Exoproteome and Secretome Derived Broad Spectrum Novel Drug and Vaccine Candidates in Vibrio cholerae Targeted by Piper betel Derived Compounds

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Barh, Debmalya; Barve, Neha; Gupta, Krishnakant; Chandra, Sudha; Jain, Neha; Tiwari, Sandeep; Leon-Sicairos, Nidia; Canizalez-Roman, Adrian; Rodrigues dos Santos, Anderson; Hassan, Syed Shah; Almeida, Síntia; Thiago Jucá Ramos, Rommel; Augusto Carvalho de Abreu, Vinicius; Ribeiro Carneiro, Adriana; de Castro Soares, Siomar; Luiz de Paula Castro, Thiago; Miyoshi, Anderson; Silva, Artur; Kumar, Anil; Narayan Misra, Amarendra; Blum, Kenneth; Braverman, Eric R.; Azevedo, Vasco

2013-01-01

Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC) for most of the pathogenic Vibrio strains. Two targets (uppP and yajC) are novel to Vibrio, and two targets (uppP and ompU) can be used to develop both drugs and vaccines (dual targets) against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species. PMID:23382822

Exoproteome and secretome derived broad spectrum novel drug and vaccine candidates in Vibrio cholerae targeted by Piper betel derived compounds.

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Debmalya Barh

Full Text Available Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC for most of the pathogenic Vibrio strains. Two targets (uppP and yajC are novel to Vibrio, and two targets (uppP and ompU can be used to develop both drugs and vaccines (dual targets against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species.

Targeting of non-dominant antigens as a vaccine strategy to broaden T-cell responses during chronic viral infection

DEFF Research Database (Denmark)

Holst, Peter Johannes; Jensen, Benjamin Anderschou Holbech; Ragonnaud, Emeline

2015-01-01

In this study, we compared adenoviral vaccine vectors with the capacity to induce equally potent immune responses against non-dominant and immunodominant epitopes of murine lymphocytic choriomeningitis virus (LCMV). Our results demonstrate that vaccination targeting non-dominant epitopes facilita......In this study, we compared adenoviral vaccine vectors with the capacity to induce equally potent immune responses against non-dominant and immunodominant epitopes of murine lymphocytic choriomeningitis virus (LCMV). Our results demonstrate that vaccination targeting non-dominant epitopes...... was lost over time in T cells specific for the dominant T cell epitopes, and these cells were fully capable of expanding in response to a new viral challenge. Overall, our data suggests a potential for broadening of the antiviral CD8+ T-cell response by selecting non-dominant antigens to be targeted...

Targeted DNA vaccines for enhanced induction of idiotype-specific B and T cells

International Nuclear Information System (INIS)

Fredriksen, Agnete B.; Sandlie, Inger; Bogen, Bjarne

2012-01-01

Background: Idiotypes (Id) are antigenic determinants localized in variable (V) regions of Ig. Id-specific T and B cells (antibodies) play a role in immunotherapy of Id + tumors. However, vaccine strategies that enhance Id-specific responses are needed. Methods: Id + single-chain fragment variable (scFv) from multiple myelomas and B cell lymphomas were prepared in a fusion format that bivalently target surface molecules on antigen-presenting cells (APC). APC-specific targeting units were either scFv from APC-specific mAb (anti-MHC II, anti-CD40) or chemokines (MIP-1α, RANTES). Homodimeric Id-vaccines were injected intramuscularly or intradermally as plasmids in mice, combined with electroporation. Results: (i) Transfected cells secreted plasmid-encoded Id + fusion proteins to extracellular fluid followed by binding of vaccine molecules to APC. (ii) Targeted vaccine molecules increased Id-specific B and T cell responses. (iii) Bivalency and xenogeneic sequences both contributed to enhanced responses. (iv) Targeted Id DNA vaccines induced tumor resistance against challenges with Id + tumors. (v) Human MIP-1α targeting units enhanced Id-specific responses in mice, due to a cross reaction with murine chemokine receptors. Thus, targeted vaccines designed for humans can be quality tested in mice. (vi) Human Id + scFv from four multiple myeloma patients were inserted into the vaccine format and were successfully tested in mice. (vii) Human MIP-1α vaccine proteins enhanced human T cell responses in vitro. (viii) A hypothetical model for how the APC-targeted vaccine molecules enhance Id-specific T and B cells is presented. Conclusion: Targeted DNA Id-vaccines show promising results in preclinical studies, paving the way for testing in patients.

Targeted DNA vaccines for enhanced induction of idiotype-specific B and T cells

Energy Technology Data Exchange (ETDEWEB)

Fredriksen, Agnete B.; Sandlie, Inger; Bogen, Bjarne, E-mail: bjarne.bogen@medisin.uio.no [Centre for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital, Oslo (Norway)

2012-10-30

Background: Idiotypes (Id) are antigenic determinants localized in variable (V) regions of Ig. Id-specific T and B cells (antibodies) play a role in immunotherapy of Id{sup +} tumors. However, vaccine strategies that enhance Id-specific responses are needed. Methods: Id{sup +} single-chain fragment variable (scFv) from multiple myelomas and B cell lymphomas were prepared in a fusion format that bivalently target surface molecules on antigen-presenting cells (APC). APC-specific targeting units were either scFv from APC-specific mAb (anti-MHC II, anti-CD40) or chemokines (MIP-1α, RANTES). Homodimeric Id-vaccines were injected intramuscularly or intradermally as plasmids in mice, combined with electroporation. Results: (i) Transfected cells secreted plasmid-encoded Id{sup +} fusion proteins to extracellular fluid followed by binding of vaccine molecules to APC. (ii) Targeted vaccine molecules increased Id-specific B and T cell responses. (iii) Bivalency and xenogeneic sequences both contributed to enhanced responses. (iv) Targeted Id DNA vaccines induced tumor resistance against challenges with Id{sup +} tumors. (v) Human MIP-1α targeting units enhanced Id-specific responses in mice, due to a cross reaction with murine chemokine receptors. Thus, targeted vaccines designed for humans can be quality tested in mice. (vi) Human Id{sup +} scFv from four multiple myeloma patients were inserted into the vaccine format and were successfully tested in mice. (vii) Human MIP-1α vaccine proteins enhanced human T cell responses in vitro. (viii) A hypothetical model for how the APC-targeted vaccine molecules enhance Id-specific T and B cells is presented. Conclusion: Targeted DNA Id-vaccines show promising results in preclinical studies, paving the way for testing in patients.

Smallpox vaccines: targets of protective immunity.

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Moss, Bernard

2011-01-01

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.

Evaluation of targeted influenza vaccination strategies via population modeling.

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John Glasser

Full Text Available BACKGROUND: Because they can generate comparable predictions, mathematical models are ideal tools for evaluating alternative drug or vaccine allocation strategies. To remain credible, however, results must be consistent. Authors of a recent assessment of possible influenza vaccination strategies conclude that older children, adolescents, and young adults are the optimal targets, no matter the objective, and argue for vaccinating them. Authors of two earlier studies concluded, respectively, that optimal targets depend on objectives and cautioned against changing policy. Which should we believe? METHODS AND FINDINGS: In matrices whose elements are contacts between persons by age, the main diagonal always predominates, reflecting contacts between contemporaries. Indirect effects (e.g., impacts of vaccinating one group on morbidity or mortality in others result from off-diagonal elements. Mixing matrices based on periods in proximity with others have greater sub- and super-diagonals, reflecting contacts between parents and children, and other off-diagonal elements (reflecting, e.g., age-independent contacts among co-workers, than those based on face-to-face conversations. To assess the impact of targeted vaccination, we used a time-usage study's mixing matrix and allowed vaccine efficacy to vary with age. And we derived mortality rates either by dividing observed deaths attributed to pneumonia and influenza by average annual cases from a demographically-realistic SEIRS model or by multiplying those rates by ratios of (versus adding to them differences between pandemic and pre-pandemic mortalities. CONCLUSIONS: In our simulations, vaccinating older children, adolescents, and young adults averts the most cases, but vaccinating either younger children and older adults or young adults averts the most deaths, depending on the age distribution of mortality. These results are consistent with those of the earlier studies.

Strategies to Improve Vaccine Efficacy against Tuberculosis by Targeting Innate Immunity

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Ulrich E. Schaible

2017-12-01

Full Text Available The global tuberculosis epidemic is the most common cause of death after infectious disease worldwide. Increasing numbers of infections with multi- and extensively drug-resistant variants of the Mycobacterium tuberculosis complex, resistant even to newly discovered and last resort antibiotics, highlight the urgent need for an efficient vaccine. The protective efficacy to pulmonary tuberculosis in adults of the only currently available vaccine, M. bovis BCG, is unsatisfactory and geographically diverse. More importantly, recent clinical studies on new vaccine candidates did not prove to be better than BCG, yet. Here, we propose and discuss novel strategies to improve efficacy of existing anti-tuberculosis vaccines. Modulation of innate immune responses upon vaccination already provided promising results in animal models of tuberculosis. For instance, neutrophils have been shown to influence vaccine efficacy, both, positively and negatively, and stimulate specific antibody secretion. Modulating immune regulatory properties after vaccination such as induction of different types of innate immune cell death, myeloid-derived suppressor or regulatory T cells, production of anti-inflammatory cytokines such as IL-10 may have beneficial effects on protection efficacy. Incorporation of lipid antigens presented via CD1 molecules to T cells have been discussed as a way to enhance vaccine efficacy. Finally, concepts of dendritic cell-based immunotherapies or training the innate immune memory may be exploitable for future vaccination strategies against tuberculosis. In this review, we put a spotlight on host immune networks as potential targets to boost protection by old and new tuberculosis vaccines.

Impact of Targeted Tuberculosis Vaccination Among a Mining Population in South Africa: A Model-Based Study.

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Shrestha, Sourya; Chihota, Violet; White, Richard G; Grant, Alison D; Churchyard, Gavin J; Dowdy, David W

2017-12-15

Optimizing the use of new tools, such as vaccines, may play a crucial role in reaching global targets for tuberculosis (TB) control. Some of the most promising candidate vaccines target adults, although high-coverage mass vaccinations may be logistically more challenging among this population than among children. Vaccine-delivery strategies that target high-risk groups or settings might yield proportionally greater impact than do those that target the general population. We developed an individual-based TB transmission model representing a hypothetical population consisting of people who worked in South African gold mines or lived in associated labor-sending communities. We simulated the implementation of a postinfection adult vaccine with 60% efficacy and a mean effect duration of 10 years. We then compared the impact of a mine-targeted vaccination strategy, in which miners were vaccinated while in the mines, with that of a community-targeted strategy, in which random individuals within the labor-sending communities were vaccinated. Mine-targeted vaccination averted an estimated 0.37 TB cases per vaccine dose compared with 0.25 for community-targeted vaccination, for a relative efficacy of 1.46 (95% range, 1.13-1.91). The added benefit of mine-targeted vaccination primarily reflected the disproportionate demographic burden of TB among the population of adult males as a whole. As novel vaccines for TB are developed, venue-based vaccine delivery that targets high-risk demographic groups may improve both vaccine feasibility and the impact on transmission. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Vaccines targeting drugs of abuse: is the glass half-empty or half-full?

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Janda, Kim D; Treweek, Jennifer B

2011-12-16

The advent of vaccines targeting drugs of abuse heralded a fundamentally different approach to treating substance-related disorders. In contrast to traditional pharmacotherapies for drug abuse, vaccines act by sequestering circulating drugs and terminating the drug-induced 'high' without inducing unwanted neuromodulatory effects. Drug-targeting vaccines have entered clinical evaluation, and although these vaccines show promise from a biomedical viewpoint, the ethical and socioeconomic implications of vaccinating patients against drugs of abuse merit discussion within the scientific community.

Epitope-based peptide vaccine design and target site depiction against Ebola viruses: an immunoinformatics study.

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Khan, M A; Hossain, M U; Rakib-Uz-Zaman, S M; Morshed, M N

2015-07-01

Ebola viruses (EBOVs) have been identified as an emerging threat in recent year as it causes severe haemorrhagic fever in human. Epitope-based vaccine design for EBOVs remains a top priority because a mere progress has been made in this regard. Another reason is the lack of antiviral drug and licensed vaccine although there is a severe outbreak in Central Africa. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites using various immunoinformatics and docking simulation tools. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell was checked for the selected protein. The peptide region spanning 9 amino acids from 42 to 50 and the sequence TLASIGTAF were found as the most potential B and T cell epitopes, respectively. This peptide could interact with 12 HLAs and showed high population coverage up to 80.99%. Using molecular docking, the epitope was further appraised for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post-therapeutic strategy, docking study of predicted 3D structure identified suitable therapeutic inhibitor against targeted protein. However, this computational epitope-based peptide vaccine designing and target site prediction against EBOVs open up a new horizon which may be the prospective way in Ebola viruses research; the results require validation by in vitro and in vivo experiments. © 2015 John Wiley & Sons Ltd.

Integrating epidemiology, psychology, and economics to achieve HPV vaccination targets.

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Basu, Sanjay; Chapman, Gretchen B; Galvani, Alison P

2008-12-02

Human papillomavirus (HPV) vaccines provide an opportunity to reduce the incidence of cervical cancer. Optimization of cervical cancer prevention programs requires anticipation of the degree to which the public will adhere to vaccination recommendations. To compare vaccination levels driven by public perceptions with levels that are optimal for maximizing the community's overall utility, we develop an epidemiological game-theoretic model of HPV vaccination. The model is parameterized with survey data on actual perceptions regarding cervical cancer, genital warts, and HPV vaccination collected from parents of vaccine-eligible children in the United States. The results suggest that perceptions of survey respondents generate vaccination levels far lower than those that maximize overall health-related utility for the population. Vaccination goals may be achieved by addressing concerns about vaccine risk, particularly those related to sexual activity among adolescent vaccine recipients. In addition, cost subsidizations and shifts in federal coverage plans may compensate for perceived and real costs of HPV vaccination to achieve public health vaccination targets.

Unique Safety Issues Associated with Virus Vectored Vaccines: Potential for and Theoretical Consequences of Recombination with Wild Type Virus Strains

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Condit, Richard C.; Williamson, Anna-Lise; Sheets, Rebecca; Seligman, Stephen J.; Monath, Thomas P.; Excler, Jean-Louis; Gurwith, Marc; Bok, Karin; Robertson, James S.; Kim, Denny; Hendry, Michael; Singh, Vidisha; Mac, Lisa M.; Chen, Robert T.

2016-01-01

In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains. PMID:27346303

An innovative influenza vaccination policy: targeting last season's patients.

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Yamin, Dan; Gavious, Arieh; Solnik, Eyal; Davidovitch, Nadav; Balicer, Ran D; Galvani, Alison P; Pliskin, Joseph S

2014-05-01

Influenza vaccination is the primary approach to prevent influenza annually. WHO/CDC recommendations prioritize vaccinations mainly on the basis of age and co-morbidities, but have never considered influenza infection history of individuals for vaccination targeting. We evaluated such influenza vaccination policies through small-world contact networks simulations. Further, to verify our findings we analyzed, independently, large-scale empirical data of influenza diagnosis from the two largest Health Maintenance Organizations in Israel, together covering more than 74% of the Israeli population. These longitudinal individual-level data include about nine million cases of influenza diagnosed over a decade. Through contact network epidemiology simulations, we found that individuals previously infected with influenza have a disproportionate probability of being highly connected within networks and transmitting to others. Therefore, we showed that prioritizing those previously infected for vaccination would be more effective than a random vaccination policy in reducing infection. The effectiveness of such a policy is robust over a range of epidemiological assumptions, including cross-reactivity between influenza strains conferring partial protection as high as 55%. Empirically, our analysis of the medical records confirms that in every age group, case definition for influenza, clinical diagnosis, and year tested, patients infected in the year prior had a substantially higher risk of becoming infected in the subsequent year. Accordingly, considering individual infection history in targeting and promoting influenza vaccination is predicted to be a highly effective supplement to the current policy. Our approach can also be generalized for other infectious disease, computer viruses, or ecological networks.

An innovative influenza vaccination policy: targeting last season's patients.

Directory of Open Access Journals (Sweden)

Dan Yamin

2014-05-01

Full Text Available Influenza vaccination is the primary approach to prevent influenza annually. WHO/CDC recommendations prioritize vaccinations mainly on the basis of age and co-morbidities, but have never considered influenza infection history of individuals for vaccination targeting. We evaluated such influenza vaccination policies through small-world contact networks simulations. Further, to verify our findings we analyzed, independently, large-scale empirical data of influenza diagnosis from the two largest Health Maintenance Organizations in Israel, together covering more than 74% of the Israeli population. These longitudinal individual-level data include about nine million cases of influenza diagnosed over a decade. Through contact network epidemiology simulations, we found that individuals previously infected with influenza have a disproportionate probability of being highly connected within networks and transmitting to others. Therefore, we showed that prioritizing those previously infected for vaccination would be more effective than a random vaccination policy in reducing infection. The effectiveness of such a policy is robust over a range of epidemiological assumptions, including cross-reactivity between influenza strains conferring partial protection as high as 55%. Empirically, our analysis of the medical records confirms that in every age group, case definition for influenza, clinical diagnosis, and year tested, patients infected in the year prior had a substantially higher risk of becoming infected in the subsequent year. Accordingly, considering individual infection history in targeting and promoting influenza vaccination is predicted to be a highly effective supplement to the current policy. Our approach can also be generalized for other infectious disease, computer viruses, or ecological networks.

Putative drug and vaccine target protein identification using comparative genomic analysis of KEGG annotated metabolic pathways of Mycoplasma hyopneumoniae.

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Damte, Dereje; Suh, Joo-Won; Lee, Seung-Jin; Yohannes, Sileshi Belew; Hossain, Md Akil; Park, Seung-Chun

2013-07-01

In the present study, a computational comparative and subtractive genomic/proteomic analysis aimed at the identification of putative therapeutic target and vaccine candidate proteins from Kyoto Encyclopedia of Genes and Genomes (KEGG) annotated metabolic pathways of Mycoplasma hyopneumoniae was performed for drug design and vaccine production pipelines against M.hyopneumoniae. The employed comparative genomic and metabolic pathway analysis with a predefined computational systemic workflow extracted a total of 41 annotated metabolic pathways from KEGG among which five were unique to M. hyopneumoniae. A total of 234 proteins were identified to be involved in these metabolic pathways. Although 125 non homologous and predicted essential proteins were found from the total that could serve as potential drug targets and vaccine candidates, additional prioritizing parameters characterize 21 proteins as vaccine candidate while druggability of each of the identified proteins evaluated by the DrugBank database prioritized 42 proteins suitable for drug targets. Copyright © 2013 Elsevier Inc. All rights reserved.

Intradermal delivery of vaccines: potential benefits and current challenges

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

2011-01-01

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

Hantavirus Gc induces long-term immune protection via LAMP-targeting DNA vaccine strategy.

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Jiang, Dong-Bo; Zhang, Jin-Peng; Cheng, Lin-Feng; Zhang, Guan-Wen; Li, Yun; Li, Zi-Chao; Lu, Zhen-Hua; Zhang, Zi-Xin; Lu, Yu-Chen; Zheng, Lian-He; Zhang, Fang-Lin; Yang, Kun

2018-02-01

due to the advantage afforded by lysosomal targeting after exogenous antigen processing initiation and major histocompatibility complex (MHC) class II antigen presentation trafficking. MHC II-restricted antigen recognition effectively primes HTNV-specific CD4 + T-cells, leading to the promotion of significant immune responses and immunological memory. An epitope-spreading phenomenon was observed, which mirrors the previous result from the Gn study, in which the dominant IFN-γ-responsive hot-spot epitopes were shared between HLA-II and H2 d . Importantly, the pan-epitope reaction to Gc indicated that Gc should be with potential for use in further hantavirus DNA vaccine investigations. Copyright © 2017 Elsevier B.V. All rights reserved.

A longitudinal analysis of the effect of nonmedical exemption law and vaccine uptake on vaccine-targeted disease rates.

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Yang, Y Tony; Debold, Vicky

2014-02-01

We assessed how nonmedical exemption (NME) laws and annual uptake of vaccines required for school or daycare entry affect annual incidence rates for 5 vaccine-targeted diseases: pertussis, measles, mumps, Haemophilus influenzae type B, and hepatitis B. We employed longitudinal mixed-effects models to examine 2001-2008 vaccine-targeted disease data obtained from the National Notifiable Disease Surveillance System. Key explanatory variables were state-level vaccine-specific uptake rates from the National Immunization Survey and a state NME law restrictiveness level. NME law restrictiveness and vaccine uptake were not associated with disease incidence rate for hepatitis B, Haemophilus influenzae type B, measles, or mumps. Pertussis incidence rate, however, was negatively associated with NME law restrictiveness (b = -0.20; P = .03) and diphtheria-pertussis-tetanus vaccine uptake (b = -0.01; P = .05). State NME laws and vaccine uptake rates did not appear to influence lower-incidence diseases but may influence reported disease rates for higher-incidence diseases. If all states increased their NME law restrictiveness by 1 level and diphtheria-pertussis-tetanus uptake by 1%, national annual pertussis cases could decrease by 1.14% (171 cases) and 0.04% (5 cases), respectively.

M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine.

Science.gov (United States)

Ye, Ting; Yue, Yan; Fan, Xiangmei; Dong, Chunsheng; Xu, Wei; Xiong, Sidong

2014-07-31

Efficient delivery of antigen to mucosal associated lymphoid tissue is a first and critical step for successful induction of mucosal immunity by vaccines. Considering its potential transcytotic capability, M cell has become a more and more attractive target for mucosal vaccines. In this research, we designed an M cell-targeting strategy by which mucosal delivery system chitosan (CS) was endowed with M cell-targeting ability via conjugating with a CPE30 peptide, C terminal 30 amino acids of clostridium perfringens enterotoxin (CPE), and then evaluated its immune-enhancing ability in the context of coxsackievirus B3 (CVB3)-specific mucosal vaccine consisting of CS and a plasmid encoding CVB3 predominant antigen VP1. It had shown that similar to CS-pVP1, M cell-targeting CPE30-CS-pVP1 vaccine appeared a uniform spherical shape with about 300 nm diameter and +22 mV zeta potential, and could efficiently protect DNA from DNase I digestion. Mice were orally immunized with 4 doses of CPE30-CS-pVP1 containing 50 μg pVP1 at 2-week intervals and challenged with CVB3 4 weeks after the last immunization. Compared with CS-pVP1 vaccine, CPE30-CS-pVP1 vaccine had no obvious impact on CVB3-specific serum IgG level and splenic T cell immune responses, but significantly increased specific fecal SIgA level and augmented mucosal T cell immune responses. Consequently, much milder myocarditis and lower viral load were witnessed in CPE30-CS-pVP1 immunized group. The enhanced immunogenicity and immunoprotection were associated with the M cell-targeting ability of CPE30-CS-pVP1 which improved its mucosal uptake and transcytosis. Our findings indicated that CPE30-CS-pVP1 may represent a novel prophylactic vaccine against CVB3-induced myocarditis, and this M cell-targeting strategy indeed could be applied as a promising and universal platform for mucosal vaccine development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Vaccine potential of recombinant cathepsin B against Fasciola gigantica.

Science.gov (United States)

Chantree, Pathanin; Phatsara, Manussabhorn; Meemon, Krai; Chaichanasak, Pannigan; Changklungmoa, Narin; Kueakhai, Pornanan; Lorsuwannarat, Natcha; Sangpairoj, Kant; Songkoomkrong, Sineenart; Wanichanon, Chaitip; Itagaki, Tadashi; Sobhon, Prasert

2013-09-01

In Fasciola gigantica, cathepsin Bs, especially cathepsin B2 and B3 are expressed in early juvenile stages, and are proposed to mediate the invasion of host tissues. Thus they are thought to be the target vaccine candidates that can block the invasion and migration of the juvenile parasite. To evaluate their vaccine potential, the recombinant cathepsin B2 (rFgCatB2) and cathepsin B3 (rFgCatB3) were expressed in yeast, Pichia pastoris, and used to immunize mice in combination with Freund's adjuvant to evaluate the protection against the infection by F. gigantica metacercariae, and the induction of immune responses. Mice immunized with both recombinant proteins exhibited high percent of parasite reduction at 60% for rFgCatB2 and 66% for rFgCatB3. Immunization by both antigens induced continuously increasing levels of IgG1 and IgG2a with a higher level of IgG1 isotype, indicating the mixed Th1/Th2 responses with Th2 predominating. When examined individually, the higher levels of IgG1 and IgG2a were correlated with the lower numbers of worm recoveries. Thus, both cathepsin B2 and cathepsin B3 are plausible vaccine candidates whose potential should be further tested in large economic animals. Copyright © 2013 Elsevier Inc. All rights reserved.

Effectiveness of influenza vaccine against laboratory-confirmed influenza, in the late 2011–2012 season in Spain, among population targeted for vaccination

Science.gov (United States)

2013-01-01

Background In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011–2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination. Methods Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed 4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ≥ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval. Conclusions The 2011–2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The suggested decrease in influenza VE with time since vaccination was mostly observed in the elderly population. The decreasing protective effect of the vaccine in the late part of the season could be related to waning vaccine protection because no viral changes were identified throughout the season. PMID:24053661

The specificity of targeted vaccines for APC surface molecules influences the immune response phenotype.

