods: Forty calves; at a private farm in EL-Fayoum Governorate (Locality A; were divided into 4 groups where the first group was vaccinated with the locally produced FMD bivalent oil vaccine alone while the 2nd, 3rd and 4th group were vaccinated with the same vaccine simultaneously with the inoculation of 1, 1.5 and 2mL/100kg body weight of ultra-corn respectively to estimate the antibody titer, the suitable dose and effect of ultra-corn as immunostimulant using SNT and ELISA. Also after that used the effective and lowest dose of ultra-corn simultaneously with the vaccine in comparison with the vaccine alone by using 26 calves (Locality B to study the efficacy of ultra-corn simultaneously with vaccine and the vaccine alone via challenge test using the virulent FMDV serotype A,O. Results: Tested serum samples obtained on week intervals post vaccination of all calve groups were subjected for estimation of induced FMD antibodies type A and O using serum neutralization test (SNT and enzyme linked immune sorbent assay (ELISA. Both tests indicate that 1.5mL, 2mL of ultra-corn enhanced the immune response of vaccinated calves exhibiting higher and longer immunity than those received the vaccine alone. In addition 26 calves housed under restrict hygienic measures at Veterinary Serum and Vaccine Research Institute, were divided into 4 groups where group-1 of 10 calves were vaccinated with the bivalent FMD vaccine alone and group-2 was vaccinated with the same vaccine simultaneously with 1.5mL of ultra-corn while group 3 and 4 were kept as control for the challenge test. On the 4th week post vaccination group 1, 2 of these animals was subdivided into 2 subgroups where the challenge test was carried out against type A in a subgroup and O in other subgroup. SNT and
... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bronchitis Vaccine. 113.327 Section... Virus Vaccines § 113.327 Bronchitis Vaccine. Bronchitis Vaccine shall be prepared from virus-bearing... section shall be used for preparing the production seed virus for vaccine production. All serials shall be...
... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Tenosynovitis Vaccine. 113.332 Section... Virus Vaccines § 113.332 Tenosynovitis Vaccine. Tenosynovitis Vaccine shall be prepared from virus... pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials of...
Vaccinated and unvaccinated individuals were compared using univariate and logistic regression analyses to identify factors associated with vaccination status at α ... Various impeding factors such as unavailability of rabies vaccines in the hospital, cost of vaccination, inadequate knowledge about rabies and its vaccination ...
... 42 Public Health 1 2010-10-01 2010-10-01 false Vaccination clinics. 70.9 Section 70.9 Public... INTERSTATE QUARANTINE § 70.9 Vaccination clinics. (a) The Director may establish vaccination clinics, through contract or otherwise, authorized to administer vaccines and/or other prophylaxis. (b) A vaccination fee...
They analized also the mother's preocupation about vaccination. 67.7% of children were vaccinal statue correct. The instruction level and vaccination knowledge of the mothers positively influenced the vaccination statut of children. The mother's occupation are the first raison for no vaccination or incomplete vaccination for ...
Patil, Rajan R
There has been major controversy over vaccine safety in India following newspaper reports citing right to information (RTI) disclosure that there have been increasing vaccine related deaths following immunization in children in the recent years. Secondary data analysis. Adverse effect following immunization (AEFI) events in recent years are being linked to closure of three government owned vaccine producing public sector units (PSU) closures in India. The media reports quoting government sources suggest that the total number of reported deaths due to AEFI in a pre-closure of vaccine PSUs 7 years (2001-2007) was 136, whereas it is 355 in the post vaccine PSU closure 3 years (2008 to 2010). There is an issue of comparability of numbers of AEFI deaths pre- (2001-2007) and post-vaccine PSU closure era (2008-2011) and linking increased AEFI deaths to vaccine PSU closure.
Hecker, Yanina P; Venturini, María C; Campero, Carlos M; Odeón, Anselmo C; Moore, Dadín P
Neosporosis, a disease caused by the obligate intracellular protozoan Neospora caninum, produces abortions in cattle. The severe economic losses in cattle industry justify the need to develop control measures for preventing bovine abortion. Apicomplexan parasitic resistance is associated with T helper 1 immune response mediated by CD4 cytotoxic T lymphocytes, the production of interferon-gamma, interleukin-12, tumor necrosis factor and immunoglobulin G2. The reduction of vertical transmission in subsequent pregnancies and the low levels of abortion repetition suggests the existence of protective immune mechanisms. Inoculation with live tachyzoites before mating protects against infection and abortion. Antecedents of the development of live vaccines against other protozoa stimulate research to develop a live vaccine against N. caninum. On the other hand, an inactivated vaccine with low efficacy against neosporosis is useful in the prevention of abortion in farms with epizootic disease. A neosporosis vaccine should avoid abortion, transplacental transmission and infection persistence. In the present work, advances in vaccine development including lysate of tachyzoites, live parasites, recombinant antigens and vaccine vectors are reviewed.
McGettigan, James P
Rabies remains a global public health threat that kills more than 55,000 people per year. Rabies disproportionately affects children and, therefore, is ranked the seventh most important infectious disease due to years lost. Prevention of human rabies is accomplished by controlling rabies in domestic and wild animals, including the use of vaccination programs. The usefulness of human rabies vaccines is hampered by high cost, complicated vaccination regimens and lack of compliance, especially in areas of Africa and Asia where human rabies infections are endemic. A single-dose vaccine would greatly benefit efforts to combat this global health threat. However, a single-dose vaccine based on current inactivated vaccines does not appear feasible and other approaches are needed. Technology has advanced since modern human rabies vaccines were developed over 40 years ago. In addition, our understanding of immunological principles that influence the outcome of vaccination has increased. This article describes the current status of inactivated rabies virus vaccines and recent developments arising from the use of reverse genetics technologies designed to develop replication-deficient or single-cycle live rabies virus-based vectors for use as a single-dose rabies vaccine for humans. PMID:20923268