Directory of Open Access Journals (Sweden)

Gunnveig Grødeland

Full Text Available Different diseases require different immune responses for efficient protection. Thus, prophylactic vaccines should prime the immune system for the particular type of response needed for protection against a given infectious agent. We have here tested fusion DNA vaccines which encode proteins that bivalently target influenza hemagglutinins (HA to different surface molecules on antigen presenting cells (APC. We demonstrate that targeting to MHC class II molecules predominantly induced an antibody/Th2 response, whereas targeting to CCR1/3/5 predominantly induced a CD8(+/Th1 T cell response. With respect to antibodies, the polarizing effect was even more pronounced upon intramuscular (i.m delivery as compared to intradermal (i.d. vaccination. Despite these differences in induced immune responses, both vaccines protected against a viral challenge with influenza H1N1. Substitution of HA with ovalbumin (OVA demonstrated that polarization of immune responses, as a consequence of APC targeting specificity, could be extended to other antigens. Taken together, the results demonstrate that vaccination can be tailor-made to induce a particular phenotype of adaptive immune responses by specifically targeting different surface molecules on APCs.

Nanoparticulate STING agonists are potent lymph node-targeted vaccine adjuvants.

Science.gov (United States)

Hanson, Melissa C; Crespo, Monica P; Abraham, Wuhbet; Moynihan, Kelly D; Szeto, Gregory L; Chen, Stephanie H; Melo, Mariane B; Mueller, Stefanie; Irvine, Darrell J

2015-06-01

Cyclic dinucleotides (CDNs) are agonists of stimulator of IFN genes (STING) and have potential as vaccine adjuvants. However, cyclic di-GMP (cdGMP) injected s.c. shows minimal uptake into lymphatics/draining lymph nodes (dLNs) and instead is rapidly distributed to the bloodstream, leading to systemic inflammation. Here, we encapsulated cdGMP within PEGylated lipid nanoparticles (NP-cdGMP) to redirect this adjuvant to dLNs. Compared with unformulated CDNs, encapsulation blocked systemic dissemination and markedly enhanced dLN accumulation in murine models. Delivery of NP-cdGMP increased CD8+ T cell responses primed by peptide vaccines and enhanced therapeutic antitumor immunity. A combination of a poorly immunogenic liposomal HIV gp41 peptide antigen and NP-cdGMP robustly induced type I IFN in dLNs, induced a greater expansion of vaccine-specific CD4+ T cells, and greatly increased germinal center B cell differentiation in dLNs compared with a combination of liposomal HIV gp41 and soluble CDN. Further, NP-cdGMP promoted durable antibody titers that were substantially higher than those promoted by the well-studied TLR agonist monophosphoryl lipid A and comparable to a much larger dose of unformulated cdGMP, without the systemic toxicity of the latter. These results demonstrate that nanoparticulate delivery safely targets CDNs to the dLNs and enhances the efficacy of this adjuvant. Moreover, this approach can be broadly applied to other small-molecule immunomodulators of interest for vaccines and immunotherapy.

PML-RARA-targeted DNA vaccine induces protective immunity in a mouse model of leukemia.

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Padua, Rose Ann; Larghero, Jerome; Robin, Marie; le Pogam, Carol; Schlageter, Marie-Helene; Muszlak, Sacha; Fric, Jan; West, Robert; Rousselot, Philippe; Phan, Thi Hai; Mudde, Liesbeth; Teisserenc, Helene; Carpentier, Antoine F; Kogan, Scott; Degos, Laurent; Pla, Marika; Bishop, J Michael; Stevenson, Freda; Charron, Dominique; Chomienne, Christine

2003-11-01

Despite improved molecular characterization of malignancies and development of targeted therapies, acute leukemia is not curable and few patients survive more than 10 years after diagnosis. Recently, combinations of different therapeutic strategies (based on mechanisms of apoptosis, differentiation and cytotoxicity) have significantly increased survival. To further improve outcome, we studied the potential efficacy of boosting the patient's immune response using specific immunotherapy. In an animal model of acute promyelocytic leukemia, we developed a DNA-based vaccine by fusing the human promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARA) oncogene to tetanus fragment C (FrC) sequences. We show for the first time that a DNA vaccine specifically targeted to an oncoprotein can have a pronounced effect on survival, both alone and when combined with all-trans retinoic acid (ATRA). The survival advantage is concomitant with time-dependent antibody production and an increase in interferon-gamma (IFN-gamma). We also show that ATRA therapy on its own triggers an immune response in this model. When DNA vaccination and conventional ATRA therapy are combined, they induce protective immune responses against leukemia progression in mice and may provide a new approach to improve clinical outcome in human leukemia.

RhoC a new target for therapeutic vaccination against metastatic cancer

DEFF Research Database (Denmark)

Wenandy, L.; Sorensen, R.B.; Straten, P.T.

2008-01-01

Most cancer deaths are due to the development of metastases. Increased expression of RhoC is linked to enhanced metastatic potential in multiple cancers. Consequently, the RhoC protein is an attractive target for drug design. The clinical application of immunotherapy against cancer is rapidly...... of cancer makes RhoC a very attractive target for anti-cancer immunotherapy. Herein, we describe an HLA-A3 restricted epitope from RhoC, which is recognized by cytotoxic T cells. Moreover, RhoC-specific T cells show cytotoxic potential against HLA-matched cancer cells of different origin. Thus, RhoC may...... moving forward in multiple areas, including the adoptive transfer of anti-tumor-reactive T cells and the use of "therapeutic" vaccines. The over-expression of RhoC in cancer and the fact that immune escape by down regulation or loss of expression of this protein would reduce the morbidity and mortality...

Of monkeys and men: immunomic profiling of sera from humans and non-human primates resistant to schistosomiasis reveals novel potential vaccine candidates.

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Pearson, Mark S; Becker, Luke; Driguez, Patrick; Young, Neil D; Gaze, Soraya; Mendes, Tiago; Li, Xiao-Hong; Doolan, Denise L; Midzi, Nicholas; Mduluza, Takafira; McManus, Donald P; Wilson, R Alan; Bethony, Jeffrey M; Nausch, Norman; Mutapi, Francisca; Felgner, Philip L; Loukas, Alex

2015-01-01

Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR) to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80), tetraspanins, glutathione-S-transferases, and glucose transporters (SGTP1), as well as previously uncharacterized proteins. Reactive IgG1 responses were not elevated in exposed individuals who did not acquire DIR. To complement our human subjects study, we screened for antigen targets of rhesus macaques rendered resistant to S. japonicum by experimental infection followed by self-cure, and discovered a number of new and known vaccine targets, including major targets recognized by our human subjects. This study has further validated the immunomics-based approach to schistosomiasis vaccine antigen discovery and identified numerous novel potential vaccine antigens.

Of monkeys and men: immunomic profiling of sera from humans and non-human primates resistant to schistosomiasis reveals novel potential vaccine candidates

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Mark ePearson

2015-05-01

Full Text Available Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80, tetraspanins, glutathione-S-transferases and glucose transporters (SGTP1, as well as previously uncharacterized proteins. Reactive IgG1 responses were not elevated in exposed individuals who did not acquire DIR. To complement our human subjects study, we screened for antigen targets of rhesus macaques rendered resistant to Schistosoma japonicum by experimental infection followed by self-cure, and discovered a number of new and known vaccine targets, including major targets recognised by our human subjects. This study has further validated the immunomics-based approach to schistosomiasis vaccine antigen discovery and identified numerous novel potential vaccine antigens.

Schools as potential vaccination venue for vaccines outside regular EPI schedule: results from a school census in Pakistan.

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Soofi, Sajid Bashir; Haq, Inam-Ul; Khan, M Imran; Siddiqui, Muhammad Bilal; Mirani, Mushtaq; Tahir, Rehman; Hussain, Imtiaz; Puri, Mahesh K; Suhag, Zamir Hussain; Khowaja, Asif R; Lasi, Abdul Razzaq; Clemens, John D; Favorov, Michael; Ochiai, R Leon; Bhutta, Zulfiqar A

2012-01-06

in developing countries including Pakistan. Many schools in the targeted townships participated in immunization activities but they were not carried out regularly. In the wake of low immunization coverage in Pakistan, schools can be used as a potential venue not only for non-EPI vaccines, but for a catch up vaccination of routine vaccines.

Schools as potential vaccination venue for vaccines outside regular EPI schedule: results from a school census in Pakistan

Directory of Open Access Journals (Sweden)

Soofi Sajid

2012-01-01

education programs are not part of the regular school curriculum in developing countries including Pakistan. Many schools in the targeted townships participated in immunization activities but they were not carried out regularly. In the wake of low immunization coverage in Pakistan, schools can be used as a potential venue not only for non-EPI vaccines, but for a catch up vaccination of routine vaccines.

Neighborhood-targeted and case-triggered use of a single dose of oral cholera vaccine in an urban setting: Feasibility and vaccine coverage.

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Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Muller, Vincent; Llosa, Augusto E; Uzzeni, Florent; Luquero, Francisco J; Ciglenecki, Iza; Azman, Andrew S

2017-06-01

In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area. Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign ('case-triggered' interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0-73.7) and was highest among children ages 5-14 years (90.0%, 95% CI 85.7-94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68-0.96). In the case-triggered interventions, each lasting 1-2 days, coverage varied (range: 30-87%) with an average of 51.0% (95% CI 41.7-60.3). Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.

Hatchery Vaccination Against Poultry Viral Diseases: Potential Mechanisms and Limitations.

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Abdul-Cader, Mohamed Sarjoon; Palomino-Tapia, Victor; Amarasinghe, Aruna; Ahmed-Hassan, Hanaa; De Silva Senapathi, Upasama; Abdul-Careem, Mohamed Faizal

Commercial broiler and layer chickens are heavily vaccinated against economically important viral diseases with a view of preventing morbidity, mortality, and production impacts encountered during short production cycles. Hatchery vaccination is performed through in ovo embryo vaccination prehatch or spray and subcutaneous vaccinations performed at the day of hatch before the day-old chickens are being placed in barns with potentially contaminated environments. Commercially, multiple vaccines (e.g., live, live attenuated, and viral vectored vaccines) are available to administer through these routes within a short period (embryo day 18 prehatch to day 1 posthatch). Although the ability to mount immune response, especially the adaptive immune response, is not optimal around the hatch, it is possible that the efficacy of these vaccines depends partly on innate host responses elicited in response to replicating vaccine viruses. This review focuses on the current knowledge of hatchery vaccination in poultry and potential mechanisms of hatchery vaccine-mediated protective responses and limitations.

Identification of Novel Potential Vaccine Candidates against Tuberculosis Based on Reverse Vaccinology

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Gloria P. Monterrubio-López

2015-01-01

Full Text Available Tuberculosis (TB is a chronic infectious disease, considered as the second leading cause of death worldwide, caused by Mycobacterium tuberculosis. The limited efficacy of the bacillus Calmette-Guérin (BCG vaccine against pulmonary TB and the emergence of multidrug-resistant TB warrants the need for more efficacious vaccines. Reverse vaccinology uses the entire proteome of a pathogen to select the best vaccine antigens by in silico approaches. M. tuberculosis H37Rv proteome was analyzed with NERVE (New Enhanced Reverse Vaccinology Environment prediction software to identify potential vaccine targets; these 331 proteins were further analyzed with VaxiJen for the determination of their antigenicity value. Only candidates with values ≥0.5 of antigenicity and 50% of adhesin probability and without homology with human proteins or transmembrane regions were selected, resulting in 73 antigens. These proteins were grouped by families in seven groups and analyzed by amino acid sequence alignments, selecting 16 representative proteins. For each candidate, a search of the literature and protein analysis with different bioinformatics tools, as well as a simulation of the immune response, was conducted. Finally, we selected six novel vaccine candidates, EsxL, PE26, PPE65, PE_PGRS49, PBP1, and Erp, from M. tuberculosis that can be used to improve or design new TB vaccines.

Development of Antibody-Based Vaccines Targeting the Tumor Vasculature.

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Zhuang, Xiaodong; Bicknell, Roy

2016-01-01

A functional vasculature is essential for tumor progression and malignant cell metastasis. Endothelial cells lining blood vessels in the tumor are exposed to a unique microenvironment, which in turn induces expression of specific proteins designated as tumor endothelial markers (TEMs). TEMs either localized at the plasma membrane or secreted into the extracellular matrix are accessible for antibody targeting, which can be either infused or generated de novo via vaccination. Recent studies have demonstrated vaccines against several TEMs can induce a strong antibody response accompanied by a potent antitumor effect in animal models. These findings present an exciting field for novel anticancer therapy development. As most of the TEMs are self-antigens, breaking tolerance is necessary for a successful vaccine. This chapter describes approaches to efficiently induce a robust antibody response against the tumor vasculature.

Optimizing targeted vaccination across cyber-physical networks: an empirically based mathematical simulation study.

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Mones, Enys; Stopczynski, Arkadiusz; Pentland, Alex 'Sandy'; Hupert, Nathaniel; Lehmann, Sune

2018-01-01

Targeted vaccination, whether to minimize the forward transmission of infectious diseases or their clinical impact, is one of the 'holy grails' of modern infectious disease outbreak response, yet it is difficult to achieve in practice due to the challenge of identifying optimal targets in real time. If interruption of disease transmission is the goal, targeting requires knowledge of underlying person-to-person contact networks. Digital communication networks may reflect not only virtual but also physical interactions that could result in disease transmission, but the precise overlap between these cyber and physical networks has never been empirically explored in real-life settings. Here, we study the digital communication activity of more than 500 individuals along with their person-to-person contacts at a 5-min temporal resolution. We then simulate different disease transmission scenarios on the person-to-person physical contact network to determine whether cyber communication networks can be harnessed to advance the goal of targeted vaccination for a disease spreading on the network of physical proximity. We show that individuals selected on the basis of their closeness centrality within cyber networks (what we call 'cyber-directed vaccination') can enhance vaccination campaigns against diseases with short-range (but not full-range) modes of transmission. © 2018 The Author(s).

Potential impact of reactive vaccination in controlling cholera ...

African Journals Online (AJOL)

Background. To contain ongoing cholera outbreaks, the World Health Organization has suggested that reactive vaccination should be considered in addition to its previous control measures. Objectives. To explore the potential impact of a hypothetical reactive oral cholera vaccination using the example of the recent ...

Seasonal influenza vaccination coverage rate of target groups in selected cities and provinces in China by season (2009/10 to 2011/12.

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Lei Zhou

Full Text Available BACKGROUND: The objectives of the survey were to identify the level of influenza vaccination coverage in China in three influenza seasons 2009/10 to 2011/12, and to find out potential predictors for seasonal influenza vaccination. METHODS: In September and October 2011, representative urban household telephone surveys were conducted in five provinces in China with a response rate of 6%. Four target groups were defined for analysis: 1 children ≤ 5 years old; 2 elderly persons aged ≥ 60 years old; 3 health care workers (persons working in the medical field and 4 chronically ill persons. RESULTS: The overall mean vaccination rate was 9.0%. Among the four target groups, the rate of vaccination of children aged ≤ 5 years old (mean = 26% was highest and the rate of elderly people aged ≥ 60 years old (mean = 7.4% was the lowest, while the rates of persons who suffer from a chronic illness (mean = 9.4% and health care workers (9.5% were similar. A subsidy for influenza vaccination, age group, health care workers, suffering from a chronic illness and living in Eastern China were independent significant predictors for influenza vaccination. CONCLUSIONS: The seasonal influenza vaccination coverage rates among urban populations in selected cities and provinces in China were far below previously reported rates in developed countries. Influenza vaccination coverage rates differed widely between different target groups and provinces in China. Subsidy policy might have a positive effect on influenza vaccination rate, but further cost-effectiveness studies, as well as the vaccination rate associated factors studies are still needed to inform strategies to increase coverage.

Laser vaccine adjuvants. History, progress, and potential.

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

2014-01-01

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

Vector-transmitted disease vaccines: targeting salivary proteins in transmission (SPIT).

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McDowell, Mary Ann

2015-08-01

More than half the population of the world is at risk for morbidity and mortality from vector-transmitted diseases, and emerging vector-transmitted infections are threatening new populations. Rising insecticide resistance and lack of efficacious vaccines highlight the need for novel control measures. One such approach is targeting the vector-host interface by incorporating vector salivary proteins in anti-pathogen vaccines. Debate remains about whether vector saliva exposure exacerbates or protects against more severe clinical manifestations, induces immunity through natural exposure or extends to all vector species and associated pathogens. Nevertheless, exploiting this unique biology holds promise as a viable strategy for the development of vaccines against vector-transmitted diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human neonatal rotavirus vaccine (RV3-BB) targets rotavirus from birth

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Thobari, Jarir At; Satria, Cahya Dewi; Handley, Amanda; Watts, Emma; Cowley, Daniel; Nirwati, Hera; Ackland, James; Standish, Jane; Justice, Frances; Byars, Gabrielle; Lee, Katherine J.; Barnes, Graeme L.; Bachtiar, Novilia S.; Icanervilia, Ajeng Viska; Boniface, Karen; Bogdanovic-Sakran, Nada; Pavlic, Daniel; Bishop, Ruth F.; Kirkwood, Carl D.; Buttery, Jim P.; Soenarto, Yati

2018-01-01

Background A birth dose strategy using a neonatal rotavirus vaccine to target early prevention of rotavirus disease may address remaining barriers to global vaccine implementation. Methods We conducted a randomized, placebo-controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) to prevent rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB administered in a neonatal schedule at 0-5 days, 8 and 14 weeks or infant schedule at 8, 14 and 18 weeks, or placebo. Laboratory-confirmed rotavirus gastroenteritis was graded using a modified Vesikari score. The primary analysis was efficacy against severe rotavirus gastroenteritis from two weeks after all doses to 18 months in the combined vaccine group (neonatal and infant schedule) compared with placebo. Results Vaccine efficacy against severe rotavirus gastroenteritis to 18 months was 63% in the combined vaccine group (95% CI 34, 80; p<0.001), 75% in the neonatal vaccine group (95% confidence interval [CI] 44, 91; p<0.001) and 51% in the infant vaccine group (95% CI 7, 76; p=0.03) in the per protocol analysis, with similar results in the intention-to-treat analysis. Vaccine efficacy to 12 months was 94% in the neonatal vaccine group (95%CI 56, 99; p=0.006). Vaccine take occurred in 78/83 (94%) in the neonatal vaccine group and 83/84 (99%) in the infant vaccine group. The vaccine was well tolerated, with similar incidence of adverse events in vaccine and placebo recipients. Conclusion RV3-BB was efficacious, immunogenic and well-tolerated when administered in a neonatal or infant schedule in Indonesia. PMID:29466164

How influenza vaccination policy may affect vaccine logistics.

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Assi, Tina-Marie; Rookkapan, Korngamon; Rajgopal, Jayant; Sornsrivichai, Vorasith; Brown, Shawn T; Welling, Joel S; Norman, Bryan A; Connor, Diana L; Chen, Sheng-I; Slayton, Rachel B; Laosiritaworn, Yongjua; Wateska, Angela R; Wisniewski, Stephen R; Lee, Bruce Y

2012-06-22

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.

Potential for rabies control through dog vaccination in wildlife-abundant communities of Tanzania.

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Fitzpatrick, Meagan C; Hampson, Katie; Cleaveland, Sarah; Meyers, Lauren Ancel; Townsend, Jeffrey P; Galvani, Alison P

2012-01-01

Canine vaccination has been successful in controlling rabies in diverse settings worldwide. However, concerns remain that coverage levels which have previously been sufficient might be insufficient in systems where transmission occurs both between and within populations of domestic dogs and other carnivores. To evaluate the effectiveness of vaccination targeted at domestic dogs when wildlife also contributes to transmission, we applied a next-generation matrix model based on contract tracing data from the Ngorongoro and Serengeti Districts in northwest Tanzania. We calculated corresponding values of R(0), and determined, for policy purposes, the probabilities that various annual vaccination targets would control the disease, taking into account the empirical uncertainty in our field data. We found that transition rate estimates and corresponding probabilities of vaccination-based control indicate that rabies transmission in this region is driven by transmission within domestic dogs. Different patterns of rabies transmission between the two districts exist, with wildlife playing a more important part in Ngorongoro and leading to higher recommended coverage levels in that district. Nonetheless, our findings indicate that an annual dog vaccination campaign achieving the WHO-recommended target of 70% will control rabies in both districts with a high level of certainty. Our results support the feasibility of controlling rabies in Tanzania through dog vaccination.

Potential for rabies control through dog vaccination in wildlife-abundant communities of Tanzania.

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Meagan C Fitzpatrick

Full Text Available Canine vaccination has been successful in controlling rabies in diverse settings worldwide. However, concerns remain that coverage levels which have previously been sufficient might be insufficient in systems where transmission occurs both between and within populations of domestic dogs and other carnivores. To evaluate the effectiveness of vaccination targeted at domestic dogs when wildlife also contributes to transmission, we applied a next-generation matrix model based on contract tracing data from the Ngorongoro and Serengeti Districts in northwest Tanzania. We calculated corresponding values of R(0, and determined, for policy purposes, the probabilities that various annual vaccination targets would control the disease, taking into account the empirical uncertainty in our field data. We found that transition rate estimates and corresponding probabilities of vaccination-based control indicate that rabies transmission in this region is driven by transmission within domestic dogs. Different patterns of rabies transmission between the two districts exist, with wildlife playing a more important part in Ngorongoro and leading to higher recommended coverage levels in that district. Nonetheless, our findings indicate that an annual dog vaccination campaign achieving the WHO-recommended target of 70% will control rabies in both districts with a high level of certainty. Our results support the feasibility of controlling rabies in Tanzania through dog vaccination.

Potential Target Antigens for a Universal Vaccine in Epithelial Ovarian Cancer

NARCIS (Netherlands)

Vermeij, R.; Daemen, T.; de Bock, G.H.; de Graeff, P.; Leffers, N.; Lambeck, A.; Ten Hoor, K.A.; Hollema, H.; van der Zee, A.G.J.; Nijman, H.W.

2010-01-01

The prognosis of epithelial ovarian cancer (EOC), the primary cause of death from gynaecological malignancies, has only modestly improved over the last decades. Immunotherapeutic treatment using a cocktail of antigens has been proposed as a "universal" vaccine strategy. We determined the expression

Analysis of the evidence on the efficacy and safety of CYD-TDV dengue vaccine and its potential licensing and implementation through Mexico´s Universal Vaccination Program

Directory of Open Access Journals (Sweden)

Mauricio Hernández-Ávila

2016-01-01

questions that should be answered to properly assess the safety profile of the product and the target populations of potential benefit. In this regard we consider it would be informative to complete the 6-year follow-up after starting vaccination, according to the company’s own study protocol recommended by the World Health Organization. As with any new vaccine, the potential licensing and implementation of the CYD-TDV as part of Mexico’s vaccination program, requires a clear definition of the balance between the expected benefits and risks. Particularly with a vaccine with variable efficacy and some signs of risk, in the probable case of licensing, the post-licensed period must involve the development of detailed protocols to immediately identify risks or any health event associated with vaccination.

Pricing of new vaccines

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McGlone, Sarah M

2010-01-01

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

Pricing of new vaccines.

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Lee, Bruce Y; McGlone, Sarah M

2010-08-01

New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical, and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following 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.

Pricing of new vaccines

OpenAIRE

Lee, Bruce Y; McGlone, Sarah M

2010-01-01

New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following eleven components: (1) Conduct a target population analysis; (2) Map potential competitors and alternatives; (3) Construct a vaccine targe...

The potential economic value of a cutaneous leishmaniasis vaccine in seven endemic countries in the Americas.

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Bacon, Kristina M; Hotez, Peter J; Kruchten, Stephanie D; Kamhawi, Shaden; Bottazzi, Maria Elena; Valenzuela, Jesus G; Lee, Bruce Y

2013-01-07

Cutaneous leishmaniasis (CL) and its associated complications, including mucocutaneous leishmaniasis (MCL) and diffuse CL (DCL) have emerged as important neglected tropical diseases in Latin America, especially in areas associated with human migration, conflict, and recent deforestation. Because of the limitations of current chemotherapeutic approaches to CL, MCL, and DCL, several prototype vaccines are in different states of product and clinical development. We constructed and utilized a Markov decision analytic computer model to evaluate the potential economic value of a preventative CL vaccine in seven countries in Latin America: Bolivia, Brazil, Colombia, Ecuador, Mexico, Peru, and Venezuela. The results indicated that even a vaccine with a relatively short duration of protection and modest efficacy could be recommended for use in targeted locations, as it could prevent a substantial number of cases at low-cost and potentially even result in cost savings. If the population in the seven countries were vaccinated using a vaccine that provides at least 10 years of protection, an estimated 41,000-144,784 CL cases could be averted, each at a cost less than the cost of current recommended treatments. Further, even a vaccine providing as little as five years duration of protection with as little as 50% efficacy remains cost-effective compared with chemotherapy; additional scenarios resembling epidemic settings such as the one that occurred in Chaparral, Colombia in 2004 demonstrate important economic benefits. Copyright © 2012 Elsevier Ltd. All rights reserved.

A computational method for identification of vaccine targets from protein regions of conserved human leukocyte antigen binding

DEFF Research Database (Denmark)

Olsen, Lars Rønn; Simon, Christian; Kudahl, Ulrich J.

2015-01-01

Background: Computational methods for T cell-based vaccine target discovery focus on selection of highly conserved peptides identified across pathogen variants, followed by prediction of their binding of human leukocyte antigen molecules. However, experimental studies have shown that T cells often...... target diverse regions in highly variable viral pathogens and this diversity may need to be addressed through redefinition of suitable peptide targets. Methods: We have developed a method for antigen assessment and target selection for polyvalent vaccines, with which we identified immune epitopes from...... variable regions, where all variants bind HLA. These regions, although variable, can thus be considered stable in terms of HLA binding and represent valuable vaccine targets. Results: We applied this method to predict CD8+ T-cell targets in influenza A H7N9 hemagglutinin and significantly increased...

Understanding human papillomavirus vaccination intentions: comparative utility of the theory of reasoned action and the theory of planned behavior in vaccine target age women and men.

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Fisher, William A; Kohut, Taylor; Salisbury, Claire M A; Salvadori, Marina I

2013-10-01

Human papillomavirus (HPV) is an exceedingly prevalent sexually transmitted infection with serious medical, sexual, and relationship consequences. HPV vaccine protection is available but vaccine uptake is very inconsistent. This research applies two major theories of health behavior uptake, the Theory of Reasoned Action and the Theory of Planned Behavior, in an effort to understand intentions to receive HPV vaccine among vaccine target age women and men. The Theory of Reasoned Action asserts that attitudes toward HPV vaccination and perceptions of social support for HPV vaccination are the determinants of intentions to be vaccinated, whereas the Theory of Planned Behavior holds that attitudes toward vaccination, perceptions of social support for vaccination, and perceived ability to get vaccinated are the determinants of intentions to be vaccinated. Canadian university men (N=118) and women (N=146) in the HPV vaccine target age range took part in this correlational study online. Participants completed standard measures of attitudes toward HPV vaccination, perceptions of social support for vaccination, perceived ability to get vaccinated, beliefs about vaccination, and intentions to be vaccinated in the coming semester. Findings confirmed the propositions of the Theory of Reasoned Action and indicated that attitudes toward undergoing HPV vaccination and perceptions of social support for undergoing HPV vaccination contributed uniquely to the prediction of women's (R2=0.53) and men's (R2=0.44) intentions to be vaccinated in the coming semester. Clinical and public health education should focus on strengthening attitudes and perceptions of social support for HPV vaccination, and on the basic beliefs that appear to underlie attitudes and perceptions of social support for HPV vaccination, in efforts to promote HPV vaccine uptake. © 2013 International Society for Sexual Medicine.

Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization

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Zhang, Han [Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582 (Japan); Sonoda, Koh-Hei, E-mail: sonodak@med.kyushu-u.ac.jp [Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582 (Japan); Hijioka, Kuniaki; Qiao, Hong; Oshima, Yuji; Ishibashi, Tatsuro [Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582 (Japan)

2009-04-17

Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8{sup +} T cells reduced pathological preretinal NV, with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8{sup +} T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.

Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization

International Nuclear Information System (INIS)

Zhang, Han; Sonoda, Koh-Hei; Hijioka, Kuniaki; Qiao, Hong; Oshima, Yuji; Ishibashi, Tatsuro

2009-01-01

Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8 + T cells reduced pathological preretinal NV, with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8 + T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.

Targeted outreach hepatitis B vaccination program in high-risk adults : The fundamental challenge of the last mile

NARCIS (Netherlands)

Mangen, M. J.J.; Stibbe, H; Urbanus, A.; Siedenburg, E C; Waldhober, Q; de Wit, G. A.; Steenbergen, Eric J

2017-01-01

Background The aim of this study was to evaluate the cost-effectiveness of the on-going decentralised targeted hepatitis B vaccination program for behavioural high-risk groups operated by regional public health services in the Netherlands since 1-November-2002. Target groups for free vaccination are

Vaccine potential of recombinant saposin-like protein 2 against Fasciolosis gigantica in mice.

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Kueakhai, Pornanan; Changklungmoa, Narin; Riengrojpitak, Suda; Chaichanasak, Pannigan; Meemon, Krai; Chaithirayanon, Kulathida; Chantree, Pathanin; Sansri, Veerawat; Itagaki, Tadashi; Sobhon, Prasert

2013-11-12

Saposin-like protein 2 (SAP-2) is a protein that adult of Fasciola spp. use to lyse plasma membrane of red blood cells, so that their contents can be digested by proteases for the parasites' nutrients. Thus SAP-2 is a plausible target for vaccination against these parasites. Recombinant Fasciola gigantica saposin-like protein 2 (rFgSAP-2) was expressed in Escherichia coli BL21 (DE3). A vaccination was performed in ICR mice (n=10) by subcutaneous injection with 50μg of rFgSAP-2 combined with Freund's adjuvant. At 2 weeks after the second boost, mice were infected with 30 F. gigantica metacercariae by oral route. The percentages of protection of rFgSAP-2 vaccine against F. gigantica were estimated to be 76.4-78.5% when compared with non vaccinated-infected and adjuvant-infected controls, respectively. The antibodies in immune sera of vaccinated mice were shown by immuno-blotting to react with native FgSAP-2 in the extract of 2- and 4-week-old juvenile parasites. By determining the levels of IgG1 and IgG2a in the immune sera, which are indicative of Th2 and Th1 immune responses, it was found that both Th1 and Th2 humoral immune response were significantly increased in rFgSAP-2 immunized group compared with the control groups, with higher levels of Th2 (IgG1) than Th1 (IgG2a). The levels of serum aspartate aminotransferase (AST) and alanine transaminase (ALT) in rFgSAP-2-immunized group showed no significant difference from those of the non-immunized and infected group, indicating that early juvenile parasites induced liver parenchyma damage, even though the numbers of worm recoveries were significantly different. This study indicates that rFgSAP-2 has a high potential as a vaccine candidate against F. gigantica in mice, and this potential will be tested in larger economic animals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Immunogenicity of DNA vaccines encoding simian immunodeficiency virus antigen targeted to dendritic cells in rhesus macaques.

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Matthias Tenbusch

Full Text Available BACKGROUND: Targeting antigens encoded by DNA vaccines to dendritic cells (DCs in the presence of adjuvants enhances their immunogenicity and efficacy in mice. METHODOLOGY/PRINCIPAL FINDINGS: To explore the immunogenicity of this approach in non-human primates, we generated a single chain antibody to the antigen uptake receptor DEC-205 expressed on rhesus macaque DCs. DNA vaccines encoding this single chain antibody fused to the SIV capsid protein were delivered to six monkeys each by either intramuscular electroporation or conventional intramuscular injection co-injected or not with poly ICLC, a stabilized poly I: C analogue, as adjuvant. Antibodies to capsid were induced by the DC-targeting and non-targeting control DNA delivered by electroporation while conventional DNA immunization at a 10-fold higher dose of DNA failed to induce detectable humoral immune responses. Substantial cellular immune responses were also observed after DNA electroporation of both DNAs, but stronger responses were induced by the non-targeting vaccine. Conventional immunization with the DC-targeting DNA at a 10-fold higher dose did not give rise to substantial cellular immune responses, neither when co-injected with poly ICLC. CONCLUSIONS/SIGNIFICANCE: The study confirms the potent immunogenicity of DNA vaccines delivered by electroporation. Targeting the DNA via a single chain antibody to DEC-205 expressed by DCs, however, does not improve the immunogenicity of the antigens in non-human primates.

Biochemical Characterization and Vaccine Potential of a Heme-Binding Glutathione Transferase from the Adult Hookworm Ancylostoma caninum

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Zhan, Bin; Liu, Sen; Perally, Samirah; Xue, Jian; Fujiwara, Ricardo; Brophy, Peter; Xiao, Shuhua; Liu, Yueyuan; Feng, Jianjun; Williamson, Angela; Wang, Yan; Bueno, Lilian L.; Mendez, Susana; Goud, Gaddam; Bethony, Jeffrey M.; Hawdon, John M.; Loukas, Alex; Jones, Karen; Hotez, Peter J.

2005-01-01

We report the cloning and expression of Ac-GST-1, a novel glutathione S-transferase from the adult hookworm Ancylostoma caninum, and its possible role in parasite blood feeding and as a vaccine target. The predicted Ac-GST-1 open reading frame contains 207 amino acids (mass, 24 kDa) and exhibited up to 65% amino acid identity with other nematode GSTs. mRNA encoding Ac-GST-1 was detected in adults, eggs, and larval stages, but the protein was detected only in adult hookworm somatic extracts and excretory/secretory products. Using antiserum to the recombinant protein, Ac-GST-1 was immunolocalized to the parasite hypodermis and muscle tissue and weakly to the intestine. Recombinant Ac-GST-1 was enzymatically active, as determined by conjugation of glutathione to a model substrate, and exhibited a novel high-affinity binding site for hematin. The possible role of Ac-GST-1 in parasite heme detoxification during hemoglobin digestion or heme uptake prompted interest in evaluating it as a potential vaccine antigen. Vaccination of dogs with Ac-GST-1 resulted in a 39.4% reduction in the mean worm burden and 32.3% reduction in egg counts compared to control dogs following larval challenge, although the reductions were not statistically significant. However, hamsters vaccinated with Ac-GST-1 exhibited statistically significant worm reduction (53.7%) following challenge with heterologous Necator americanus larvae. These studies suggest that Ac-GST-1 is a possible drug and vaccine target for hookworm infection. PMID:16177370

A mass vaccination campaign targeting adults and children to prevent typhoid fever in Hechi; Expanding the use of Vi polysaccharide vaccine in Southeast China: A cluster-randomized trial

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Yang Hong-hui

2005-05-01

Full Text Available Abstract Background One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS and group A meningococcal PS vaccines in southern China. Methods The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported. Results The campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged ≤ 15 years (90% than in adolescents and young adults (70%. Planned mop-up activities increased the coverage by 17%. The overall vaccine wastage was 11%. The cold chain was maintained and documented. 66 individuals reported of adverse events out of all vaccinees, where fever (21%, malaise (19% and local redness (19% were the major symptoms; no life-threatening event occurred. Three needle-sharp events were reported. Conclusion The mass immunization proved feasible and safe, and vaccine coverage was high. Emphasis should be placed on: injection safety measures, community involvement and incorporation of mop-up strategies into any vaccination campaign. School-based and all-age Vi mass immunizations programs are potentially important public health strategies for prevention of typhoid fever in high-risk populations in southern China.

Vaccine potential of Nipah virus-like particles.

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Pramila Walpita

2011-04-01

Full Text Available Nipah virus (NiV was first recognized in 1998 in a zoonotic disease outbreak associated with highly lethal febrile encephalitis in humans and a predominantly respiratory disease in pigs. Periodic deadly outbreaks, documentation of person-to-person transmission, and the potential of this virus as an agent of agroterror reinforce the need for effective means of therapy and prevention. In this report, we describe the vaccine potential of NiV virus-like particles (NiV VLPs composed of three NiV proteins G, F and M. Co-expression of these proteins under optimized conditions resulted in quantifiable amounts of VLPs with many virus-like/vaccine desirable properties including some not previously described for VLPs of any paramyxovirus: The particles were fusogenic, inducing syncytia formation; PCR array analysis showed NiV VLP-induced activation of innate immune defense pathways; the surface structure of NiV VLPs imaged by cryoelectron microscopy was dense, ordered, and repetitive, and consistent with similarly derived structure of paramyxovirus measles virus. The VLPs were composed of all the three viral proteins as designed, and their intracellular processing also appeared similar to NiV virions. The size, morphology and surface composition of the VLPs were consistent with the parental virus, and importantly, they retained their antigenic potential. Finally, these particles, formulated without adjuvant, were able to induce neutralizing antibody response in Balb/c mice. These findings indicate vaccine potential of these particles and will be the basis for undertaking future protective efficacy studies in animal models of NiV disease.

R&D in Vaccines Targeting Neglected Diseases: An Exploratory Case Study Considering Funding for Preventive Tuberculosis Vaccine Development from 2007 to 2014.

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Costa Barbosa Bessa, Theolis; Santos de Aragão, Erika; Medeiros Guimarães, Jane Mary; de Araújo Almeida, Bethânia

2017-01-01

Based on an exploratory case study regarding the types of institutions funding the research and development to obtain new tuberculosis vaccines, this article intends to provoke discussion regarding the provision of new vaccines targeting neglected disease. Although our findings and discussion are mainly relevant to the case presented here, some aspects are more generally applicable, especially regarding the dynamics of development in vaccines to prevent neglected diseases. Taking into account the dynamics of innovation currently seen at work in the vaccine sector, a highly concentrated market dominated by few multinational pharmaceutical companies, we feel that global PDP models can play an important role throughout the vaccine development cycle. In addition, the authors call attention to issues surrounding the coordination of actors and resources in the research, development, manufacturing, and distribution processes of vaccine products arising from PDP involvement.

Future of human Chlamydia vaccine: potential of self-adjuvanting biodegradable nanoparticles as safe vaccine delivery vehicles.

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Sahu, Rajnish; Verma, Richa; Dixit, Saurabh; Igietseme, Joseph U; Black, Carolyn M; Duncan, Skyla; Singh, Shree R; Dennis, Vida A

2018-03-01

There is a persisting global burden and considerable public health challenge by the plethora of ocular, genital and respiratory diseases caused by members of the Gram-negative bacteria of the genus Chlamydia. The major diseases are conjunctivitis and blinding trachoma, non-gonococcal urethritis, cervicitis, pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, and interstitial pneumonia. The failures in screening and other prevention programs led to the current medical opinion that an efficacious prophylactic vaccine is the best approach to protect humans from chlamydial infections. Unfortunately, there is no human Chlamydia vaccine despite successful veterinary vaccines. A major challenge has been the effective delivery of vaccine antigens to induce safe and effective immune effectors to confer long-term protective immunity. The dawn of the era of biodegradable polymeric nanoparticles and the adjuvanted derivatives may accelerate the realization of the dream of human vaccine in the foreseeable future. Areas covered: This review focuses on the current status of human chlamydial vaccine research, specifically the potential of biodegradable polymeric nanovaccines to provide efficacious Chlamydia vaccines in the near future. Expert commentary: The safety of biodegradable polymeric nanoparticles-based experimental vaccines with or without adjuvants and the array of available chlamydial vaccine candidates would suggest that clinical trials in humans may be imminent. Also, the promising results from vaccine testing in animal models could lead to human vaccines against trachoma and reproductive diseases simultaneously.

Potential of Cationic Liposomes as Adjuvants/Delivery Systems for Tuberculosis Subunit Vaccines.

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Khademi, Farzad; Taheri, Ramezan Ali; Momtazi-Borojeni, Amir Abbas; Farnoosh, Gholamreza; Johnston, Thomas P; Sahebkar, Amirhossein

2018-04-27

The weakness of the BCG vaccine and its highly variable protective efficacy in controlling tuberculosis (TB) in different age groups as well as in different geographic areas has led to intense efforts towards the development and design of novel vaccines. Currently, there are several strategies to develop novel TB vaccines. Each strategy has its advantages and disadvantages. However, the most important of these strategies is the development of subunit vaccines. In recent years, the use of cationic liposome-based vaccines has been considered due to their capacity to elicit strong humoral and cellular immune responses against TB infections. In this review, we aim to evaluate the potential for cationic liposomes to be used as adjuvants/delivery systems for eliciting immune responses against TB subunit vaccines. The present review shows that cationic liposomes have extensive applications either as adjuvants or delivery systems, to promote immune responses against Mycobacterium tuberculosis (Mtb) subunit vaccines. To overcome several limitations of these particles, they were used in combination with other immunostimulatory factors such as TDB, MPL, TDM, and Poly I:C. Cationic liposomes can provide long-term storage of subunit TB vaccines at the injection site, confer strong electrostatic interactions with APCs, potentiate both humoral and cellular (CD4 and CD8) immune responses, and induce a strong memory response by the immune system. Therefore, cationic liposomes can increase the potential of different TB subunit vaccines by serving as adjuvants/delivery systems. These properties suggest the use of cationic liposomes to produce an efficient vaccine against TB infections.

Nonspecific effects of neonatal and infant vaccination

DEFF Research Database (Denmark)

Aaby, Peter; Kollmann, Tobias R; Benn, Christine Stabell

2014-01-01

Vaccines can have nonspecific effects through their modulation of responses to infections not specifically targeted by the vaccine. However, lack of knowledge about the underlying immunological mechanisms and molecular cause-and-effect relationships prevent use of this potentially powerful early-...

Malaria vaccines and their potential role in the elimination of malaria

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Greenwood Brian M

2008-12-01

Full Text Available Abstract Research on malaria vaccines is currently directed primarily towards the development of vaccines that prevent clinical malaria. Malaria elimination, now being considered seriously in some epidemiological situations, requires a different vaccine strategy, since success will depend on killing all parasites in the community in order to stop transmission completely. The feature of the life-cycles of human malarias that presents the greatest challenge to an elimination programme is the persistence of parasites as asymptomatic infections. These are an important source from which transmission to mosquitoes can occur. Consequently, an elimination strategy requires a community-based approach covering all individuals and not just those who are susceptible to clinical malaria. The progress that has been made in development of candidate malaria vaccines is reviewed. It is unlikely that many of these will have the efficacy required for complete elimination of parasites, though they may have an important role to play as part of future integrated control programmes. Vaccines for elimination must have a high level of efficacy in order to stop transmission to mosquitoes. This might be achieved with some pre-erythrocytic stage candidate vaccines or by targeting the sexual stages directly with transmission-blocking vaccines. An expanded malaria vaccine programme with such objectives is now a priority.

Comparative genomics study for the identification of drug and vaccine targets in Staphylococcus aureus: MurA ligase enzyme as a proposed candidate.

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Ghosh, Soma; Prava, Jyoti; Samal, Himanshu Bhusan; Suar, Mrutyunjay; Mahapatra, Rajani Kanta

2014-06-01

Now-a-days increasing emergence of antibiotic-resistant pathogenic microorganisms is one of the biggest challenges for management of disease. In the present study comparative genomics, metabolic pathways analysis and additional parameters were defined for the identification of 94 non-homologous essential proteins in Staphylococcus aureus genome. Further study prioritized 19 proteins as vaccine candidates where as druggability study reports 34 proteins suitable as drug targets. Enzymes from peptidoglycan biosynthesis, folate biosynthesis were identified as candidates for drug development. Furthermore, bacterial secretory proteins and few hypothetical proteins identified in our analysis fulfill the criteria of vaccine candidates. As a case study, we built a homology model of one of the potential drug target, MurA ligase, using MODELLER (9v12) software. The model has been further selected for in silico docking study with inhibitors from the DrugBank database. Results from this study could facilitate selection of proteins for entry into drug design and vaccine production pipelines. Copyright © 2014 Elsevier B.V. All rights reserved.

Pharmacists as providers: targeting pneumococcal vaccinations to high risk populations.

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Taitel, Michael; Cohen, Ed; Duncan, Ian; Pegus, Cheryl

2011-10-19

Older adults and persons with chronic conditions are at increased risk for pneumococcal disease. Severe pneumococcal disease represents a substantial humanistic and economic burden to society. Although pneumococcal vaccination (PPSV) can decrease risk for serious consequences, vaccination rates are suboptimal. As more people seek annual influenza vaccinations at community pharmacies, pharmacists have the ability to identify at-risk patients and provide PPSV. The objective of this study was to evaluate the impact of pharmacists educating at-risk patients on the importance of receiving a pneumococcal vaccination. Using de-identified claims from a large, national pharmacy chain, all patients who had received an influenza vaccination between August 1, 2010 and November 14, 2010 and who were eligible for PPSV were identified for the analysis. Based on the Advisory Committee on Immunization Practices recommendations, at-risk patients were identified as over 65 years of age or as aged 2-64 with a comorbid conditions. A benchmark medical and pharmacy claims database of commercial and Medicare health plan members was used to derive a PPSV vaccination rate typical of traditional care delivery to compare to pharmacy-based vaccination. Period incidence of PPSV was calculated and compared. Among the 1.3 million at-risk patients who were vaccinated by a pharmacist during the study period, 65,598 (4.88%) also received a pneumococcal vaccine. This vaccination rate was significantly higher than the benchmark rate of 2.90% (34,917/1,204,104; pvaccination rate (6.60%; 26,430/400,454) of any age group. Pharmacists were successful at identifying at-risk patients and providing additional immunization services. Concurrent immunization of PPSV with influenza vaccination by pharmacists has potential to improve PPSV coverage. These results support the expanding role of community pharmacists in the provision of wellness and prevention services. Copyright © 2011 Elsevier Ltd. All rights

Polyvalent Vaccines Targeting Oncogenic Driver Pathways

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Mary L. (Nora) Disis, MD, is the Athena Distinguished Professor of Breast Cancer Research and Associate Dean for Translational Health Sciences in the University of Washington (UW) School of Medicine. She is a Professor of Medicine and Adjunct Professor of Pathology and Obstetrics and Gynecology at UW, and a Member of the Fred Hutchinson Cancer Research Center (FHCRC). She is also an American Cancer Society Clinical Professor and a Komen Scholar. In addition to directing work in the Tumor Vaccine Group, Dr. Disis is the Director of the Institute of Translational Health Sciences and the Director for the Center for Translational Medicine in Women’s Health at the UW. Dr. Disis is an expert in breast and ovarian cancer immunology and translational research. She is one of the pioneering investigators who discovered that HER-2/neu is a tumor antigen. Her work has led to several clinical trials which evaluate boosting immunity to HER-2/neu with cancer vaccines. Her research interest is in the discovery of new molecular immunologic targets in solid tumors for the development of vaccine and cellular therapy for the treatment and prevention of common malignancies. Dr. Disis is a member of Alpha Omega Alpha and the American Society of Clinical Investigation. She is also the Editor-in-Chief for JAMA Oncology, and is a member of several committees and task forces for both the American Society of Clinical Oncology (ASCO) and the American Association for Cancer Research (AACR). Dr. Disis received her MD from the University of Nebraska Medical School and completed a residency and chief residency in Internal Medicine at the University of Illinois in Chicago and her fellowship in oncology at UW/FHCRC.

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

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Carlos Wong

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

Methods and Protocols for Developing Prion Vaccines.

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Marciniuk, Kristen; Taschuk, Ryan; Napper, Scott

2016-01-01

Prion diseases denote a distinct form of infectivity that is based in the misfolding of a self-protein (PrP(C)) into a pathological, infectious conformation (PrP(Sc)). Efforts to develop vaccines for prion diseases have been complicated by the potential dangers that are associated with induction of immune responses against a self-protein. As a consequence, there is considerable appeal for vaccines that specifically target the misfolded prion conformation. Such conformation-specific immunotherapy is made possible through the identification of vaccine targets (epitopes) that are exclusively presented as a consequence of misfolding. An immune response directed against these targets, termed disease-specific epitopes (DSEs), has the potential to spare the function of the native form of the protein while clearing, or neutralizing, the infectious isomer. Although identification of DSEs represents a critical first step in the induction of conformation-specific immune responses, substantial efforts are required to translate these targets into functional vaccines. Due to the poor immunogenicity that is inherent to self-proteins, and that is often associated with short peptides, substantial efforts are required to overcome tolerance-to-self and maximize the resultant immune response following DSE-based immunization. This often includes optimization of target sequences in terms of immunogenicity and development of effective formulation and delivery strategies for the associated peptides. Further, these vaccines must satisfy additional criteria from perspectives of specificity (PrP(C) vs. PrP(Sc)) and safety (antibody-induced template-driven misfolding of PrP(C)). The emphasis of this report is on the steps required to translate DSEs into prion vaccines and subsequent evaluation of the resulting immune responses.

A potential disruptive technology in vaccine development: gene-based vaccines and their application to infectious diseases.

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Kaslow, David C

2004-10-01

Vaccine development requires an amalgamation of disparate disciplines and has unique economic and regulatory drivers. Non-viral gene-based delivery systems, such as formulated plasmid DNA, are new and potentially disruptive technologies capable of providing 'cheaper, simpler, and more convenient-to-use' vaccines. Typically and somewhat ironically, disruptive technologies have poorer product performance, at least in the near-term, compared with the existing conventional technologies. Because successful product development requires that the product's performance must meet or exceed the efficacy threshold for a desired application, the appropriate selection of the initial product applications for a disruptive technology is critical for its successful evolution. In this regard, the near-term successes of gene-based vaccines will likely be for protection against bacterial toxins and acute viral and bacterial infections. Recent breakthroughs, however, herald increasing rather than languishing performance improvements in the efficacy of gene-based vaccines. Whether gene-based vaccines ultimately succeed in eliciting protective immunity in humans to persistent intracellular pathogens, such as HIV, malaria and tuberculosis, for which the conventional vaccine technologies have failed, remains to be determined. A success against any one of the persistent intracellular pathogens would be sufficient proof that gene-based vaccines represent a disruptive technology against which future vaccine technologies will be measured.

Potential Impact of Accelerating the Primary Dose of Rotavirus Vaccine in Infants

OpenAIRE

Halvorson, Elizabeth E.; Peters, Timothy R.; Snively, Beverly M.; Poehling, Katherine A.

2012-01-01

We estimated the potential impact of administering the first dose of rotavirus vaccine at 6 weeks (42 days of life) instead of 2 months of age, which is permissible for all U.S. vaccines recommended at 2 months of age, on rotavirus hospitalization rates. We used published data for hospitalization rates, vaccine coverage, and vaccine efficacy after one dose and assumed a two-week delay in seroconversion after vaccine administration in the United States. Administering the first dose of rotaviru...

Endoplasmic reticulum targeting sequence enhances HBV-specific cytotoxic T lymphocytes induced by a CTL epitope-based DNA vaccine

International Nuclear Information System (INIS)

Xu Wei; Chu Yiwei; Zhang Ruihua; Xu Huanbin; Wang Ying; Xiong Sidong

2005-01-01

CD8 + T cells play a critical role in protective immunity against Hepatitis B Virus (HBV). Epitope-based DNA vaccines expressing HBV-dominant CTL epitopes can be used as candidate vaccines capable of inducing cytotoxic T Lymphocytes (CTL) responses. A plasmid DNA encoding a CTL epitope of HBV core antigen, HBc 18-27 , was constructed. Intramuscular immunization of C57BL/6 mice with this DNA vaccine resulted in successful induction of HBV-specific CTL responses. In order to promote transportation of the peptide into endoplasmic reticulum (ER) to bind to MHC class I molecules for optimal class I antigen presentation, an ER targeting sequence (ERTS) was fused with the C 18-27 encoding gene. ERTS fusion significantly enhanced specific CD8 + T cell responses in terms of CTL cytolysis as well as IFN-γ secretion. This enhancement was correlated with promoted epitope presentation on target cell surface. We report here an enhanced immunogenicity of an epitope-based DNA vaccine using an ER targeting signal sequence, which has significant implications for future design of therapeutic HBV vaccine

Recombinant vaccines and the development of new vaccine strategies

Energy Technology Data Exchange (ETDEWEB)

Nascimento, I.P.; Leite, L.C.C. [Centro de Biotecnologia, Instituto Butantan, São Paulo, SP (Brazil)

2012-09-07

Vaccines were initially developed on an empirical basis, relying mostly on attenuation or inactivation of pathogens. Advances in immunology, molecular biology, biochemistry, genomics, and proteomics have added new perspectives to the vaccinology field. The use of recombinant proteins allows the targeting of immune responses focused against few protective antigens. There are a variety of expression systems with different advantages, allowing the production of large quantities of proteins depending on the required characteristics. Live recombinant bacteria or viral vectors effectively stimulate the immune system as in natural infections and have intrinsic adjuvant properties. DNA vaccines, which consist of non-replicating plasmids, can induce strong long-term cellular immune responses. Prime-boost strategies combine different antigen delivery systems to broaden the immune response. In general, all of these strategies have shown advantages and disadvantages, and their use will depend on the knowledge of the mechanisms of infection of the target pathogen and of the immune response required for protection. In this review, we discuss some of the major breakthroughs that have been achieved using recombinant vaccine technologies, as well as new approaches and strategies for vaccine development, including potential shortcomings and risks.

Recombinant vaccines and the development of new vaccine strategies

Directory of Open Access Journals (Sweden)

I.P. Nascimento

2012-12-01

Full Text Available Vaccines were initially developed on an empirical basis, relying mostly on attenuation or inactivation of pathogens. Advances in immunology, molecular biology, biochemistry, genomics, and proteomics have added new perspectives to the vaccinology field. The use of recombinant proteins allows the targeting of immune responses focused against few protective antigens. There are a variety of expression systems with different advantages, allowing the production of large quantities of proteins depending on the required characteristics. Live recombinant bacteria or viral vectors effectively stimulate the immune system as in natural infections and have intrinsic adjuvant properties. DNA vaccines, which consist of non-replicating plasmids, can induce strong long-term cellular immune responses. Prime-boost strategies combine different antigen delivery systems to broaden the immune response. In general, all of these strategies have shown advantages and disadvantages, and their use will depend on the knowledge of the mechanisms of infection of the target pathogen and of the immune response required for protection. In this review, we discuss some of the major breakthroughs that have been achieved using recombinant vaccine technologies, as well as new approaches and strategies for vaccine development, including potential shortcomings and risks.

Recombinant vaccines and the development of new vaccine strategies

International Nuclear Information System (INIS)

Nascimento, I.P.; Leite, L.C.C.

2012-01-01

Vaccines were initially developed on an empirical basis, relying mostly on attenuation or inactivation of pathogens. Advances in immunology, molecular biology, biochemistry, genomics, and proteomics have added new perspectives to the vaccinology field. The use of recombinant proteins allows the targeting of immune responses focused against few protective antigens. There are a variety of expression systems with different advantages, allowing the production of large quantities of proteins depending on the required characteristics. Live recombinant bacteria or viral vectors effectively stimulate the immune system as in natural infections and have intrinsic adjuvant properties. DNA vaccines, which consist of non-replicating plasmids, can induce strong long-term cellular immune responses. Prime-boost strategies combine different antigen delivery systems to broaden the immune response. In general, all of these strategies have shown advantages and disadvantages, and their use will depend on the knowledge of the mechanisms of infection of the target pathogen and of the immune response required for protection. In this review, we discuss some of the major breakthroughs that have been achieved using recombinant vaccine technologies, as well as new approaches and strategies for vaccine development, including potential shortcomings and risks

HPV vaccines: a controversial issue?

Science.gov (United States)

Nicol, A F; Andrade, C V; Russomano, F B; Rodrigues, L L S; Oliveira, N S; Provance, D W

2016-01-01

Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

HPV vaccines: a controversial issue?

Directory of Open Access Journals (Sweden)

A.F. Nicol

2016-01-01

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.

Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth.

Science.gov (United States)

Bines, Julie E; At Thobari, Jarir; Satria, Cahya Dewi; Handley, Amanda; Watts, Emma; Cowley, Daniel; Nirwati, Hera; Ackland, James; Standish, Jane; Justice, Frances; Byars, Gabrielle; Lee, Katherine J; Barnes, Graeme L; Bachtiar, Novilia S; Viska Icanervilia, Ajeng; Boniface, Karen; Bogdanovic-Sakran, Nada; Pavlic, Daniel; Bishop, Ruth F; Kirkwood, Carl D; Buttery, Jim P; Soenarto, Yati

2018-02-22

A strategy of administering a neonatal rotavirus vaccine at birth to target early prevention of rotavirus gastroenteritis may address some of the barriers to global implementation of a rotavirus vaccine. We conducted a randomized, double-blind, placebo-controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) in preventing rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB, administered according to a neonatal schedule (0 to 5 days, 8 weeks, and 14 weeks of age) or an infant schedule (8 weeks, 14 weeks, and 18 weeks of age), or placebo. The primary analysis was conducted in the per-protocol population, which included only participants who received all four doses of vaccine or placebo within the visit windows, with secondary analyses performed in the intention-to-treat population, which included all participants who underwent randomization. Among the 1513 participants in the per-protocol population, severe rotavirus gastroenteritis occurred up to the age of 18 months in 5.6% of the participants in the placebo group (28 of 504 babies), in 1.4% in the neonatal-schedule vaccine group (7 of 498), and in 2.7% in the infant-schedule vaccine group (14 of 511). This resulted in a vaccine efficacy of 75% (95% confidence interval [CI], 44 to 91) in the neonatal-schedule group (PBill and Melinda Gates Foundation and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612001282875 .).

The effectiveness of measles-mumps-rubella (MMR) vaccination in the prevention of pediatric hospitalizations for targeted and untargeted infections: A retrospective cohort study.

Science.gov (United States)

La Torre, Giuseppe; Saulle, Rosella; Unim, Brigid; Meggiolaro, Angela; Barbato, Angelo; Mannocci, Alice; Spadea, Antonietta

2017-08-03

To evaluate the effectiveness of the measles-mumps-rubella (MMR) vaccine in reducing hospitalizations for infectious disease, targeted and not targeted, as well as from respiratory diseases in children in Rome. The cohort was recomposed through record linkage of 2 archives (vaccination register and hospital discharge records. The analysis included 11,004 children. 20.9% did not receive the MMR vaccination, 49% and 30.1% received one and 2 doses. There were no hospitalizations for rubella, 2 for mumps, and 12 for measles. The vaccine was highly protective against measles and mumps hospitalizations (HR = 0.10; 95% CI: 0.03.0.34). Regarding all infectious diseases there were 414 hospitalizations, and the vaccine was protective (HR = 0.29; 95% CI: 0.25 to 0.34). Concerning respiratory diseases, there were 809 admissions (7.4%), and the vaccine was highly protective (HR: 0.18; 95% CI: 0.07 to 0.48). MMR vaccination is effective for the primary prevention of target and not targeted infectious diseases and may also limit hospitalizations for respiratory diseases.

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

Science.gov (United States)

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

2017-10-25

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

Potential safety issues and other factors that may affect the introduction and uptake of rotavirus vaccines

Science.gov (United States)

Aliabadi, N.; Tate, J.E.; Parashar, U.D.

2018-01-01

Rotavirus vaccines have demonstrated significant impact in reducing the burden of morbidity and mortality from childhood diarrhoea in countries that have implemented routine vaccination to date. Despite this success, in many countries, rotavirus vaccine coverage remains lower than that of other routine childhood vaccines. Several issues may potentially affect vaccine uptake, namely safety concerns related to intussusception with consequent age restrictions on rotavirus vaccination, contamination with porcine circovirus, vaccine-derived reassortant strains and hospitalization in newborn nurseries at time of administration of live oral rotavirus vaccine. In addition to these safety concerns, other factors may also affect uptake, including lower vaccine efficacy in the developing world, potential emergence of strains escaping from vaccine protection resulting in lower overall impact of a vaccination programme and sustainable vaccine financing. Although further work is needed to address some of these concerns, global policy bodies have reaffirmed that the benefits of rotavirus vaccination outweigh the risks, and vaccine use is recommended globally. PMID:27129416

Potential safety issues and other factors that may affect the introduction and uptake of rotavirus vaccines.

Science.gov (United States)

Aliabadi, N; Tate, J E; Parashar, U D

2016-12-01

Rotavirus vaccines have demonstrated significant impact in reducing the burden of morbidity and mortality from childhood diarrhoea in countries that have implemented routine vaccination to date. Despite this success, in many countries, rotavirus vaccine coverage remains lower than that of other routine childhood vaccines. Several issues may potentially affect vaccine uptake, namely safety concerns related to intussusception with consequent age restrictions on rotavirus vaccination, contamination with porcine circovirus, vaccine-derived reassortant strains and hospitalization in newborn nurseries at time of administration of live oral rotavirus vaccine. In addition to these safety concerns, other factors may also affect uptake, including lower vaccine efficacy in the developing world, potential emergence of strains escaping from vaccine protection resulting in lower overall impact of a vaccination programme and sustainable vaccine financing. Although further work is needed to address some of these concerns, global policy bodies have reaffirmed that the benefits of rotavirus vaccination outweigh the risks, and vaccine use is recommended globally. Published by Elsevier Ltd.

Green revolution vaccines, edible vaccines | Tripurani | African ...

African Journals Online (AJOL)

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 ...

Protective potential of antioxidant enzymes as vaccines for schistosomiasis in a non-human primate model

Directory of Open Access Journals (Sweden)

Claudia eCarvalho-Queiroz

2015-06-01

Full Text Available Schistosomiasis remains a major cause of morbidity in the world. The challenge today is not so much in the clinical management of individual patients, but rather in population-based control of transmission in endemic areas. Recent large-scale efforts aimed at limiting schistosomiasis have produced limited success. There is an urgent need for complementary approaches, such as vaccines. We demonstrated previously that anti-oxidant enzymes such as Cu-Zn superoxide dismutase (SOD and glutathione S peroxidase (GPX, when administered as DNA-based vaccines induced significant levels of protection in inbred mice, greater than the target 40% reduction in worm burden compared to controls set as a minimum by the WHO. These results led us to investigate if immunization of non-human primates with antioxidants would stimulate an immune response that could confer protection, as a prelude for human trials. Issues of vaccine toxicity and safety that were difficult to address in mice were also investigated. All baboons in the study were examined clinically throughout the study and no adverse reactions occurred to the immunization. When our outbred baboons were vaccinated with two different formulations of SOD (SmCT-SOD and SmEC-SOD or one of GPX (SmGPX, they showed a reduction in worm number to varying degrees, when compared with the control group. More pronounced, vaccinated animals showed decreased bloody diarrhea, days of diarrhea and egg excretion (transmission, as well as reduction of eggs in the liver tissue and in the large intestine (pathology compared to controls. Specific IgG antibodies were present in sera after immunizations and 10 weeks after challenge infection compared to controls. PBMC, mesenteric and inguinal node cells from vaccinated animals proliferated and produced high levels of cytokines and chemokines in response to crude and recombinant antigens compared with controls. These data demonstrate the potential of antioxidants as vaccine

Sex differences in the vaccine-specific and non-targeted effects of vaccines

DEFF Research Database (Denmark)

Flanagan, Katie L; Klein, Sabra L; Skakkebaek, Niels E

2011-01-01

to eliminate infectious diseases through vaccination programmes, the relative impact of NSE of vaccines on mortality is likely to increase, raising important questions regarding the future of certain vaccine schedules. A diverse group of scientists met in Copenhagen to discuss non-specific and sex...

Targeted Facebook Advertising is a Novel and Effective Method of Recruiting Participants into a Human Papillomavirus Vaccine Effectiveness Study.

Science.gov (United States)

Subasinghe, Asvini K; Nguyen, Margaret; Wark, John D; Tabrizi, Sepehr N; Garland, Suzanne M

2016-07-22

Targeted advertising using social networking sites (SNS) as a recruitment strategy in health research is in its infancy. The aim of this study was to determine the feasibility of targeted Facebook advertisements to increase recruitment of unvaccinated women into a human papillomavirus (HPV) vaccine effectiveness study. Between September 2011 and November 2013, females aged 18 to 25 years, residing in Victoria, Australia, were recruited through Facebook advertisements relating to general women's health. From November 2013 to June 2015, targeted advertising campaigns were implemented to specifically recruit women who had not received the HPV vaccine. Consenting participants were invited to complete an online questionnaire and those who had ever had sexual intercourse were asked to provide a self-collected vaginal swab. The HPV vaccination status of participants was confirmed from the National HPV Vaccination Program Register (NHVPR). The campaign comprised 10 advertisements shown between September 2011 and June 2015 which generated 55,381,637 impressions, yielding 23,714 clicks, at an overall cost of AUD $22,078.85. A total of 919 participants were recruited. A greater proportion of unvaccinated women (50.4%, 131/260) were recruited into the study following targeted advertising, compared with those recruited (19.3%, 127/659) prior to showing the modified advertisement (Padvertising is a rapid and cost-effective way of recruiting young unvaccinated women into a HPV vaccine effectiveness study.

An approximation of herd effect due to vaccinating children against seasonal influenza - a potential solution to the incorporation of indirect effects into static models.

Science.gov (United States)

Van Vlaenderen, Ilse; Van Bellinghen, Laure-Anne; Meier, Genevieve; Nautrup, Barbara Poulsen

2013-01-22

Indirect herd effect from vaccination of children offers potential for improving the effectiveness of influenza prevention in the remaining unvaccinated population. Static models used in cost-effectiveness analyses cannot dynamically capture herd effects. The objective of this study was to develop a methodology to allow herd effect associated with vaccinating children against seasonal influenza to be incorporated into static models evaluating the cost-effectiveness of influenza vaccination. Two previously published linear equations for approximation of herd effects in general were compared with the results of a structured literature review undertaken using PubMed searches to identify data on herd effects specific to influenza vaccination. A linear function was fitted to point estimates from the literature using the sum of squared residuals. The literature review identified 21 publications on 20 studies for inclusion. Six studies provided data on a mathematical relationship between effective vaccine coverage in subgroups and reduction of influenza infection in a larger unvaccinated population. These supported a linear relationship when effective vaccine coverage in a subgroup population was between 20% and 80%. Three studies evaluating herd effect at a community level, specifically induced by vaccinating children, provided point estimates for fitting linear equations. The fitted linear equation for herd protection in the target population for vaccination (children) was slightly less conservative than a previously published equation for herd effects in general. The fitted linear equation for herd protection in the non-target population was considerably less conservative than the previously published equation. This method of approximating herd effect requires simple adjustments to the annual baseline risk of influenza in static models: (1) for the age group targeted by the childhood vaccination strategy (i.e. children); and (2) for other age groups not targeted (e

Targeted outreach hepatitis B vaccination program in high-risk adults: The fundamental challenge of the last mile.

Science.gov (United States)

Mangen, M-J J; Stibbe, H; Urbanus, A; Siedenburg, E C; Waldhober, Q; de Wit, G A; van Steenbergen, J E

2017-05-31

The aim of this study was to evaluate the cost-effectiveness of the on-going decentralised targeted hepatitis B vaccination program for behavioural high-risk groups operated by regional public health services in the Netherlands since 1-November-2002. Target groups for free vaccination are men having sex with men (MSM), commercial sex workers (CSW) and hard drug users (HDU). Heterosexuals with a high partner change rate (HRP) were included until 1-November-2007. Based on participant, vaccination and serology data collected up to 31-December-2012, the number of participants and program costs were estimated. Observed anti-HBc prevalence was used to estimate the probability of susceptible individuals per risk-group to become infected with hepatitis B virus (HBV) in their remaining life. We distinguished two time-periods: 2002-2006 and 2007-2012, representing different recruitment strategies and target groups. Correcting for observed vaccination compliance, the number of future HBV-infections avoided was estimated per risk-group. By combining these numbers with estimates of life-years lost, quality-of-life losses and healthcare costs of HBV-infections - as obtained from a Markov model-, the benefit of the program was estimated for each risk-group separately. The overall incremental cost-effectiveness ratio of the program was €30,400/QALY gained, with effects and costs discounted at 1.5% and 4%, respectively. The program was more cost-effective in the first period (€24,200/QALY) than in the second period (€42,400/QALY). In particular, the cost-effectiveness for MSM decreased from €20,700/QALY to €47,700/QALY. This decentralised targeted HBV-vaccination program is a cost-effective intervention in certain unvaccinated high-risk adults. Saturation within the risk-groups, participation of individuals with less risky behaviour, and increased recruitment investments in the second period made the program less cost-effective over time. The project should therefore

Vaccines against poverty

Science.gov (United States)

MacLennan, Calman A.; Saul, Allan

2014-01-01

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

KISS1 can be used as a novel target for developing a DNA immunocastration vaccine in ram lambs.

Science.gov (United States)

Han, Yanguo; Liu, Guiqiong; Jiang, Xunping; Ijaz, Nabeel; Tesema, Birhanu; Xie, Guangyue

2015-02-04

KISS1 gene-encoding kisspeptins are critical for the onset of puberty and control of adult fertility. This study investigated whether KISS1 can be used as a novel target for immunocastration. Human KISS1 was fused with the HBsAg-S gene for constructing an antibiotic-free recombinant plasmid pKS-asd that coded for 31.168 kDa target fusion protein. Six male Hu sheep lambs were divided into two equal groups, treatment and control. The vaccine (1mg/ram lamb) prepared in saline solution was injected into lambs at weeks 0, 3 and 6 of the experiment, respectively. Vaccine efficacy was evaluated in terms of KISS1-specific IgG antibody response, serum testosterone levels, scrotal circumference, testicular weight, length and breadth, extent of testicular tissue damage, and sexual behaviour changes. The specific anti-KISS1 antibody titre in vaccinated animals was significantly higher than that in controls (pvaccinated animals showed lower serum testosterone level, testicular weight and length and smaller scrotal circumference than those in controls (pvaccinated animals was suppressed; sexual behaviours in vaccinated animals were significantly lower (pvaccine induced a strong antibody response and resulted in the suppression of gonadal function and sexual behaviour in animals, demonstrating that KISS1 can be used as a novel target for developing a DNA immunocastration vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Potential of nanoparticles for allergen-specific immunotherapy - use of silica nanoparticles as vaccination platform.

Science.gov (United States)

Scheiblhofer, Sandra; Machado, Yoan; Feinle, Andrea; Thalhamer, Josef; Hüsing, Nicola; Weiss, Richard

2016-12-01

Allergen-specific immunotherapy is the only curative approach for the treatment of allergies. There is an urgent need for improved therapies, which increase both, efficacy and patient compliance. Novel routes of immunization and the use of more advanced vaccine platforms have gained heightened interest in this field. Areas covered: The current status of allergen-specific immunotherapy is summarized and novel routes of immunization and their challenges in the clinics are critically discussed. The use of nanoparticles as novel delivery system for allergy vaccines is comprehensively reviewed. Specifically, the advantages of silica nanoparticles as vaccine carriers and adjuvants are summarized. Expert opinion: Future allergen-specific immunotherapy will combine engineered hypoallergenic vaccines with novel routes of administration, such as the skin. Due to their biodegradability, and the easiness to introduce surface modifications, silica nanoparticles are promising candidates for tailor-made vaccines. By covalently linking allergens and polysaccharides to silica nanoparticles, a versatile vaccination platform can be designed to specifically target antigen-presenting cells, render the formulation hypoallergenic, and introduce immunomodulatory functions. Combining potent skin vaccination methods, such as fractional laser ablation, with nanoparticle-based vaccines addresses all the requirements for safe and efficient therapy of allergic diseases.

Making vaccines "on demand": a potential solution for emerging pathogens and biodefense?

Science.gov (United States)

De Groot, Anne S; Einck, Leo; Moise, Leonard; Chambers, Michael; Ballantyne, John; Malone, Robert W; Ardito, Matthew; Martin, William

2013-09-01

The integrated US Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) has made great strides in strategic preparedness and response capabilities. There have been numerous advances in planning, biothreat countermeasure development, licensure, manufacturing, stockpiling and deployment. Increased biodefense surveillance capability has dramatically improved, while new tools and increased awareness have fostered rapid identification of new potential public health pathogens. Unfortunately, structural delays in vaccine design, development, manufacture, clinical testing and licensure processes remain significant obstacles to an effective national biodefense rapid response capability. This is particularly true for the very real threat of "novel pathogens" such as the avian-origin influenzas H7N9 and H5N1, and new coronaviruses such as hCoV-EMC. Conventional approaches to vaccine development, production, clinical testing and licensure are incompatible with the prompt deployment needed for an effective public health response. An alternative approach, proposed here, is to apply computational vaccine design tools and rapid production technologies that now make it possible to engineer vaccines for novel emerging pathogen and WMD biowarfare agent countermeasures in record time. These new tools have the potential to significantly reduce the time needed to design string-of-epitope vaccines for previously unknown pathogens. The design process-from genome to gene sequence, ready to insert in a DNA plasmid-can now be accomplished in less than 24 h. While these vaccines are by no means "standard," the need for innovation in the vaccine design and production process is great. Should such vaccines be developed, their 60-d start-to-finish timeline would represent a 2-fold faster response than the current standard.

An approximation of herd effect due to vaccinating children against seasonal influenza – a potential solution to the incorporation of indirect effects into static models

Science.gov (United States)

2013-01-01

Background Indirect herd effect from vaccination of children offers potential for improving the effectiveness of influenza prevention in the remaining unvaccinated population. Static models used in cost-effectiveness analyses cannot dynamically capture herd effects. The objective of this study was to develop a methodology to allow herd effect associated with vaccinating children against seasonal influenza to be incorporated into static models evaluating the cost-effectiveness of influenza vaccination. Methods Two previously published linear equations for approximation of herd effects in general were compared with the results of a structured literature review undertaken using PubMed searches to identify data on herd effects specific to influenza vaccination. A linear function was fitted to point estimates from the literature using the sum of squared residuals. Results The literature review identified 21 publications on 20 studies for inclusion. Six studies provided data on a mathematical relationship between effective vaccine coverage in subgroups and reduction of influenza infection in a larger unvaccinated population. These supported a linear relationship when effective vaccine coverage in a subgroup population was between 20% and 80%. Three studies evaluating herd effect at a community level, specifically induced by vaccinating children, provided point estimates for fitting linear equations. The fitted linear equation for herd protection in the target population for vaccination (children) was slightly less conservative than a previously published equation for herd effects in general. The fitted linear equation for herd protection in the non-target population was considerably less conservative than the previously published equation. Conclusions This method of approximating herd effect requires simple adjustments to the annual baseline risk of influenza in static models: (1) for the age group targeted by the childhood vaccination strategy (i.e. children); and (2

An approximation of herd effect due to vaccinating children against seasonal influenza – a potential solution to the incorporation of indirect effects into static models

Directory of Open Access Journals (Sweden)

Van Vlaenderen Ilse

2013-01-01

Full Text Available Abstract Background Indirect herd effect from vaccination of children offers potential for improving the effectiveness of influenza prevention in the remaining unvaccinated population. Static models used in cost-effectiveness analyses cannot dynamically capture herd effects. The objective of this study was to develop a methodology to allow herd effect associated with vaccinating children against seasonal influenza to be incorporated into static models evaluating the cost-effectiveness of influenza vaccination. Methods Two previously published linear equations for approximation of herd effects in general were compared with the results of a structured literature review undertaken using PubMed searches to identify data on herd effects specific to influenza vaccination. A linear function was fitted to point estimates from the literature using the sum of squared residuals. Results The literature review identified 21 publications on 20 studies for inclusion. Six studies provided data on a mathematical relationship between effective vaccine coverage in subgroups and reduction of influenza infection in a larger unvaccinated population. These supported a linear relationship when effective vaccine coverage in a subgroup population was between 20% and 80%. Three studies evaluating herd effect at a community level, specifically induced by vaccinating children, provided point estimates for fitting linear equations. The fitted linear equation for herd protection in the target population for vaccination (children was slightly less conservative than a previously published equation for herd effects in general. The fitted linear equation for herd protection in the non-target population was considerably less conservative than the previously published equation. Conclusions This method of approximating herd effect requires simple adjustments to the annual baseline risk of influenza in static models: (1 for the age group targeted by the childhood vaccination strategy

Human papillomavirus and vaccine-related perceptions among men who have sex with men: a systematic review.

Science.gov (United States)

Nadarzynski, Tom; Smith, Helen; Richardson, Daniel; Jones, Christina J; Llewellyn, Carrie D

2014-11-01

Targeted human papillomavirus (HPV) vaccine could prevent HPV-related cancers and genital warts among men who have sex with men (MSM). In order to develop effective vaccination programmes for MSM, it is crucial to understand their knowledge, beliefs about HPV and attitudes towards HPV vaccine. A systematic search of 10 databases examined articles investigating HPV knowledge and HPV-related perceptions among MSM. Each paper was assessed to identify potential research directions in the context of targeted HPV vaccination for MSM. We identified 16 studies that included 5185 MSM and conducted mainly in North America. Generally, participants were over 26 years old, had poor-to-moderate knowledge about HPV and were not concerned about HPV-related diseases. Over a half of MSM were willing to accept HPV vaccine, if offered. However, there was large variability in HPV vaccine acceptability, partially due to inconsistencies in methods of ascertainment but also different levels of HPV vaccine awareness. Despite several misconceptions and poor knowledge of HPV infection, MSM might be receptive to HPV vaccination. However, further research is needed to identify which factors contribute to potential vaccine uptake in hypothetical MSM-targeted HPV vaccination. Future studies need to target those MSM with little sexual experience, who would benefit most from HPV vaccination. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Vaccine stabilization: research, commercialization, and potential impact.

Science.gov (United States)

Kristensen, Debra; Chen, Dexiang; Cummings, Ray

2011-09-22

All vaccines are susceptible to damage by elevated temperatures and many are also damaged by freezing. The distribution, storage, and use of vaccines therefore present challenges that could be reduced by enhanced thermostability, with resulting improvements in vaccine effectiveness. Formulation and processing technologies exist that can improve the stability of vaccines at temperature extremes, however, customization is required for individual vaccines and results are variable. Considerations affecting decisions about stabilization approaches include development cost, manufacturing cost, and the ease of use of the final product. Public sector agencies can incentivize vaccine developers to prioritize stabilization efforts through advocacy and by implementing policies that increase demand for thermostable vaccines. Copyright © 2011 Elsevier Ltd. All rights reserved.

Herd Immunity to Ebolaviruses Is Not a Realistic Target for Current Vaccination Strategies

Directory of Open Access Journals (Sweden)

Stuart G. Masterson

2018-05-01

Full Text Available The recent West African Ebola virus pandemic, which affected >28,000 individuals increased interest in anti-Ebolavirus vaccination programs. Here, we systematically analyzed the requirements for a prophylactic vaccination program based on the basic reproductive number (R0, i.e., the number of secondary cases that result from an individual infection. Published R0 values were determined by systematic literature research and ranged from 0.37 to 20. R0s ≥ 4 realistically reflected the critical early outbreak phases and superspreading events. Based on the R0, the herd immunity threshold (Ic was calculated using the equation Ic = 1 − (1/R0. The critical vaccination coverage (Vc needed to provide herd immunity was determined by including the vaccine effectiveness (E using the equation Vc = Ic/E. At an R0 of 4, the Ic is 75% and at an E of 90%, more than 80% of a population need to be vaccinated to establish herd immunity. Such vaccination rates are currently unrealistic because of resistance against vaccinations, financial/logistical challenges, and a lack of vaccines that provide long-term protection against all human-pathogenic Ebolaviruses. Hence, outbreak management will for the foreseeable future depend on surveillance and case isolation. Clinical vaccine candidates are only available for Ebola viruses. Their use will need to be focused on health-care workers, potentially in combination with ring vaccination approaches.

Prevention of rotavirus gastroenteritis in infants and children: rotavirus vaccine safety, efficacy, and potential impact of vaccines

Directory of Open Access Journals (Sweden)

Aruna Chandran

2010-07-01

Full Text Available Aruna Chandran1, Sean Fitzwater1, Anjie Zhen2, Mathuram Santosham11Department of International Health, Division of Health Systems, 2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USAAbstract: Rotavirus infection is the most common cause of severe gastroenteritis globally, with greater than 86% of deaths occurring in low-income and middle-income countries. There are two rotavirus vaccines currently licensed in the United States and prequalified by the World Health Organization. RV1 is a monovalent attenuated human rotavirus strain, given orally in two doses. RV5 is a pentavalent human-bovine reassortant rotavirus vaccine, given orally in three doses. A third rotavirus vaccine, LLV, is a lamb rotavirus strain given orally as a single dose, which is currently available only in China. RV1 and RV5 have been shown to be highly efficacious in developed countries, and initial results from trials in Africa and Asia are promising as well. At least three other vaccines are in development, which are being developed by manufacturers of developing countries. Further studies are needed to clarify issues including administration of oral rotavirus vaccines with breastfeeding and other oral vaccines, and alterations in dosing schedule. Using new data on global diarrheal burden, rotavirus is estimated to cause 390,000 deaths in children younger than 5 years. Should rotavirus vaccines be introduced in the routine immunization programs of all countries, a potential of 170,000 deaths could be prevented annually. The largest impact on mortality would be seen in low-income and middle-income countries, despite poor immunization coverage and lower efficacy. Therefore, international efforts are needed to ensure that rotavirus vaccines reach the populations with highest burden of rotavirus disease.Keywords: vaccination, mortality, rotavirus, gastroenteritis

Schistosomiasis elimination strategies and potential role of a vaccine in achieving global health goals.

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Mo, Annie X; Agosti, Jan M; Walson, Judd L; Hall, B Fenton; Gordon, Lance

2014-01-01

In March 2013, the National Institute of Allergy and Infectious Diseases and the Bill and Melinda Gates Foundation co-sponsored a meeting entitled "Schistosomiasis Elimination Strategy and Potential Role of a Vaccine in Achieving Global Health Goals" to discuss the potential role of schistosomiasis vaccines and other tools in the context of schistosomiasis control and elimination strategies. It was concluded that although schistosomiasis elimination in some focal areas may be achievable through current mass drug administration programs, global control and elimination will face several significant scientific and operational challenges, and will require an integrated approach with other, additional interventions. These challenges include vector (snail) control; environmental modification; water, sanitation, and hygiene; and other future innovative tools such as vaccines. Defining a clear product development plan that reflects a vaccine strategy as complementary to the existing control programs to combat different forms of schistosomiasis will be important to develop a vaccine effectively.

Engineering synthetic vaccines using cues from natural immunity

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Irvine, Darrell J.; Swartz, Melody A.; Szeto, Gregory L.

2013-11-01

Vaccines aim to protect against or treat diseases through manipulation of the immune response, promoting either immunity or tolerance. In the former case, vaccines generate antibodies and T cells poised to protect against future pathogen encounter or attack diseased cells such as tumours; in the latter case, which is far less developed, vaccines block pathogenic autoreactive T cells and autoantibodies that target self tissue. Enormous challenges remain, however, as a consequence of our incomplete understanding of human immunity. A rapidly growing field of research is the design of vaccines based on synthetic materials to target organs, tissues, cells or intracellular compartments; to co-deliver immunomodulatory signals that control the quality of the immune response; or to act directly as immune regulators. There exists great potential for well-defined materials to further our understanding of immunity. Here we describe recent advances in the design of synthetic materials to direct immune responses, highlighting successes and challenges in prophylactic, therapeutic and tolerance-inducing vaccines.

Cytomegalovirus and immunotherapy: opportunistic pathogen, novel target for cancer and a promising vaccine vector.

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Quinn, Michael; Erkes, Dan A; Snyder, Christopher M

2016-02-01

Cytomegalovirus (CMV) is a β-herpesvirus that infects most people in the world and is almost always asymptomatic in the healthy host. However, CMV persists for life, requiring continuous immune surveillance to prevent disease and thus, CMV is a frequent complication in immune compromised patients. Many groups have been exploring the potential for adoptive T-cell therapies to control CMV reactivation as well as the progression of solid tumors harboring CMV. In addition, CMV itself is being explored as a vaccine vector for eliciting potent T-cell responses. This review will discuss key features of the basic biology of CMV-specific T cells as well as highlighting unanswered questions and ongoing work in the development of T-cell-based immunotherapies to target CMV.

Macrophage galactose-type C-type lectin receptor for DC targeting of antitumor glycopeptide vaccines

DEFF Research Database (Denmark)

Nuti, M; Zizzari, I; Napoletano, C

2011-01-01

e13528 Background: Dendritic cells (DCs) are the most potent antigen presenting cells and are employed in cancer vaccination. Several receptors are being studied in order to identif strategies to increase DCs activating capacity. The C-type lectin macrophage galactose type C-type lectin (MGL...... of IFNg and IL-2 secretion by both CD8 and CD4 T cells. CONCLUSIONS: These results demonstrate that MGL engagement profoundly affects DC plasticity inducing and directing a Th1 immune response. Moreover, MGL receptor expressed on human DC can be targeted by glycopeptide based vaccines with adjuvant...

Advances and challenges in malaria vaccine development.

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Crompton, Peter D; Pierce, Susan K; Miller, Louis H

2010-12-01

Malaria caused by Plasmodium falciparum remains a major public health threat, especially among children and pregnant women in Africa. An effective malaria vaccine would be a valuable tool to reduce the disease burden and could contribute to elimination of malaria in some regions of the world. Current malaria vaccine candidates are directed against human and mosquito stages of the parasite life cycle, but thus far, relatively few proteins have been studied for potential vaccine development. The most advanced vaccine candidate, RTS,S, conferred partial protection against malaria in phase II clinical trials and is currently being evaluated in a phase III trial in Africa. New vaccine targets need to be identified to improve the chances of developing a highly effective malaria vaccine. A better understanding of the mechanisms of naturally acquired immunity to malaria may lead to insights for vaccine development.

The Potential Impact of a Hepatitis C Vaccine for People Who Inject Drugs: Is a Vaccine Needed in the Age of Direct-Acting Antivirals?

Directory of Open Access Journals (Sweden)

Jack Stone

Full Text Available The advent of highly effective hepatitis C (HCV treatments has questioned the need for a vaccine to control HCV amongst people who inject drugs (PWID. However, high treatment costs and ongoing reinfection risk suggest it could still play a role. We compared the impact of HCV vaccination amongst PWID against providing HCV treatment.Dynamic HCV vaccination and treatment models among PWID were used to determine the vaccination and treatment rates required to reduce chronic HCV prevalence or incidence in the UK over 20 or 40 years. Projections considered a low (50% protection for 5 years, moderate (70% protection for 10 years or high (90% protection for 20 years efficacy vaccine. Sensitivities to various parameters were examined.To halve chronic HCV prevalence over 40 years, the low, moderate and high efficacy vaccines required annual vaccination rates (coverage after 20 years of 162 (72%, 77 (56% and 44 (38% per 1000 PWID, respectively. These vaccination rates were 16, 7.6 and 4.4 times greater than corresponding treatment rates. To halve prevalence over 20 years nearly doubled these vaccination rates (moderate and high efficacy vaccines only and the vaccination-to-treatment ratio increased by 20%. For all scenarios considered, required annual vaccination rates and vaccination-to-treatment ratios were at least a third lower to reduce incidence than prevalence. Baseline HCV prevalence had little effect on the vaccine's impact on prevalence or incidence, but substantially affected the vaccination-to-treatment ratios. Behavioural risk heterogeneity only had an effect if we assumed no transitions between high and low risk states and vaccinations were targeted or if PWID were high risk for their first year.Achievable coverage levels of a low efficacy prophylactic HCV vaccine could greatly reduce HCV transmission amongst PWID. Current high treatment costs ensure vaccination could still be an important intervention option.

Enhancement of the priming efficacy of DNA vaccines encoding dendritic cell-targeted antigens by synergistic toll-like receptor ligands

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Kornbluth Richard S

2009-08-01

Full Text Available Abstract Background Targeting of protein antigens to dendritic cells (DC via the DEC205 receptor enhances presentation of antigen-derived peptides on MHC-I and MHC-II molecules and, in the presence of costimulatory signals, antigen-specific immune responses. The immunogenicity and efficacy of DNA vaccination can also be enhanced by fusing the encoded antigen to single chain antibodies directed against DEC205. To further improve this strategy, we evaluated different toll-like receptor ligands (TLR and CD40 ligands (CD40L as adjuvants for DNA vaccines encoding a DEC205-single-chain antibody fused to the ovalbumin model antigen or HIV-1 Gag and assessed the priming efficacy of DNA in a DNA prime adenoviral vector boost immunization regimen. Results Mice were primed with the adjuvanted DEC-205 targeted DNA vaccines and boosted with adenoviral vectors encoding the same antigens. CD8+ T cell responses were determined after the adenoviral booster immunization, to determine how well the different DNA immunization regimens prime for the adenoviral boost. In the absence of adjuvants, targeting of DNA-encoded ovalbumin to DCs suppressed CD8+ T-cell responses after the adenoviral booster immunization. CD8+ T-cell responses to the DEC205 targeted DNA vaccines increased only slightly by adding either the TLR-9 ligand CpG, the TLR-3 ligand Poly I:C, or CD40 ligand expression plasmids. However, the combination of both TLR-ligands led to a strong enhancement of CD8+ T-cell responses compared to a non-targeted DNA vaccine. This finding was confirmed using HIV Gag as antigen. Conclusion Although DNA prime adenoviral vector boost immunizations belong to the strongest inducers of cytotoxic T cell responses in different animal models and humans, the CD8+ T cell responses can be further improved by targeting the DNA encoded antigen to DEC205 in the presence of synergistic TLR ligands CpG and Poly I:C.

Controlled and targeted release of antigens by intelligent shell for improving applicability of oral vaccines.

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Zhang, Lei; Zeng, Zhanzhuang; Hu, Chaohua; Bellis, Susan L; Yang, Wendi; Su, Yintao; Zhang, Xinyan; Wu, Yunkun

2016-01-01

Conventional oral vaccines with simple architecture face barriers with regard to stimulating effective immunity. Here we describe oral vaccines with an intelligent phase-transitional shielding layer, poly[(methyl methacrylate)-co-(methyl acrylate)-co-(methacrylic acid)]-poly(D,L-lactide-co-glycolide) (PMMMA-PLGA), which can protect antigens in the gastro-intestinal tract and achieve targeted vaccination in the large intestine. With the surface immunogenic protein (SIP) from group B Streptococcus (GBS) entrapped as the antigen, oral administration with PMMMA-PLGA (PTRBL)/Trx-SIP nanoparticles stimulated robust immunity in tilapia, an animal with a relatively simple immune system. The vaccine succeeded in protecting against Streptococcus agalactiae, a pathogen of worldwide importance that threatens human health and is transmitted in water with infected fish. After oral vaccination with PTRBL/Trx-SIP, tilapia produced enhanced levels of SIP specific antibodies and displayed durability of immune protection. 100% of the vaccinated tilapia were protected from GBS infection, whereas the control groups without vaccines or vaccinated with Trx-SIP only exhibited respective infection rates of 100% or >60% within the initial 5 months after primary vaccination. Experiments in vivo demonstrated that the recombinant antigen Trx-SIP labeled with FITC was localized in colon, spleen and kidney, which are critical sites for mounting an immune response. Our results revealed that, rather than the size of the nanoparticles, it is more likely that the negative charge repulsion produced by ionization of the carboxyl groups in PMMMA shielded the nanoparticles from uptake by small intestinal epithelial cells. This system resolves challenges arising from gastrointestinal damage to antigens, and more importantly, offers a new approach applicable for oral vaccination. Copyright © 2015 Elsevier Ltd. All rights reserved.

Vaccine-preventable diseases and vaccination rates in South Dakota.

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Kightlinger, Lon

2013-01-01

Vaccine-preventable diseases have historically caused much illness and death in South Dakota. Sixty-seven diphtheria deaths were reported in 1892 and 1,017 polio cases were reported at the peak of the polio epidemic in 1952. As vaccines have been developed, licensed and put into wide use, the rates of diphtheria, polio, measles, smallpox and other diseases have successfully decreased leading to control, statewide elimination or eradication. Other diseases, such as pertussis, have been more difficult to control by vaccination alone. Although current vaccination coverage rates for South Dakota's kindergarten children surpass the Healthy People 2020 targets of 95 percent, the coverage rates for 2-year-old children and teenagers are below the target rates. Until vaccine-preventable diseases are eradicated globally, we must vigilantly maintain high vaccination coverage rates and aggressively apply control measures to limit transmission when diseases do occur in South Dakota.

Immunogenicity of two adjuvant formulations of an inactivated African horse sickness vaccine in guinea-pigs and target animals

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Gaetano Federico Ronchi

2012-03-01

Full Text Available Monovalent, inactivated and adjuvanted vaccines against African horse sickness, prepared with serotypes 5 and 9, were tested on guinea-pigs to select the formulation that offered the greatest immunity. The final formulation of the vaccines took into account the immune response in the guinea-pig and the inflammatory properties of two types of adjuvant previously tested on target animals. A pilot study was subsequently conducted on horses using a vaccine prepared with serotype 9. The vaccine stimulated neutralising antibodies from the first administration and, after the booster dose, 28 days later; high antibody levels were recorded for at least 10 months. The guinea-pig appears to be a useful laboratory model for the evaluation of the antigenic properties of African horse sickness vaccines.

Universal or Specific? A Modeling-Based Comparison of Broad-Spectrum Influenza Vaccines against Conventional, Strain-Matched Vaccines.

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Rahul Subramanian

2016-12-01

Full Text Available Despite the availability of vaccines, influenza remains a major public health challenge. A key reason is the virus capacity for immune escape: ongoing evolution allows the continual circulation of seasonal influenza, while novel influenza viruses invade the human population to cause a pandemic every few decades. Current vaccines have to be updated continually to keep up to date with this antigenic change, but emerging 'universal' vaccines-targeting more conserved components of the influenza virus-offer the potential to act across all influenza A strains and subtypes. Influenza vaccination programmes around the world are steadily increasing in their population coverage. In future, how might intensive, routine immunization with novel vaccines compare against similar mass programmes utilizing conventional vaccines? Specifically, how might novel and conventional vaccines compare, in terms of cumulative incidence and rates of antigenic evolution of seasonal influenza? What are their potential implications for the impact of pandemic emergence? Here we present a new mathematical model, capturing both transmission dynamics and antigenic evolution of influenza in a simple framework, to explore these questions. We find that, even when matched by per-dose efficacy, universal vaccines could dampen population-level transmission over several seasons to a greater extent than conventional vaccines. Moreover, by lowering opportunities for cross-protective immunity in the population, conventional vaccines could allow the increased spread of a novel pandemic strain. Conversely, universal vaccines could mitigate both seasonal and pandemic spread. However, where it is not possible to maintain annual, intensive vaccination coverage, the duration and breadth of immunity raised by universal vaccines are critical determinants of their performance relative to conventional vaccines. In future, conventional and novel vaccines are likely to play complementary roles in

Evaluating human papillomavirus vaccination programs in Canada: should provincial healthcare pay for voluntary adult vaccination?

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Smith? Robert J

2008-04-01

Full Text Available Abstract Background Recently, provincial health programs in Canada and elsewhere have begun rolling out vaccination against human papillomavirus for girls aged 9–13. While vaccination is voluntary, the cost of vaccination is waived, to encourage parents to have their daughters vaccinated. Adult women who are eligible for the vaccine may still receive it, but at a cost of approximately CAN$400. Given the high efficacy and immunogenicity of the vaccine, the possibility of eradicating targeted types of the virus may be feasible, assuming the vaccination programs are undertaken strategically. Methods We develop a mathematical model to describe the epidemiology of vaccination against human papillomavirus, accounting for a widespread childhood vaccination program that may be supplemented by voluntary adult vaccination. A stability analysis is performed to determine the stability of the disease-free equilibrium. The critical vaccine efficacy and immunogenicity thresholds are derived, and the minimum level of adult vaccination required for eradication of targeted types is determined. Results We demonstrate that eradication of targeted types is indeed feasible, although the burden of coverage for a childhood-only vaccination program may be high. However, if a small, but non-negligible, proportion of eligible adults can be vaccinated, then the possibility of eradication of targeted types becomes much more favourable. We provide a threshold for eradication in general communities and illustrate the results with numerical simulations. We also investigate the effects of suboptimal efficacy and immunogenicity and show that there is a critical efficacy below which eradication of targeted types is not possible. If eradication is possible, then there is a critical immunogenicity such that even 100% childhood vaccination will not eradicate the targeted types of the virus and must be supplemented with voluntary adult vaccination. However, the level of adult

Low and decreasing vaccine effectiveness against influenza A(H3) in 2011/12 among vaccination target groups in Europe: results from the I-MOVE multicentre case-control study.

LENUS (Irish Health Repository)

Kissling, E

2013-01-01

Within the Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) project we conducted a multicentre case–control study in eight European Union (EU) Member States to estimate the 2011\\/12 influenza vaccine effectiveness against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza A(H3) among the vaccination target groups. Practitioners systematically selected ILI \\/ acute respiratory infection patients to swab within seven days of symptom onset. We restricted the study population to those meeting the EU ILI case definition and compared influenza A(H3) positive to influenza laboratory-negative patients. We used logistic regression with study site as fixed effect and calculated adjusted influenza vaccine effectiveness (IVE), controlling for potential confounders (age group, sex, month of symptom onset, chronic diseases and related hospitalisations, number of practitioner visits in the previous year). Adjusted IVE was 25% (95% confidence intervals (CI): -6 to 47) among all ages (n=1,014), 63% (95% CI: 26 to 82) in adults aged between 15 and 59 years and 15% (95% CI: -33 to 46) among those aged 60 years and above. Adjusted IVE was 38% (95%CI: -8 to 65) in the early influenza season (up to week 6 of 2012) and -1% (95% CI: -60 to 37) in the late phase. The results suggested a low adjusted IVE in 2011\\/12. The lower IVE in the late season could be due to virus changes through the season or waning immunity. Virological surveillance should be enhanced to quantify change over time and understand its relation with duration of immunological protection. Seasonal influenza vaccines should be improved to achieve acceptable levels of protection.

Development of an enhanced bovine viral diarrhea virus subunit vaccine based on E2 glycoprotein fused to a single chain antibody which targets to antigen-presenting cells

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Andrea Pecora

2015-03-01

Full Text Available Bovine viral diarrhea virus (BVDV is an important cause of economic losses worldwide. E2 is an immunodominant protein and a promising candidate to develop subunit vaccines. To improve its immunogenicity, a truncated E2 (tE2 was fused to a single chain antibody named APCH, which targets to antigen-presenting cells. APCH-tE2 and tE2 proteins were expressed in the baculovirus system and their immunogenicity was firstly compared in guinea pigs. APCH-tE2 vaccine was the best one to evoke a humoral response, and for this reason, it was selected for a cattle vaccination experiment. All the bovines immunized with 1.5 µg of APCH-tE2 developed high levels of neutralizing antibodies against BVDV up to a year post-immunization, demonstrating its significant potential as a subunit vaccine. This novel vaccine is undergoing scale-up and was transferred to the private sector. Nowadays, it is being evaluated for registration as the first Argentinean subunit vaccine for cattle.

Vaccines 'on demand': science fiction or a future reality.

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Ulmer, Jeffrey B; Mansoura, Monique K; Geall, Andrew J

2015-02-01

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.

Vaccinomics Approach for Designing Potential Peptide Vaccine by Targeting Shigella spp. Serine Protease Autotransporter Subfamily Protein SigA

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Arafat Rahman Oany

2017-01-01

Full Text Available Shigellosis, a bacillary dysentery, is closely associated with diarrhoea in human and causes infection of 165 million people worldwide per year. Casein-degrading serine protease autotransporter of enterobacteriaceae (SPATE subfamily protein SigA, an outer membrane protein, exerts both cytopathic and enterotoxic effects especially cytopathic to human epithelial cell type-2 (HEp-2 and is shown to be highly immunogenic. In the present study, we have tried to impose the vaccinomics approach for designing a common peptide vaccine candidate against the immunogenic SigA of Shigella spp. At first, 44 SigA proteins from different variants of S. flexneri, S. dysenteriae, S. boydii, and S. sonnei were assessed to find the most antigenic protein. We retrieved 12 peptides based on the highest score for human leukocyte antigen (HLA supertypes analysed by NetCTL. Initially, these peptides were assessed for the affinity with MHC class I and class II alleles, and four potential core epitopes VTARAGLGY, FHTVTVNTL, HTTWTLTGY, and IELAGTLTL were selected. From these, FHTVTVNTL and IELAGTLTL peptides were shown to have 100% conservancy. Finally, IELAGTLTL was shown to have the highest population coverage (83.86% among the whole world population. In vivo study of the proposed epitope might contribute to the development of functional and unique widespread vaccine, which might be an operative alleyway to thwart dysentery from the world.

Sieve analysis in HIV-1 vaccine efficacy trials.

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Edlefsen, Paul T; Gilbert, Peter B; Rolland, Morgane

2013-09-01

The genetic characterization of HIV-1 breakthrough infections in vaccine and placebo recipients offers new ways to assess vaccine efficacy trials. Statistical and sequence analysis methods provide opportunities to mine the mechanisms behind the effect of an HIV vaccine. The release of results from two HIV-1 vaccine efficacy trials, Step/HVTN-502 (HIV Vaccine Trials Network-502) and RV144, led to numerous studies in the last 5 years, including efforts to sequence HIV-1 breakthrough infections and compare viral characteristics between the vaccine and placebo groups. Novel genetic and statistical analysis methods uncovered features that distinguished founder viruses isolated from vaccinees from those isolated from placebo recipients, and identified HIV-1 genetic targets of vaccine-induced immune responses. Studies of HIV-1 breakthrough infections in vaccine efficacy trials can provide an independent confirmation to correlates of risk studies, as they take advantage of vaccine/placebo comparisons, whereas correlates of risk analyses are limited to vaccine recipients. Through the identification of viral determinants impacted by vaccine-mediated host immune responses, sieve analyses can shed light on potential mechanisms of vaccine protection.

Insight into the potential for DNA idiotypic fusion vaccines designed for patients by analysing xenogeneic anti-idiotypic antibody responses

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Forconi, Francesco; King, Catherine A; Sahota, Surinder S; Kennaway, Christopher K; Russell, Nigel H; Stevenson, Freda K

2002-01-01

DNA vaccines induce immune responses against encoded proteins, and have clear potential for cancer vaccines. For B-cell tumours, idiotypic (Id) immunoglobulin encoded by the variable region genes provides a target antigen. When assembled as single chain Fv (scFv), and fused to an immunoenhancing sequence from tetanus toxin (TT), DNA fusion vaccines induce anti-Id antibodies. In lymphoma models, these antibodies have a critical role in mediating protection. For application to patients with lymphoma, two questions arise: first, whether pre-existing antibody against TT affects induction of anti-scFv antibodies; second, whether individual human scFv fusion sequences are able to fold consistently to generate antibodies able to recognize private conformational Id determinants expressed by tumour cells. Using xenogeneic vaccination with scFv sequences from four patients, we have shown that pre-existing anti-TT immunity slows, but does not prevent, anti-Id antibody responses. To determine folding, we have monitored the ability of nine DNAscFv–FrC patients' vaccines to induce xenogeneic anti-Id antibodies. Antibodies were induced in all cases, and were strikingly specific for each patient's immunoglobulin with little cross-reactivity between patients, even when similar VH or VL genes were involved. Blocking experiments with human serum confirmed reactivity against private determinants in 26–97% of total antibody. Both immunoglobulin G1 (IgG1) and IgG2a subclasses were present at 1·3 : 1–15 : 1 consistent with a T helper 2-dominated response. Xenogeneic vaccination provides a simple route for testing individual patients' DNAscFv–FrC fusion vaccines, and offers a strategy for production of anti-Id antibodies. The findings underpin the approach of DNA idiotypic fusion vaccination for patients with B-cell tumours. PMID:12225361

Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model.

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Germain J P Fernando

Full Text Available BACKGROUND: Over 14 million people die each year from infectious diseases despite extensive vaccine use [1]. The needle and syringe--first invented in 1853--is still the primary delivery device, injecting liquid vaccine into muscle. Vaccines could be far more effective if they were precisely delivered into the narrow layer just beneath the skin surface that contains a much higher density of potent antigen-presenting cells (APCs essential to generate a protective immune response. We hypothesized that successful vaccination could be achieved this way with far lower antigen doses than required by the needle and syringe. METHODOLOGY/PRINCIPAL FINDINGS: To meet this objective, using a probability-based theoretical analysis for targeting skin APCs, we designed the Nanopatch, which contains an array of densely packed projections (21025/cm(2 invisible to the human eye (110 microm in length, tapering to tips with a sharpness of <1000 nm, that are dry-coated with vaccine and applied to the skin for two minutes. Here we show that the Nanopatches deliver a seasonal influenza vaccine (Fluvax 2008 to directly contact thousands of APCs, in excellent agreement with theoretical prediction. By physically targeting vaccine directly to these cells we induced protective levels of functional antibody responses in mice and also protection against an influenza virus challenge that are comparable to the vaccine delivered intramuscularly with the needle and syringe--but with less than 1/100(th of the delivered antigen. CONCLUSIONS/SIGNIFICANCE: Our results represent a marked improvement--an order of magnitude greater than reported by others--for injected doses administered by other delivery methods, without reliance on an added adjuvant, and with only a single vaccination. This study provides a proven mathematical/engineering delivery device template for extension into human studies--and we speculate that successful translation of these findings into humans could

A forecast of typhoid conjugate vaccine introduction and demand in typhoid endemic low- and middle-income countries to support vaccine introduction policy and decisions.

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Mogasale, Vittal; Ramani, Enusa; Park, Il Yeon; Lee, Jung Seok

2017-09-02

A Typhoid Conjugate Vaccine (TCV) is expected to acquire WHO prequalification soon, which will pave the way for its use in many low- and middle-income countries where typhoid fever is endemic. Thus it is critical to forecast future vaccine demand to ensure supply meets demand, and to facilitate vaccine policy and introduction planning. We forecasted introduction dates for countries based on specific criteria and estimated vaccine demand by year for defined vaccination strategies in 2 scenarios: rapid vaccine introduction and slow vaccine introduction. In the rapid introduction scenario, we forecasted 17 countries and India introducing TCV in the first 5 y of the vaccine's availability while in the slow introduction scenario we forecasted 4 countries and India introducing TCV in the same time period. If the vaccine is targeting infants in high-risk populations as a routine single dose, the vaccine demand peaks around 40 million doses per year under the rapid introduction scenario. Similarly, if the vaccine is targeting infants in the general population as a routine single dose, the vaccine demand increases to 160 million doses per year under the rapid introduction scenario. The demand forecast projected here is an upper bound estimate of vaccine demand, where actual demand depends on various factors such as country priorities, actual vaccine introduction, vaccination strategies, Gavi financing, costs, and overall product profile. Considering the potential role of TCV in typhoid control globally; manufacturers, policymakers, donors and financing bodies should work together to ensure vaccine access through sufficient production capacity, early WHO prequalification of the vaccine, continued Gavi financing and supportive policy.

Microneedle-mediated delivery of viral vectored vaccines.

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Zaric, Marija; Ibarzo Yus, Bárbara; Kalcheva, Petya Petrova; Klavinskis, Linda Sylvia

2017-10-01

Microneedle array platforms are a promising technology for vaccine delivery, due to their ease of administration with no sharp waste generated, small size, possibility of targeted delivery to the specified skin depth and efficacious delivery of different vaccine formulations, including viral vectors. Areas covered: Attributes and challenges of the most promising viral vector candidates that have advanced to the clinic and that have been leveraged for skin delivery by microneedles; The importance of understanding the immunobiology of antigen-presenting cells in the skin, in particular dendritic cells, in order to generate further improved skin vaccination strategies; recent studies where viral vectors expressing various antigens have been coupled with microneedle technology to examine their potential for improved vaccination. Expert opinion: Simple, economic and efficacious vaccine delivery methods are needed to improve health outcomes and manage possible outbreaks of new emerging viruses. Understanding what innate/inflammatory signals are required to induce both immediate and long-term responses remains a major hurdle in the development of the effective vaccines. One approach to meet these needs is microneedle-mediated viral vector vaccination. In order for this technology to fulfil this potential the industry must invest significantly to further develop its design, production, biosafety, delivery and large-scale manufacturing.

Live-attenuated tetravalent dengue vaccines: The needs and challenges of post-licensure evaluation of vaccine safety and effectiveness.

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Wichmann, Ole; Vannice, Kirsten; Asturias, Edwin J; de Albuquerque Luna, Expedito José; Longini, Ira; Lopez, Anna Lena; Smith, Peter G; Tissera, Hasitha; Yoon, In-Kyu; Hombach, Joachim

2017-10-09

Since December 2015, the first dengue vaccine has been licensed in several Asian and Latin American countries for protection against disease from all four dengue virus serotypes. While the vaccine demonstrated an overall good safety and efficacy profile in clinical trials, some key research questions remain which make risk-benefit-assessment for some populations difficult. As for any new vaccine, several questions, such as very rare adverse events following immunization, duration of vaccine-induced protection and effectiveness when used in public health programs, will be addressed by post-licensure studies and by data from national surveillance systems after the vaccine has been introduced. However, the complexity of dengue epidemiology, pathogenesis and population immunity, as well as some characteristics of the currently licensed vaccine, and potentially also future, live-attenuated dengue vaccines, poses a challenge for evaluation through existing monitoring systems, especially in low and middle-income countries. Most notable are the different efficacies of the currently licensed vaccine by dengue serostatus at time of first vaccination and by dengue virus serotype, as well as the increased risk of dengue hospitalization among young vaccinated children observed three years after the start of vaccination in one of the trials. Currently, it is unknown if the last phenomenon is restricted to younger ages or could affect also seronegative individuals aged 9years and older, who are included in the group for whom the vaccine has been licensed. In this paper, we summarize scientific and methodological considerations for public health surveillance and targeted post-licensure studies to address some key research questions related to live-attenuated dengue vaccines. Countries intending to introduce a dengue vaccine should assess their capacities to monitor and evaluate the vaccine's effectiveness and safety and, where appropriate and possible, enhance their surveillance

Development of an enhanced bovine viral diarrhea virus subunit vaccine based on E2 glycoprotein fused to a single chain antibody which targets to antigen-presenting cells.

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Pecora, Andrea; Malacari, Darío A; Pérez Aguirreburualde, María S; Bellido, Demian; Escribano, José M; Dus Santos, María J; Wigdorovitz, Andrés

2015-01-01

Bovine viral diarrhea virus (BVDV) is an important cause of economic losses worldwide. E2 is an immunodominant protein and a promising candidate to develop subunit vaccines. To improve its immunogenicity, a truncated E2 (tE2) was fused to a single chain antibody named APCH, which targets to antigen-presenting cells. APCH-tE2 and tE2 proteins were expressed in the baculovirus system and their immunogenicity was firstly compared in guinea pigs. APCH-tE2 vaccine was the best one to evoke a humoral response, and for this reason, it was selected for a cattle vaccination experiment. All the bovines immunized with 1.5 μg of APCH-tE2 developed high levels of neutralizing antibodies against BVDV up to a year post-immunization, demonstrating its significant potential as a subunit vaccine. This novel vaccine is undergoing scale-up and was transferred to the private sector. Nowadays, it is being evaluated for registration as the first Argentinean subunit vaccine for cattle. Copyright © 2014 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Nanoparticle-based B-cell targeting vaccines: Tailoring of humoral immune responses by functionalization with different TLR-ligands.

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Zilker, Claudia; Kozlova, Diana; Sokolova, Viktoriya; Yan, Huimin; Epple, Matthias; Überla, Klaus; Temchura, Vladimir

2017-01-01

Induction of an appropriate type of humoral immune response during vaccination is essential for protection against viral and bacterial infections. We recently observed that biodegradable calcium phosphate (CaP) nanoparticles coated with proteins efficiently targeted and activated naïve antigen-specific B-cells in vitro. We now compared different administration routes for CaP-nanoparticles and demonstrated that intramuscular immunization with such CaP-nanoparticles induced stronger immune responses than immunization with monovalent antigen. Additional functionalization of the CaP-nanoparticles with TRL-ligands allowed modulating the IgG subtype response and the level of mucosal IgA antibodies. CpG-containing CaP-nanoparticles were as immunogenic as a virus-like particle vaccine. Functionalization of CaP-nanoparticles with T-helper cell epitopes or CpG also allowed overcoming lack of T-cell help. Thus, our results indicate that CaP-nanoparticle-based B-cell targeting vaccines functionalized with TLR-ligands can serve as a versatile platform for efficient induction and modulation of humoral immune responses in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

Approved but non-funded vaccines: accessing individual protection.

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Scheifele, David W; Ward, Brian J; Halperin, Scott A; McNeil, Shelly A; Crowcroft, Natasha S; Bjornson, Gordean

2014-02-07

Funded immunization programs are best able to achieve high participation rates, optimal protection of the target population, and indirect protection of others. However, in many countries public funding of approved vaccines can be substantially delayed, limited to a portion of the at-risk population or denied altogether. In these situations, unfunded vaccines are often inaccessible to individuals at risk, allowing potentially avoidable morbidity and mortality to continue to occur. We contend that private access to approved but unfunded vaccines should be reconsidered and encouraged, with recognition that individuals have a prerogative to take advantage of a vaccine of potential benefit to them whether it is publicly funded or not. Moreover, numbers of "approved but unfunded" vaccines are likely to grow because governments will not be able to fund all future vaccines of potential benefit to some citizens. New strategies are needed to better use unfunded vaccines even though the net benefits will fall short of those of funded programs. Canada, after recent delays funding several new vaccine programs, has developed means to encourage private vaccine use. Physicians are required to inform relevant patients about risks and benefits of all recommended vaccines, publicly funded or not. Likewise, some provincial public health departments now recommend and promote both funded and unfunded vaccines. Pharmacists are key players in making unfunded vaccines locally available. Professional organizations are contributing to public and provider education about unfunded vaccines (e.g. herpes zoster, not funded in any province). Vaccine companies are gaining expertise with direct-to-consumer advertising. However, major challenges remain, such as making unfunded vaccines more available to low-income families and overcoming public expectations that all vaccines will be provided cost-free, when many other recommended personal preventive measures are user-pay. The greatest need is to

Potential impact of reactive vaccination in controlling cholera outbreaks: an exploratory analysis using a Zimbabwean experience.

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Kim, Sun-Young; Choi, Yeongchull; Mason, Peter R; Rusakaniko, Simbarashe; Goldie, Sue J

2011-09-05

To contain ongoing cholera outbreaks, the World Health Organization has suggested that reactive vaccination should be considered in addition to its previous control measures. To explore the potential impact of a hypothetical reactive oral cholera vaccination using the example of the recent large-scale cholera outbreak in Zimbabwe. This was a retrospective cost-effectiveness analysis calculating the health and economic burden of the cholera outbreak in Zimbabwe with and without reactive vaccination. The primary outcome measure was incremental cost per disability-adjusted life year (DALY) averted. Under the base-case assumptions (assuming 50% coverage among individuals aged ≥2 years), reactive vaccination could have averted 1 320 deaths and 23 650 DALYs. Considering herd immunity, the corresponding values would have been 2 920 deaths and 52 360 DALYs averted. The total vaccination costs would have been ~$74 million and ~$21 million, respectively, with per-dose vaccine price of US$5 and $1. The incremental costs per DALY averted of reactive vaccination were $2 770 and $370, respectively, for vaccine price set at $5 and $1. Assuming herd immunity, the corresponding cost was $980 with vaccine price of $5, and the programme was cost-saving with a vaccine price of $1. Results were most sensitive to case-fatality rate, per-dose vaccine price, and the size of the outbreak. Reactive vaccination has the potential to be a cost-effective measure to contain cholera outbreaks in countries at high risk. However, the feasibility of implementation should be further evaluated, and caution is warranted in extrapolating the findings to different settings in the absence of other in-depth studies.

The effects of anti-vaccine conspiracy theories on vaccination intentions.

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Daniel Jolley

Full Text Available The current studies investigated the potential impact of anti-vaccine conspiracy beliefs, and exposure to anti-vaccine conspiracy theories, on vaccination intentions. In Study 1, British parents completed a questionnaire measuring beliefs in anti-vaccine conspiracy theories and the likelihood that they would have a fictitious child vaccinated. Results revealed a significant negative relationship between anti-vaccine conspiracy beliefs and vaccination intentions. This effect was mediated by the perceived dangers of vaccines, and feelings of powerlessness, disillusionment and mistrust in authorities. In Study 2, participants were exposed to information that either supported or refuted anti-vaccine conspiracy theories, or a control condition. Results revealed that participants who had been exposed to material supporting anti-vaccine conspiracy theories showed less intention to vaccinate than those in the anti-conspiracy condition or controls. This effect was mediated by the same variables as in Study 1. These findings point to the potentially detrimental consequences of anti-vaccine conspiracy theories, and highlight their potential role in shaping health-related behaviors.

Vaccination against group B streptococcus.

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Heath, Paul T; Feldman, Robert G

2005-04-01

Streptococcus agalactiae (Group B streptococcus) is an important cause of disease in infants, pregnant women, the elderly and in immunosuppressed adults. An effective vaccine is likely to prevent the majority of infant disease (both early and late onset), as well as Group B streptococcus-related stillbirths and prematurity, to avoid the current real and theoretical limitations of intrapartum antibiotic prophylaxis, and to be cost effective. The optimal time to administer such a vaccine would be in the third trimester of pregnancy. The main limitations on the production of a Group B streptococcus vaccine are not technical or scientific, but regulatory and legal. A number of candidates including capsular conjugate vaccines using traditional carrier proteins such as tetanus toxoid and mutant diphtheria toxin CRM197, as well as Group B streptococcus-specific proteins such as C5a peptidase, protein vaccines using one or more Group B streptococcus surface proteins and mucosal vaccines, have the potential to be successful vaccines. The capsular conjugate vaccines using tetanus and CRM197 carrier proteins are the most advanced candidates, having already completed Phase II human studies including use in the target population of pregnant women (tetanus toxoid conjugate), however, no definitive protein conjugates have yet been trialed. However, unless the regulatory environment is changed specifically to allow the development of a Group B streptococcus vaccine, it is unlikely that one will ever reach the market.

Immune responses elicited by Mycoplasma hyopneumoniae recombinant antigens and DNA constructs with potential for use in vaccination against porcine enzootic pneumonia.

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Virginio, Veridiana Gomes; Gonchoroski, Taylor; Paes, Jéssica Andrade; Schuck, Desirée Cigaran; Zaha, Arnaldo; Ferreira, Henrique Bunselmeyer

2014-10-07

Mycoplasma hyopneumoniae is the etiological agent of porcine enzootic pneumonia (PEP) and causes major economic losses to the pig industry worldwide. Commercially available vaccines provide only partial protection and are relatively expensive. In this study, we assessed the humoral and cellular immune responses to three recombinant antigens of M. hyopneumoniae. Immune responses to selected domains of the P46, HSP70 and MnuA antigens (P46102-253, HSP70212-601 and MnuA182-378), delivered as recombinant subunit or DNA vaccines, were evaluated in BALB/c mice. All purified recombinant antigens and two DNA vaccines, pcDNA3.1(+)/HSP70212-601 and pcDNA3.1(+)/MnuA182-378, elicited a strong humoral immune response, indicated by high IgG levels in the serum. The cellular immune response was assessed by detection of IFN-γ, IL-10 and IL-4 in splenocyte culture supernatants. The recombinant subunit and DNA vaccines induced Th1-polarized immune responses, as evidenced by increased levels of IFN-γ. All recombinant subunit vaccines and the pcDNA3.1(+)/MnuA182-378 vaccine also induced the secretion of IL-10, a Th2-type cytokine, in large quantities. The mixed Th1/Th2-type response may elicit an effective immune response against M. hyopneumoniae, suggesting that P46102-253, HSP70212-601 and MnuA182-378 are potential novel and promising targets for the development of vaccines against PEP. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mechanism of ad5 vaccine immunity and toxicity: fiber shaft targeting of dendritic cells.

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Cheng Cheng

2007-02-01

Full Text Available Recombinant adenoviral (rAd vectors elicit potent cellular and humoral immune responses and show promise as vaccines for HIV-1, Ebola virus, tuberculosis, malaria, and other infections. These vectors are now widely used and have been generally well tolerated in vaccine and gene therapy clinical trials, with many thousands of people exposed. At the same time, dose-limiting adverse responses have been observed, including transient low-grade fevers and a prior human gene therapy fatality, after systemic high-dose recombinant adenovirus serotype 5 (rAd5 vector administration in a human gene therapy trial. The mechanism responsible for these effects is poorly understood. Here, we define the mechanism by which Ad5 targets immune cells that stimulate adaptive immunity. rAd5 tropism for dendritic cells (DCs was independent of the coxsackievirus and adenovirus receptor (CAR, its primary receptor or the secondary integrin RGD receptor, and was mediated instead by a heparin-sensitive receptor recognized by a distinct segment of the Ad5 fiber, the shaft. rAd vectors with CAR and RGD mutations did not infect a variety of epithelial and fibroblast cell types but retained their ability to transfect several DC types and stimulated adaptive immune responses in mice. Notably, the pyrogenic response to the administration of rAd5 also localized to the shaft region, suggesting that this interaction elicits both protective immunity and vector-induced fevers. The ability of replication-defective rAd5 viruses to elicit potent immune responses is mediated by a heparin-sensitive receptor that interacts with the Ad5 fiber shaft. Mutant CAR and RGD rAd vectors target several DC and mononuclear subsets and induce both adaptive immunity and toxicity. Understanding of these interactions facilitates the development of vectors that target DCs through alternative receptors that can improve safety while retaining the immunogenicity of rAd vaccines.

A DNA Vaccine Protects Human Immune Cells against Zika Virus Infection in Humanized Mice

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Guohua Yi

2017-11-01

Full Text Available A DNA vaccine encoding prM and E protein has been shown to induce protection against Zika virus (ZIKV infection in mice and monkeys. However, its effectiveness in humans remains undefined. Moreover, identification of which immune cell types are specifically infected in humans is unclear. We show that human myeloid cells and B cells are primary targets of ZIKV in humanized mice. We also show that a DNA vaccine encoding full length prM and E protein protects humanized mice from ZIKV infection. Following administration of the DNA vaccine, humanized DRAG mice developed antibodies targeting ZIKV as measured by ELISA and neutralization assays. Moreover, following ZIKV challenge, vaccinated animals presented virtually no detectable virus in human cells and in serum, whereas unvaccinated animals displayed robust infection, as measured by qRT-PCR. Our results utilizing humanized mice show potential efficacy for a targeted DNA vaccine against ZIKV in humans.

Vaccine potential of recombinant cathepsinL1G against Fasciola gigantica in mice.

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Changklungmoa, Narin; Phoinok, Natthacha; Yencham, Chonthicha; Sobhon, Prasert; Kueakhai, Pornanan

2016-08-15

In this study, we characterized and investigated the vaccine potential of FgCatL1G against Fasciola gigantica infection in mice. Recombinant mature FgCatL1G (rmFgCatL1G) was expressed in Escherichia coli BL21. The vaccination was performed in Imprinting Control Region (ICR) mice (n=10) by subcutaneous injection with 50μg of rmFgCatL1G combined with Freund's adjuvant. Two weeks after the second boost, mice were infected with 15 metacercariae by the oral route. The percents of protection of rmFgCatL1G vaccine were estimated to be 56.5% and 58.3% when compared with non vaccinated-infected and adjuvant-infected controls, respectively. Antibodies in the immune sera of vaccinated mice were shown by immunoblot to react with the native FgCatL1s in the extract of all stages of parasites and rmFgCatL1H, recombinant pro - FgCatL1 (rpFgCatL1). By immunohistochemistry, the immune sera also reacted with FgCatL1s in the caecal epithelial cells of the parasites. The levels of IgG1 and IgG2a in the immune sera, which are indicative of Th2 and Th1 immune responses, were also increased with IgG1 predominating. The levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in rmFgCatL1G-immunized group showed no significant difference from the control groups, but pathological lesions of livers in rmFgCatL1G-immunized group showed significant decrease when compared to the control groups. This study indicates that rmFgCatL1G has a vaccine potential against F. gigantica in mice, and this potential will be tested in larger livestock animals. Copyright © 2016 Elsevier B.V. All rights reserved.

Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines

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Masayuki Hayashi

2017-02-01

Full Text Available Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV, a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.

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

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

2014-01-01

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

Review on the effects of influenza vaccination during pregnancy on preterm births

OpenAIRE

Nunes, Marta C; Madhi, Shabir A

2015-01-01

Pregnant women are considered to be susceptible to severe influenza illness and are recommended as a priority group to be targeted for influenza vaccination in countries with vaccination programs. Increased rates of poor birth outcomes have also been temporally associated with influenza infection, especially when pandemics strains emerge. Even though the primary purpose for influenza vaccination during pregnancy is to decrease the risk of influenza infection in the women, other potential bene...

Vaccine Targeting of Subdominant CD8+ T Cell Epitopes Increases the Breadth of the T Cell Response upon Viral Challenge, but May Impair Immediate Virus Control

DEFF Research Database (Denmark)

Steffensen, Maria A; Pedersen, Louise Holm; Jahn, Marie Louise

2016-01-01

As a result of the difficulties in making efficient vaccines against genetically unstable viruses such as HIV, it has been suggested that future vaccines should preferentially target subdominant epitopes, the idea being that this should allow a greater breadth of the induced T cell response and, ...... a limitation of our model, but clearly our findings underscore the importance of carefully weighing the pros and cons of changes in epitope targeting before any implementation.......As a result of the difficulties in making efficient vaccines against genetically unstable viruses such as HIV, it has been suggested that future vaccines should preferentially target subdominant epitopes, the idea being that this should allow a greater breadth of the induced T cell response and......, hence, a greater efficiency in controlling escape variants. However, to our knowledge the evidence supporting this concept is limited at best. To improve upon this, we used the murine lymphocytic choriomeningitis virus model and adenoviral vectors to compare a vaccine expressing unmodified Ag...

Informing vaccine decision-making: A strategic multi-attribute ranking tool for vaccines-SMART Vaccines 2.0.

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Knobler, Stacey; Bok, Karin; Gellin, Bruce

2017-01-20

SMART Vaccines 2.0 software is being developed to support decision-making among multiple stakeholders in the process of prioritizing investments to optimize the outcomes of vaccine development and deployment. Vaccines and associated vaccination programs are one of the most successful and effective public health interventions to prevent communicable diseases and vaccine researchers are continually working towards expanding targets for communicable and non-communicable diseases through preventive and therapeutic modes. A growing body of evidence on emerging vaccine technologies, trends in disease burden, costs associated with vaccine development and deployment, and benefits derived from disease prevention through vaccination and a range of other factors can inform decision-making and investment in new and improved vaccines and targeted utilization of already existing vaccines. Recognizing that an array of inputs influences these decisions, the strategic multi-attribute ranking method for vaccines (SMART Vaccines 2.0) is in development as a web-based tool-modified from a U.S. Institute of Medicine Committee effort (IOM, 2015)-to highlight data needs and create transparency to facilitate dialogue and information-sharing among decision-makers and to optimize the investment of resources leading to improved health outcomes. Current development efforts of the SMART Vaccines 2.0 framework seek to generate a weighted recommendation on vaccine development or vaccination priorities based on population, disease, economic, and vaccine-specific data in combination with individual preference and weights of user-selected attributes incorporating valuations of health, economics, demographics, public concern, scientific and business, programmatic, and political considerations. Further development of the design and utility of the tool is being carried out by the National Vaccine Program Office of the Department of Health and Human Services and the Fogarty International Center of the

Induction of immunity to human immunodeficiency virus type-1 by vaccination.

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McElrath, M Juliana; Haynes, Barton F

2010-10-29

Recent findings have brought optimism that development of a successful human immunodeficiency virus type-1 (HIV-1) vaccine lies within reach. Studies of early events in HIV-1 infection have revealed when and where HIV-1 is potentially vulnerable to vaccine-targeted immune responses. With technical advances in human antibody production, clues about how antibodies recognize HIV-1 envelope proteins have uncovered new targets for immunogen design. A recent vaccine regimen has shown modest efficacy against HIV-1 acquisition. However, inducing long-term T and B cell memory and coping with HIV-1 diversity remain high priorities. Mediators of innate immunity may play pivotal roles in blocking infection and shaping immunity; vaccine strategies to capture these activities are under investigation. Challenges remain in integrating basic, preclinical and clinical research to improve predictions of types of immunity associated with vaccine efficacy, to apply these insights to immunogen design, and to accelerate evaluation of vaccine efficacy in persons at-risk for infection. Copyright © 2010 Elsevier Inc. All rights reserved.

Immunomodulators as adjuvants for vaccines and antimicrobial therapy.

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Nicholls, Erin F; Madera, Laurence; Hancock, Robert E W

2010-12-01

A highly effective strategy for combating infectious diseases is to enhance host defenses using immunomodulators, either preventatively, through vaccination, or therapeutically. The effectiveness of many vaccines currently in use is due in part to adjuvants, molecules that have little immunogenicity by themselves but which help enhance and appropriately skew the immune response to an antigen. The development of new vaccines necessitates the development of new types of adjuvants to ensure an appropriate immune response. Herein, we review commonly used vaccine adjuvants and discuss promising adjuvant candidates. We also discuss various other immunomodulators (namely cytokines, Toll-like receptor agonists, and host defense peptides) that are, or have potential to be, useful for antimicrobial therapies that exert their effects by boosting host immune responses rather than targeting pathogens directly.

Rotavirus vaccines

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Kang G

2006-01-01

Full Text Available Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several years. The first rotavirus vaccine licensed in the United States was withdrawn because of an association of the vaccine with intussusception. However, the need for a vaccine is greatest in the developing world, because the benefits of preventing deaths due to rotavirus disease are substantially greater than the risk of intussusception. Early vaccines were based on animal strains. More recently developed and licenced vaccines are either animal-human reassortants or are based on human strains. In India, two candidate vaccines are in the development process, but have not yet reached efficacy trials. Many challenges regarding vaccine efficacy and safety remain. In addition to completing clinical evaluations of vaccines in development in settings with the highest disease burden and virus diversity, there is also a need to consider alternative vaccine development strategies.

A Key Opinion Leaders Analysis of the Critical Success Factors for the Market Potential of Genetically Modified Vaccines

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Ramezanpour, B.; Kamphuis, Pim; Claassen, H.J.H.M.

2016-01-01

Conventional vaccines have been very successful in preventing and controlling many diseases. One of the next steps in vaccine innovation is the introduction of genetic modification, which provides various novel opportunities in the vaccine field. Although the market potential for conventional

Dendritic Cell-Based Adjuvant Vaccination Targeting Wilms’ Tumor 1 in Patients with Advanced Colorectal Cancer

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Shigetaka Shimodaira

2015-12-01

Full Text Available Despite significant recent advances in the development of immune checkpoint inhibitors, the treatment of advanced colorectal cancer involving metastasis to distant organs remains challenging. We conducted a phase I study to investigate the safety and immunogenicity of Wilms’ tumor (WT1 class I/II peptides-pulsed dendritic cell DC vaccination for patients with advanced colorectal cancer. Standard treatment comprising surgical resection and chemotherapy was followed by one course of seven biweekly administrations of 1–2 × 107 DCs with 1–2 KE of OK-432 (streptococcal preparation in three patients. Clinical efficacy was confirmed based on WT1 expression using immunohistochemistry on paraffin-embedded tissues and immune monitoring using tetramer analysis and enzyme-linked immunosorbent spot (ELISPOT assays. WT1 expression with human leukocyte antigen (HLA-class I molecules was detected in surgical resected tissues. Adverse reactions to DC vaccinations were tolerable under an adjuvant setting. WT1-specific cytotoxic T cells were detected by both modified WT1-peptide/HLA-A*24:02 tetramer analysis and/or interferon-γ-producing cells through the use of ELISPOT assays after the first DC vaccination. Immunity acquired from DC vaccination persisted for two years with prolonged disease-free and overall survival. The present study indicated that DC vaccination targeting WT1 demonstrated the safety and immunogenicity as an adjuvant therapy in patients with resectable advanced colorectal cancer.

Clinician and Parent Perspectives on Educational Needs for Increasing Adolescent HPV Vaccination.

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Widman, Christy A; Rodriguez, Elisa M; Saad-Harfouche, Frances; Twarozek, Annamaria Masucci; Erwin, Deborah O; Mahoney, Martin C

2018-04-01

Human papillomavirus (HPV)-related morbidity and mortality remain a significant public health burden despite the availability of HPV vaccines for cancer prevention. We engaged clinicians and parents to identify barriers and opportunities related to adolescent HPV vaccination within a focused geographic region. This mixed-method study design used an interviewer-administered semi-structured interview with clinicians (n = 52) and a written self-administered survey with similar items completed by parents (n = 54). Items focused on experiences, opinions, and ideas about HPV vaccine utilization in the clinical setting, family, and patient perceptions about HPV vaccination and potential future efforts to increase vaccine utilization. Quantitative items were analyzed using descriptive statistics, while qualitative content was analyzed thematically. Suggested solutions for achieving higher rates of HPV vaccination noted by clinicians included public health education, the removal of stigma associated with vaccines, media endorsements, and targeting parents as the primary focus of educational messages. Parents expressed the need for more information about HPV-related disease, HPV vaccines, vaccine safety, sexual concerns, and countering misinformation on social media. Results from this mixed-method study affirm that educational campaigns targeting both health care professionals and parents represent a key facilitator for promoting HPV vaccination; disease burden and cancer prevention emerged as key themes for this messaging.

An antivector vaccine protects against a lethal vector-borne pathogen.

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Milan Labuda

2006-04-01

Full Text Available Vaccines that target blood-feeding disease vectors, such as mosquitoes and ticks, have the potential to protect against the many diseases caused by vector-borne pathogens. We tested the ability of an anti-tick vaccine derived from a tick cement protein (64TRP of Rhipicephalus appendiculatus to protect mice against tick-borne encephalitis virus (TBEV transmitted by infected Ixodes ricinus ticks. The vaccine has a "dual action" in immunized animals: when infested with ticks, the inflammatory and immune responses first disrupt the skin feeding site, resulting in impaired blood feeding, and then specific anti-64TRP antibodies cross-react with midgut antigenic epitopes, causing rupture of the tick midgut and death of engorged ticks. Three parameters were measured: "transmission," number of uninfected nymphal ticks that became infected when cofeeding with an infected adult female tick; "support," number of mice supporting virus transmission from the infected tick to cofeeding uninfected nymphs; and "survival," number of mice that survived infection by tick bite and subsequent challenge by intraperitoneal inoculation of a lethal dose of TBEV. We show that one dose of the 64TRP vaccine protects mice against lethal challenge by infected ticks; control animals developed a fatal viral encephalitis. The protective effect of the 64TRP vaccine was comparable to that of a single dose of a commercial TBEV vaccine, while the transmission-blocking effect of 64TRP was better than that of the antiviral vaccine in reducing the number of animals supporting virus transmission. By contrast, the commercial antitick vaccine (TickGARD that targets only the tick's midgut showed transmission-blocking activity but was not protective. The 64TRP vaccine demonstrates the potential to control vector-borne disease by interfering with pathogen transmission, apparently by mediating a local cutaneous inflammatory immune response at the tick-feeding site.

Vaccines today, vaccines tomorrow: a perspective.

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Loucq, Christian

2013-01-01

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

Human Papillomavirus vaccination in general practice in France, three years after the implementation of a targeted vaccine recommendation based on age and sexual history : Targeted HPV vaccine recommendation in France

OpenAIRE

Thierry , Pascale; Lasserre , Andrea; Rossignol , Louise; Kernéis , Solen; Blaizeau , Fanette; Stheneur , Chantal; Blanchon , Thierry; Levy-Bruhl , Daniel; Hanslik , Thomas

2015-01-01

International audience; IntroductionIn France, vaccination against human papilloma virus (HPV) was recommended in 2007 for all 14-year-old girls as well as “catch-up” vaccination for girls between 15-23 years of age either before or within one year of becoming sexually active. We evaluated the vaccine coverage according to the eligibility for vaccination in a sample of young girls aged 14 to 23 years, who were seen in general practices. Patients and methodsA survey was proposed to 706 general...

Potential for Controlling Cholera Using a Ring Vaccination Strategy: Re-analysis of Data from a Cluster-Randomized Clinical Trial.

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Mohammad Ali

2016-09-01

Full Text Available Vaccinating a buffer of individuals around a case (ring vaccination has the potential to target those who are at highest risk of infection, reducing the number of doses needed to control a disease. We explored the potential vaccine effectiveness (VE of oral cholera vaccines (OCVs for such a strategy.This analysis uses existing data from a cluster-randomized clinical trial in which OCV or placebo was given to 71,900 participants in Kolkata, India, from 27 July to 10 September 2006. Cholera surveillance was then conducted on 144,106 individuals living in the study area, including trial participants, for 5 y following vaccination. First, we explored the risk of cholera among contacts of cholera patients, and, second, we measured VE among individuals living within 25 m of cholera cases between 8 and 28 d after onset of the index case. For the first analysis, individuals living around each index case identified during the 5-y period were assembled using a ring to define cohorts of individuals exposed to cholera index cases. An index control without cholera was randomly selected for each index case from the same population, matched by age group, and individuals living around each index control were assembled using a ring to define cohorts not exposed to cholera cases. Cholera attack rates among the exposed and non-exposed cohorts were compared using different distances from the index case/control to define the rings and different time frames to define the period at risk. For the VE analysis, the exposed cohorts were further stratified according to the level of vaccine coverage into high and low coverage strata. Overall VE was assessed by comparing the attack rates between high and low vaccine coverage strata irrespective of individuals' vaccination status, and indirect VE was assessed by comparing the attack rates among unvaccinated members between high and low vaccine coverage strata. Cholera risk among the cohort exposed to cholera cases was 5

Human Papillomavirus Vaccine as an Anti-cancer Vaccine: Collaborative Efforts to Promote HPV Vaccine in the National Comprehensive Cancer Control Program

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Townsend, Julie S.; Steele, C. Brooke; Hayes, Nikki; Bhatt, Achal; Moore, Angela R.

2018-01-01

Background Widespread use of the HPV vaccine has the potential to reduce incidence from HPV-associated cancers. However, vaccine uptake among adolescents remains well below the Healthy People 2020 targets. The Centers for Disease Control and Prevention (CDC)’s National Comprehensive Cancer Control Program awardees (NCCCP) are well positioned to work with immunization programs to increase vaccine uptake. Methods CDC’s chronic disease management information system was queried for objectives and activities associated with HPV vaccine that were reported by NCCCP awardees from 2013 – 2016 as part of program reporting requirements. A content analysis was conducted on the query results to categorize interventions according to strategies outlined in The Guide to Community Preventive Services and the 2014 President’s Cancer Panel report. Results Sixty-two percent of NCCCP awardees had planned or implemented at least one activity since 2013 to address low HPV vaccination coverage in their jurisdictions. Most NCCCP awardees (86%) reported community education activities, while 65% reported activities associated with provider education. Systems-based strategies such as client reminders or provider assessment and feedback were each reported by less than 25% of NCCCP awardees. Conclusion Many NCCCP awardees report planning or implementing activities to address low HPV vaccination coverage, often in conjunction with state immunization programs. NCCCP awardees can play a role in increasing HPV vaccination coverage through their cancer prevention and control expertise and access to partners in the health care community. PMID:28263672

The potential global market size and public health value of an HIV-1 vaccine in a complex global market.

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Marzetta, Carol A; Lee, Stephen S; Wrobel, Sandra J; Singh, Kanwarjit J; Russell, Nina; Esparza, José

2010-07-05

An effective HIV vaccine will be essential for the control of the HIV pandemic. This study evaluated the potential global market size and value of a hypothetical HIV vaccine and considered clade diversity, disease burden, partial prevention of acquisition, impact of a reduction in viral load resulting in a decrease in transmission and delay to treatment, health care system differences regarding access, and HIV screening and vaccination, across all public and private markets. Vaccine product profiles varied from a vaccine that would have no effect on preventing infection to a vaccine that would effectively prevent infection and reduce viral load. High disease burden countries (HDBC; HIV prevalence > or = 1%) were assumed to routinely vaccinate pre-sexually active adolescents (10 years old), whereas low disease burden countries (LDBC; HIV prevalence rate market value of $210 million to $2.7 billion, depending on the vaccine product profile. If one-time catch-up campaigns were included (11-14 years old for HDBC and higher risk groups for LDBC), the additional cumulative approximately 70-237 million doses were needed over a 10-year period with a potential market value of approximately $695 million to $13.4 billion, depending on the vaccine product profile. Market size and value varied across market segments with the majority of the value in high income countries and the majority of the demand in low income countries. However, the value of the potential market in low income countries is still significant with up to $550 million annually for routine vaccination only and up to $1.7 billion for a one-time only catch-up campaign in 11-14 years old. In the most detail to date, this study evaluated market size and value of a potential multi-clade HIV vaccine, accounting for differences in disease burden, product profile and health care complexities. These findings provide donors and suppliers highly credible new data to consider in their continued efforts to develop an HIV-1

Respiratory nanoparticle-based vaccines and challenges associated with animal models and translation.

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Renukaradhya, Gourapura J; Narasimhan, Balaji; Mallapragada, Surya K

2015-12-10

Vaccine development has had a huge impact on human health. However, there is a significant need to develop efficacious vaccines for several existing as well as emerging respiratory infectious diseases. Several challenges need to be overcome to develop efficacious vaccines with translational potential. This review focuses on two aspects to overcome some barriers - 1) the development of nanoparticle-based vaccines, and 2) the choice of suitable animal models for respiratory infectious diseases that will allow for translation. Nanoparticle-based vaccines, including subunit vaccines involving synthetic and/or natural polymeric adjuvants and carriers, as well as those based on virus-like particles offer several key advantages to help overcome the barriers to effective vaccine development. These include the ability to deliver combinations of antigens, target the vaccine formulation to specific immune cells, enable cross-protection against divergent strains, act as adjuvants or immunomodulators, allow for sustained release of antigen, enable single dose delivery, and potentially obviate the cold chain. While mouse models have provided several important insights into the mechanisms of infectious diseases, they are often a limiting step in translation of new vaccines to the clinic. An overview of different animal models involved in vaccine research for respiratory infections, with advantages and disadvantages of each model, is discussed. Taken together, advances in nanotechnology, combined with the right animal models for evaluating vaccine efficacy, has the potential to revolutionize vaccine development for respiratory infections. Copyright © 2015 Elsevier B.V. All rights reserved.

Protective antitumor activity induced by a fusion vaccine with murine ...

African Journals Online (AJOL)

Targeting angiogenesis is an effective strategy for anticancer therapy. The vascular endothelialcadherin (VE-cad) regulated angiogenesis is a potential target for anti-angiogenesis. Here, we develop a fusion vaccine plasmid DNA pSec-MBD2-VE-cad from VE-cad and murine beta defensin2 (MBD2) to induce immunity for ...

The Potential Cost Effectiveness of Different Dengue Vaccination Programmes in Malaysia: A Value-Based Pricing Assessment Using Dynamic Transmission Mathematical Modelling.

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Shafie, Asrul Akmal; Yeo, Hui Yee; Coudeville, Laurent; Steinberg, Lucas; Gill, Balvinder Singh; Jahis, Rohani; Amar-Singh Hss

2017-05-01

Dengue disease poses a great economic burden in Malaysia. This study evaluated the cost effectiveness and impact of dengue vaccination in Malaysia from both provider and societal perspectives using a dynamic transmission mathematical model. The model incorporated sensitivity analyses, Malaysia-specific data, evidence from recent phase III studies and pooled efficacy and long-term safety data to refine the estimates from previous published studies. Unit costs were valued in $US, year 2013 values. Six vaccination programmes employing a three-dose schedule were identified as the most likely programmes to be implemented. In all programmes, vaccination produced positive benefits expressed as reductions in dengue cases, dengue-related deaths, life-years lost, disability-adjusted life-years and dengue treatment costs. Instead of incremental cost-effectiveness ratios (ICERs), we evaluated the cost effectiveness of the programmes by calculating the threshold prices for a highly cost-effective strategy [ICER price of $US32.39 for programme 6 (highly cost effective up to $US14.15) and up to a price of $US100.59 for programme 1 (highly cost effective up to $US47.96) from the provider perspective. The cost-effectiveness analysis is sensitive to under-reporting, vaccine protection duration and model time horizon. Routine vaccination for a population aged 13 years with a catch-up cohort aged 14-30 years in targeted hotspot areas appears to be the best-value strategy among those investigated. Dengue vaccination is a potentially good investment if the purchaser can negotiate a price at or below the cost-effective threshold price.

APPROACHING THE TARGET: THE PATH TOWARDS AN EFFECTIVE MALARIA VACCINE

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Alberto L. García-Basteiro

2012-01-01

Full Text Available Eliciting an effective malaria vaccine has been the goal of the scientific community for many years. A malaria vaccine, added to existing tools and strategies, would further prevent and decrease the unacceptable malaria morbidity and mortality burden. Great progress has been made over the last decade, with some vaccine candidates in the clinical phases of development. The RTS,S malaria vaccine candidate, based on a recombinant P. falciparum protein, is the most advanced of such candidates, currently undergoing a large phase III trial. RTS,S has consistently shown an efficacy of around 50% against the first clinical episode of malaria, with protection in some cases extending up to 4 years of duration. Thus, it is hoped that this candidate vaccine will eventually become the first licensed malaria vaccine. This first vaccine against a human parasite is a groundbreaking achievement, but improved malaria vaccines conferring higher protection will be needed if the aspiration of malaria eradication is to be achieved

Designing Peptide-Based HIV Vaccine for Chinese

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Fan, Xiaojuan

2014-01-01

CD4+ T cells are central to the induction and maintenance of CD8+ T cell and antibody-producing B cell responses, and the latter are essential for the protection against disease in subjects with HIV infection. How to elicit HIV-specific CD4+ T cell responses in a given population using vaccines is one of the major areas of current HIV vaccine research. To design vaccine that targets specifically Chinese, we assembled a database that is comprised of sequences from 821 Chinese HIV isolates and 46 human leukocyte antigen (HLA) DR alleles identified in Chinese population. We then predicted 20 potential HIV epitopes using bioinformatics approaches. The combination of these 20 epitopes has a theoretical coverage of 98.1% of the population for both the prevalent HIV genotypes and also Chinese HLA-DR types. We suggest that testing this vaccine experimentally will facilitate the development of a CD4+ T cell vaccine especially catered for Chinese. PMID:25136573

Autoimmune connective tissue diseases and vaccination

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Ewa Więsik-Szewczyk

2015-12-01

Full Text Available The idea that infectious agents can induce autoimmune diseases in genetically susceptible subjects has been a matter of discussion for years. Moreover, increased incidence of autoimmune diseases and introduction of prophylactic vaccinations from early childhood suggest that these two trends are linked. In the medical literature and even non-professional media, case reports or events temporally related to vaccination are reported. It raises the issue of vaccination safety. In everyday practice medical professionals, physicians, rheumatologists and other specialists will be asked their opinion of vaccination safety. The decision should be made according to evidence-based medicine and the current state of knowledge. The purpose of this paper is to discuss a potential mechanism which links infections, vaccinations and autoimmunity. We present an overview of published case reports, especially of systemic connective tissue diseases temporally related to vaccination and results from case-nested studies. As yet, no conclusive evidence supports a causal relationship between vaccination and autoimmune diseases. It has to be determined whether the performed studies are sufficiently Epsteinasensitive to detect the link. The debate is ongoing, and new data may be required to explain the pathogenesis of autoimmunity. We would like to underscore the need for prophylactic vaccination in patients with autoimmune rheumatic diseases and to break down the myth that the vaccines are contraindicated in this target group.

An increasing, potentially measles-susceptible population over time after vaccination in Korea.

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Kang, Hae Ji; Han, Young Woo; Kim, Su Jin; Kim, You-Jin; Kim, A-Reum; Kim, Joo Ae; Jung, Hee-Dong; Eom, Hye Eun; Park, Ok; Kim, Sung Soon

2017-07-24

In Korea, measles occurs mainly in infants measles infection. Age-specific measles seroprevalence was evaluated by performing enzyme immunoassays and plaque reduction-neutralization tests on 3050 subjects aged 0-50years (birth cohort 1964-2014) and 480 subjects aged 2-30years (birth cohort 1984-2012). The overall seropositivity and measles antibody concentrations were 71.5% and 1366mIU/mL, respectively. Progressive decline in antibody levels and seropositivity were observed over time after vaccination in infants, adolescents, and young adults. The accumulation of potentially susceptible individuals in the population was confirmed by comparing data from 2010 and 2014 seroprevalence surveys. The statistical correlation between measles incidence and measles seronegativity was determined. Waning levels of measles antibodies with increasing time post-vaccination suggests that measles susceptibility is potentially increasing in Korea. This trend may be related to limitations of vaccine-induced immunity in the absence of natural boosting by the wild virus, compared to naturally acquired immunity triggered by measles infection. This study provides an important view into the current measles herd immunity in Korea. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Burden of disease associated with cervical cancer in malaysia and potential costs and consequences of HPV vaccination.

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Aljunid, S; Zafar, A; Saperi, S; Amrizal, M

2010-01-01

An estimated 70% of cervical cancers worldwide are attributable to persistent infection with human papillomaviruses (HPV) 16 and 18. Vaccination against HPV 16/18 has been shown to dramatically reduce the incidence of associated precancerous and cancerous lesions. The aims of the present analyses were, firstly, to estimate the clinical and economic burden of disease attributable to HPV in Malaysia and secondly, to estimate long-term outcomes associated with HPV vaccination using a prevalence-based modeling approach. In the first part of the analysis costs attributable to cervical cancer and precancerous lesions were estimated; epidemiologic data were sourced from the WHO GLOBOCAN database and Malaysian national data sources. In the second part, a prevalence-based model was used to estimate the potential annual number of cases of cervical cancer and precancerous lesions that could be prevented and subsequent HPV-related treatment costs averted with the bivalent (HPV 16/18) and the quadrivalent (HPV 16/18/6/11) vaccines, at the population level, at steady state. A vaccine efficacy of 98% was assumed against HPV types included in both vaccines. Effectiveness against other oncogenic HPV types was based on the latest results from each vaccine's respective clinical trials. In Malaysia there are an estimated 4,696 prevalent cases of cervical cancer annually and 1,372 prevalent cases of precancerous lesions, which are associated with a total direct cost of RM 39.2 million with a further RM 12.4 million in indirect costs owing to lost productivity. At steady state, vaccination with the bivalent vaccine was estimated to prevent 4,199 cervical cancer cases per year versus 3,804 cases for the quadrivalent vaccine. Vaccination with the quadrivalent vaccine was projected to prevent 1,721 cases of genital warts annually, whereas the annual number of cases remained unchanged with the bivalent vaccine. Furthermore, vaccination with the bivalent vaccine was estimated to avert RM 45

Poxvirus-vectored vaccines for rabies--a review.

Science.gov (United States)

Weyer, Jacqueline; Rupprecht, Charles E; Nel, Louis H

2009-11-27

Oral rabies vaccination of target reservoir species has proved to be one of the pillars of successful rabies elimination programs. The use of live attenuated rabies virus vaccines has been extensive but several limitations hamper its future use. A recombinant vaccinia-rabies vaccine has also been successfully used for the oral vaccination of several species. Nevertheless, its lack of efficacy in certain important rabies reservoirs and concerns on the use of this potent live virus as vaccine carrier (vector) impair the expansion of its use for new target species and new areas. Several attenuated and host-restricted poxvirus alternatives, which supposedly offer enhanced safety, have been investigated. Once again, efficacy in certain target species and innocuity through the oral route remain major limitations of these vaccines. Alternative recombinant vaccines using adenovirus as an antigen delivery vector have been extensively investigated and may provide an important addition to the currently available oral rabies vaccine repertoire, but are not the primary subject of this review.

Modeling the Potential for Vaccination to Diminish the Burden of Invasive Non-typhoidal Salmonella Disease in Young Children in Mali, West Africa.

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Kristin Bornstein

2017-02-01

Full Text Available In sub-Saharan Africa, systematic surveillance of young children with suspected invasive bacterial disease (e.g., septicemia, meningitis has revealed non-typhoidal Salmonella (NTS to be a major pathogen exhibiting high case fatality (~20%. Where infant vaccination against Haemophilus influenzae type b (Hib and Streptococcus pneumoniae has been introduced to prevent invasive disease caused by these pathogens, as in Bamako, Mali, their burden has decreased markedly. In parallel, NTS has become the predominant invasive bacterial pathogen in children aged <5 years. While NTS is believed to be acquired orally via contaminated food/water, epidemiologic studies have failed to identify the reservoir of infection or vehicles of transmission. This has precluded targeting food chain interventions to diminish disease transmission but conversely has fostered the development of vaccines to prevent invasive NTS (iNTS disease. We developed a mathematical model to estimate the potential impact of NTS vaccination programs in Bamako.A Markov chain transmission model was developed utilizing age-specific Bamako demographic data and hospital surveillance data for iNTS disease in children aged <5 years and assuming vaccine coverage and efficacy similar to the existing, successfully implemented, Hib vaccine. Annual iNTS hospitalizations and deaths in children <5 years, with and without a Salmonella Enteritidis/Salmonella Typhimurium vaccine, were the model's outcomes of interest. Per the model, high coverage/high efficacy iNTS vaccination programs would drastically diminish iNTS disease except among infants age <8 weeks.The public health impact of NTS vaccination shifts as disease burden, vaccine coverage, and serovar distribution vary. Our model shows that implementing an iNTS vaccine through an analogous strategy to the Hib vaccination program in Bamako would markedly reduce cases and deaths due to iNTS among the pediatric population. The model can be adjusted for

Virus-Like-Vaccines against HIV.

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Andersson, Anne-Marie C; Schwerdtfeger, Melanie; Holst, Peter J

2018-02-11

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 (VLP) vaccines have emerged as potent inducers of antibody and helper T cell responses, while replication-deficient viral vectors have yielded potent cytotoxic T cell responses. Here, we review the emerging concept of merging these two technologies into virus-like-vaccines (VLVs) for the targeting 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, is a distinct advantage over live-attenuated vaccines that must balance safety and immunogenicity. Previous studies have delivered VLVs encoded in modified Vaccinia Ankara vectors and we have developed the concept into a single-reading adenovirus-based technology capable of eliciting robust CD8⁺ and CD4⁺ T cells responses and trimer binding antibody responses. Such vaccines offer the potential to display the naturally produced immunogen directly and induce an integrated humoral and cellular immune response.

Population-level effect of potential HSV2 prophylactic vaccines on HIV incidence in sub-Saharan Africa

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Freeman, Esther E.; White, Richard G.; Bakker, Roel; Orroth, Kate K.; Weiss, Helen A.; Buvé, Anne; Hayes, Richard J.; Glynn, Judith R.

2009-01-01

Herpes simplex virus type-2 (HSV2) infection increases HIV transmission. We explore the impact of a potential prophylactic HSV2 vaccination on HIV incidence in Africa using STDSIM an individual-based model. A campaign that achieved 70% coverage over 5 years with a vaccine that reduced susceptibility to HSV2 acquisition and HSV2 reactivation by 75% for 10 years, reduced HIV incidence by 30–40% after 20 years (range 4–66%). Over 20 years, in most scenarios fewer than 100 vaccinations were required to avert one HIV infection. HSV2 vaccines could have a substantial impact on HIV incidence. Intensified efforts are needed to develop an effective HSV2 vaccine. PMID:19071187

Implementation research: reactive mass vaccination with single-dose oral cholera vaccine, Zambia.

Science.gov (United States)

Poncin, Marc; Zulu, Gideon; Voute, Caroline; Ferreras, Eva; Muleya, Clara Mbwili; Malama, Kennedy; Pezzoli, Lorenzo; Mufunda, Jacob; Robert, Hugues; Uzzeni, Florent; Luquero, Francisco J; Chizema, Elizabeth; Ciglenecki, Iza

2018-02-01

To describe the implementation and feasibility of an innovative mass vaccination strategy - based on single-dose oral cholera vaccine - to curb a cholera epidemic in a large urban setting. In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign - 2.31 United States dollars (US$) per dose - included the relatively low cost of local delivery - US$ 0.41 per dose. We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.

Burden of HPV-caused cancers in Denmark and the potential effect of HPV-vaccination

DEFF Research Database (Denmark)

Skorstengaard, Malene; Thamsborg, Lise Holst; Lynge, Elsebeth

2017-01-01

-caused cancers in women and men, and to evaluate the potential of HPV-vaccination in cancer control. Methods: Data were retrieved from the literature on population prevalence of high risk (HR) HPV, on HR HPV-prevalence and genotypes in HPV-related cancers, and on number of cytology samples in cervical screening...... were preventable with HPV vaccination. However, including screening prevented cervical cancers, the burden of cancers caused by HPV-infection would be 1300–2000 in women as compared to 234 in men. Conclusion: Taking screening prevented cervical cancers into account, the cancer control potential of HPV...

Characterization of recombinant yellow fever-dengue vaccine viruses with human monoclonal antibodies targeting key conformational epitopes.

Science.gov (United States)

Lecouturier, Valerie; Berry, Catherine; Saulnier, Aure; Naville, Sophie; Manin, Catherine; Girerd-Chambaz, Yves; Crowe, James E; Jackson, Nicholas; Guy, Bruno

2018-04-26

The recombinant yellow fever-17D-dengue virus, live, attenuated, tetravalent dengue vaccine (CYD-TDV) is licensed in several dengue-endemic countries. Although the vaccine provides protection against dengue, the level of protection differs by serotype and warrants further investigation. We characterized the antigenic properties of each vaccine virus serotype using highly neutralizing human monoclonal antibodies (hmAbs) that bind quaternary structure-dependent epitopes. Specifically, we monitored the binding of dengue virus-1 (DENV-1; 1F4), DENV-2 (2D22) or DENV-3 (5J7) serotype-specific or DENV-1-4 cross-reactive (1C19) hmAbs to the four chimeric yellow fever-dengue vaccine viruses (CYD-1-4) included in phase III vaccine formulations using a range of biochemical and functional assays (dot blot, ELISA, surface plasmon resonance and plaque reduction neutralization assays). In addition, we used the "classic" live, attenuated DENV-2 vaccine serotype, immature CYD-2 viruses and DENV-2 virus-like particles as control antigens for anti-serotype-2 reactivity. The CYD vaccine serotypes were recognized by each hmAbs with the expected specificity, moreover, surface plasmon resonance indicated a high functional affinity interaction with the CYD serotypes. In addition, the hmAbs provided similar protection against CYD and wild-type dengue viruses in the in vitro neutralization assay. Overall, these findings demonstrate that the four CYD viruses used in clinical trials display key conformational and functional epitopes targeted by serotype-specific and/or cross-reactive neutralizing human antibodies. More specifically, we showed that CYD-2 displays serotype- specific epitopes present only on the mature virus. This indicates that the CYD-TDV has the ability to elicit antibody specificities which are similar to those induced by the wild type DENV. Future investigations will be needed to address the nature of CYD-TDV-induced responses after vaccine administration, and how these

Analyses of Brucella pathogenesis, host immunity, and vaccine targets using systems biology and bioinformatics

Directory of Open Access Journals (Sweden)

Yongqun eHe

2012-02-01

Full Text Available Brucella is a Gram-negative, facultative intracellular bacterium that causes zoonotic brucellosis in humans and various animals. Out of ten classified Brucella species, B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. In the past decade, the mechanisms of Brucella pathogenesis and host immunity have been extensively investigated using the cutting edge systems biology and bioinformatics approaches. This article provides a comprehensive review of the applications of Omics (including genomics, transcriptomics, and proteomics and bioinformatics technologies for the analysis of Brucella pathogenesis, host immune responses, and vaccine targets. Based on more than 30 sequenced Brucella genomes, comparative genomics is able to identify gene variations among Brucella strains that help to explain host specificity and virulence differences among Brucella species. Diverse transcriptomics and proteomics gene expression studies have been conducted to analyze gene expression profiles of wild type Brucella strains and mutants under different laboratory conditions. High throughput Omics analyses of host responses to infections with virulent or attenuated Brucella strains have been focused on responses by mouse and cattle macrophages, bovine trophoblastic cells, mouse and boar splenocytes, and ram buffy coat. Differential serum responses in humans and rams to Brucella infections have been analyzed using high throughput serum antibody screening technology. The Vaxign reverse vaccinology has been used to predict many Brucella vaccine targets. More than 180 Brucella virulence factors and their gene interaction networks have been identified using advanced literature mining methods. The recent development of community-based Vaccine Ontology and Brucellosis Ontology provides an efficient way for Brucella data integration, exchange, and computer-assisted automated reasoning.

Analyses of Brucella Pathogenesis, Host Immunity, and Vaccine Targets using Systems Biology and Bioinformatics

Science.gov (United States)

He, Yongqun

2011-01-01

Brucella is a Gram-negative, facultative intracellular bacterium that causes zoonotic brucellosis in humans and various animals. Out of 10 classified Brucella species, B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. In the past decade, the mechanisms of Brucella pathogenesis and host immunity have been extensively investigated using the cutting edge systems biology and bioinformatics approaches. This article provides a comprehensive review of the applications of Omics (including genomics, transcriptomics, and proteomics) and bioinformatics technologies for the analysis of Brucella pathogenesis, host immune responses, and vaccine targets. Based on more than 30 sequenced Brucella genomes, comparative genomics is able to identify gene variations among Brucella strains that help to explain host specificity and virulence differences among Brucella species. Diverse transcriptomics and proteomics gene expression studies have been conducted to analyze gene expression profiles of wild type Brucella strains and mutants under different laboratory conditions. High throughput Omics analyses of host responses to infections with virulent or attenuated Brucella strains have been focused on responses by mouse and cattle macrophages, bovine trophoblastic cells, mouse and boar splenocytes, and ram buffy coat. Differential serum responses in humans and rams to Brucella infections have been analyzed using high throughput serum antibody screening technology. The Vaxign reverse vaccinology has been used to predict many Brucella vaccine targets. More than 180 Brucella virulence factors and their gene interaction networks have been identified using advanced literature mining methods. The recent development of community-based Vaccine Ontology and Brucellosis Ontology provides an efficient way for Brucella data integration, exchange, and computer-assisted automated reasoning. PMID:22919594

Anti-cancer vaccine therapy for hematologic malignancies: An evolving era.

Science.gov (United States)

Nahas, Myrna R; Rosenblatt, Jacalyn; Lazarus, Hillard M; Avigan, David

2018-02-15

The potential promise of therapeutic vaccination as effective therapy for hematologic malignancies is supported by the observation that allogeneic hematopoietic cell transplantation is curative for a subset of patients due to the graft-versus-tumor effect mediated by alloreactive lymphocytes. Tumor vaccines are being explored as a therapeutic strategy to re-educate host immunity to recognize and target malignant cells through the activation and expansion of effector cell populations. Via several mechanisms, tumor cells induce T cell dysfunction and senescence, amplifying and maintaining tumor cell immunosuppressive effects, resulting in failure of clinical trials of tumor vaccines and adoptive T cell therapies. The fundamental premise of successful vaccine design involves the introduction of tumor-associated antigens in the context of effective antigen presentation so that tolerance can be reversed and a productive response can be generated. With the increasing understanding of the role of both the tumor and tumor microenvironment in fostering immune tolerance, vaccine therapy is being explored in the context of immunomodulatory therapies. The most effective strategy may be to use combination therapies such as anti-cancer vaccines with checkpoint blockade to target critical aspects of this environment in an effort to prevent the re-establishment of tumor tolerance while limiting toxicity associated with autoimmunity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Visual Indicators on Vaccine Boxes as Early Warning Tools to Identify Potential Freeze Damage.

Science.gov (United States)

Angoff, Ronald; Wood, Jillian; Chernock, Maria C; Tipping, Diane

2015-07-01

The aim of this study was to determine whether the use of visual freeze indicators on vaccines would assist health care providers in identifying vaccines that may have been exposed to potentially damaging temperatures. Twenty-seven sites in Connecticut involved in the Vaccine for Children Program participated. In addition to standard procedures, visual freeze indicators (FREEZEmarker ® L; Temptime Corporation, Morris Plains, NJ) were affixed to each box of vaccine that required refrigeration but must not be frozen. Temperatures were monitored twice daily. During the 24 weeks, all 27 sites experienced triggered visual freeze indicator events in 40 of the 45 refrigerators. A total of 66 triggered freeze indicator events occurred in all 4 types of refrigerators used. Only 1 of the freeze events was identified by a temperature-monitoring device. Temperatures recorded on vaccine data logs before freeze indicator events were within the 35°F to 46°F (2°C to 8°C) range in all but 1 instance. A total of 46,954 doses of freeze-sensitive vaccine were stored at the time of a visual freeze indicator event. Triggered visual freeze indicators were found on boxes containing 6566 doses (14.0% of total doses). Of all doses stored, 14,323 doses (30.5%) were of highly freeze-sensitive vaccine; 1789 of these doses (12.5%) had triggered indicators on the boxes. Visual freeze indicators are useful in the early identification of freeze events involving vaccines. Consideration should be given to including these devices as a component of the temperature-monitoring system for vaccines.

Vaccine Platforms to Control Arenaviral Hemorrhagic Fevers.

Science.gov (United States)

Carrion, Ricardo; Bredenbeek, Peter; Jiang, Xiaohong; Tretyakova, Irina; Pushko, Peter; Lukashevich, Igor S

2012-11-20

Arenaviruses are rodent-borne emerging human pathogens. Diseases caused by these viruses, e.g., Lassa fever (LF) in West Africa and South American hemorrhagic fevers (HFs), are serious public health problems in endemic areas. We have employed replication-competent and replication-deficient strategies to design vaccine candidates potentially targeting different groups "at risk". Our leader LF vaccine candidate, the live reassortant vaccine ML29, is safe and efficacious in all tested animal models including non-human primates. In this study we showed that treatment of fatally infected animals with ML29 two days after Lassa virus (LASV) challenge protected 80% of the treated animals. In endemic areas, where most of the target population is poor and many live far from health care facilities, a single-dose vaccination with ML29 would be ideal solution. Once there is an outbreak, a fast-acting vaccine or post-exposure prophylaxis would be best. The 2(nd) vaccine technology is based on Yellow Fever (YF) 17D vaccine. We designed YF17D-based recombinant viruses expressing LASV glycoproteins (GP) and showed protective efficacy of these recombinants. In the current study we developed a novel technology to clone LASV nucleocapsid within YF17D C gene. Low immunogenicity and stability of foreign inserts must be addressed to design successful LASV/YFV bivalent vaccines to control LF and YF in overlapping endemic areas of West Africa. The 3(rd) platform is based on the new generation of alphavirus replicon virus-like-particle vectors (VLPV). Using this technology we designed VLPV expressing LASV GP with enhanced immunogenicity and bivalent VLPV expressing cross-reactive GP of Junin virus (JUNV) and Machupo virus (MACV), causative agents of Argentinian and Bolivian HF, respectively. A prime-boost regimen required for VLPV immunization might be practical for medical providers, military, lab personnel, and visitors in endemic areas.

Vaccination against hepatitis A and B in persons subject to homelessness in inner Sydney: vaccine acceptance, completion rates and immunogenicity.

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Poulos, Roslyn G; Ferson, Mark J; Orr, Karen J; McCarthy, Michele A; Botham, Susan J; Stern, Jerome M; Lucey, Adrienne

2010-04-01

To determine acceptance, completion rates and immunogenicity of the standard vaccination schedule for hepatitis A (HAV) and B (HBV) in persons subject to homelessness. A convenience sample of clients (n=201) attending a medical clinic for homeless and disadvantaged persons in Sydney was enrolled. Serological screening for HAV and HBV was undertaken. An appropriate vaccination program was instituted. Post-vaccination serology determined serological response. Although many clients had serological evidence of past infection, at least 138 (69%) clients had the potential to benefit from vaccination. For hepatitis A and B vaccinations, completion rates were 73% (73 of 100 clients) and 75% (69 of 92 clients), respectively; after vaccination, protective antibody was found in 98.2% (56 of 57) and 72% (36 of 50) of clients, respectively. A successful vaccination program can be mounted with a vulnerable population. We consider a clinic with a well-established history of acceptance and utilisation by the target group; a low staff turnover and regular clientele; inclusion of vaccination as part of routine client care; and counselling (part of pre- and post-serological testing) essential components in achieving good vaccination completion rates. © 2010 The Authors. Journal Compilation © 2010 Public Health Association of Australia.

CAF01 potentiates immune responses and efficacy of an inactivated influenza vaccine in ferrets.

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Cyril Jean-Marie Martel

Full Text Available Trivalent inactivated vaccines (TIV against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6'-dibehenate, CAF01 was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved the immunogenicity of the vaccine, with increased influenza-specific IgA and IgG levels. Additionally, CAF01 promoted cellular-mediated immunity as indicated by interferon-gamma expressing lymphocytes, measured by flow cytometry. CAF01 also enhanced the protection conferred by the vaccine by reducing the viral load measured in nasal washes by RT-PCR. Finally, CAF01 allowed for dose-reduction and led to higher levels of protection compared to TIV adjuvanted with a squalene emulsion. The data obtained in this human-relevant challenge model supports the potential of CAF01 in future influenza vaccines.

Quantifying the potential role of unmeasured confounders : the example of influenza vaccination

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Groenwold, R H H; Hoes, A W; Nichol, K L; Hak, E

2008-01-01

BACKGROUND: The validity of non-randomized studies using healthcare databases is often challenged because they lack information on potentially important confounders, such as functional health status and socioeconomic status. In a study quantifying the effects of influenza vaccination among

Surface display of Clonorchis sinensis enolase on Bacillus subtilis spores potentializes an oral vaccine candidate.

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Wang, Xiaoyun; Chen, Wenjun; Tian, Yanli; Mao, Qiang; Lv, Xiaoli; Shang, Mei; Li, Xuerong; Yu, Xinbing; Huang, Yan

2014-03-10

Clonorchis sinensis (C. sinensis) infections remain the common public health problem in freshwater fish consumption areas. New effective prevention strategies are still the urgent challenges to control this kind of foodborne infectious disease. The biochemical importance and biological relevance render C. sinensis enolase (Csenolase) as a potential vaccine candidate. In the present study, we constructed Escherichia coli/Bacillus subtilis shuttle genetic engineering system and investigated the potential of Csenolase as an oral vaccine candidate for C. sinensis prevention in different immunization routes. Our results showed that, compared with control groups, both recombinant Csenolase protein and nucleic acid could induce a mixed IgG1/IgG2a immune response when administrated subcutaneously (Psinensis infection. Csenolase derived oral vaccine conferred worm reduction rate and egg reduction rate at 60.07% (Psinensis prevention. Copyright © 2014 Elsevier Ltd. All rights reserved.

Superior control of HIV-1 replication by CD8+ T cells targeting conserved epitopes: implications for HIV vaccine design.

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Pratima Kunwar

Full Text Available A successful HIV vaccine will likely induce both humoral and cell-mediated immunity, however, the enormous diversity of HIV has hampered the development of a vaccine that effectively elicits both arms of the adaptive immune response. To tackle the problem of viral diversity, T cell-based vaccine approaches have focused on two main strategies (i increasing the breadth of vaccine-induced responses or (ii increasing vaccine-induced responses targeting only conserved regions of the virus. The relative extent to which set-point viremia is impacted by epitope-conservation of CD8(+ T cell responses elicited during early HIV-infection is unknown but has important implications for vaccine design. To address this question, we comprehensively mapped HIV-1 CD8(+ T cell epitope-specificities in 23 ART-naïve individuals during early infection and computed their conservation score (CS by three different methods (prevalence, entropy and conseq on clade-B and group-M sequence alignments. The majority of CD8(+ T cell responses were directed against variable epitopes (p<0.01. Interestingly, increasing breadth of CD8(+ T cell responses specifically recognizing conserved epitopes was associated with lower set-point viremia (r = - 0.65, p = 0.009. Moreover, subjects possessing CD8(+ T cells recognizing at least one conserved epitope had 1.4 log10 lower set-point viremia compared to those recognizing only variable epitopes (p = 0.021. The association between viral control and the breadth of conserved CD8(+ T cell responses may be influenced by the method of CS definition and sequences used to determine conservation levels. Strikingly, targeting variable versus conserved epitopes was independent of HLA type (p = 0.215. The associations with viral control were independent of functional avidity of CD8(+ T cell responses elicited during early infection. Taken together, these data suggest that the next-generation of T-cell based HIV-1 vaccines should focus

Epidemiology of HPV 16 and cervical cancer in Finland and the potential impact of vaccination: mathematical modelling analyses.

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Ruanne V Barnabas

2006-05-01

Full Text Available BACKGROUND: Candidate human papillomavirus (HPV vaccines have demonstrated almost 90%-100% efficacy in preventing persistent, type-specific HPV infection over 18 mo in clinical trials. If these vaccines go on to demonstrate prevention of precancerous lesions in phase III clinical trials, they will be licensed for public use in the near future. How these vaccines will be used in countries with national cervical cancer screening programmes is an important question. METHODS AND FINDINGS: We developed a transmission model of HPV 16 infection and progression to cervical cancer and calibrated it to Finnish HPV 16 seroprevalence over time. The model was used to estimate the transmission probability of the virus, to look at the effect of changes in patterns of sexual behaviour and smoking on age-specific trends in cancer incidence, and to explore the impact of HPV 16 vaccination. We estimated a high per-partnership transmission probability of HPV 16, of 0.6. The modelling analyses showed that changes in sexual behaviour and smoking accounted, in part, for the increase seen in cervical cancer incidence in 35- to 39-y-old women from 1990 to 1999. At both low (10% in opportunistic immunisation and high (90% in a national immunisation programme coverage of the adolescent population, vaccinating women and men had little benefit over vaccinating women alone. We estimate that vaccinating 90% of young women before sexual debut has the potential to decrease HPV type-specific (e.g., type 16 cervical cancer incidence by 91%. If older women are more likely to have persistent infections and progress to cancer, then vaccination with a duration of protection of less than 15 y could result in an older susceptible cohort and no decrease in cancer incidence. While vaccination has the potential to significantly reduce type-specific cancer incidence, its combination with screening further improves cancer prevention. CONCLUSIONS: HPV vaccination has the potential to

Impact of information on intentions to vaccinate in a potential epidemic: Swine-origin Influenza A (H1N1).

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Chanel, Olivier; Luchini, Stéphane; Massoni, Sébastien; Vergnaud, Jean-Christophe

2011-01-01

Vaccination campaigns to prevent the spread of epidemics are successful only if the targeted populations subscribe to the recommendations of health authorities. However, because compulsory vaccination is hardly conceivable in modern democracies, governments need to convince their populations through efficient and persuasive information campaigns. In the context of the swine-origin A (H1N1) 2009 pandemic, we use an interactive study among the general public in the South of France, with 175 participants, to explore what type of information can induce change in vaccination intentions at both aggregate and individual levels. We find that individual attitudes to vaccination are based on rational appraisal of the situation, and that it is information of a purely scientific nature that has the only significant positive effect on intention to vaccinate. Copyright © 2010 Elsevier Ltd. All rights reserved.

Introducing vaccination against serogroup B meningococcal disease: an economic and mathematical modelling study of potential impact.

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Christensen, Hannah; Hickman, Matthew; Edmunds, W John; Trotter, Caroline L

2013-05-28

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.

A brief history of vaccines & vaccination in India

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Chandrakant Lahariya

2014-01-01

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.

A brief history of vaccines & vaccination in India.

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Lahariya, Chandrakant

2014-04-01

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.

Profiling the Targets of Protective CD8+ T Cell Responses to Infection

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Joseph T. Bruder

2017-12-01

Full Text Available T cells are critical effectors of host immunity that target intracellular pathogens, such as the causative agents of HIV, tuberculosis, and malaria. The development of vaccines that induce effective cell-mediated immunity against such pathogens has proved challenging; for tuberculosis and malaria, many of the antigens targeted by protective T cells are not known. Here, we report a novel approach for screening large numbers of antigens as potential targets of T cells. Malaria provides an excellent model to test this antigen discovery platform because T cells are critical mediators of protection following immunization with live sporozoite vaccines and the specific antigen targets are unknown. We generated an adenovirus array by cloning 312 highly expressed pre-erythrocytic Plasmodium yoelii antigens into adenovirus vectors using high-throughput methodologies. The array was screened to identify antigen-specific CD8+ T cells induced by a live sporozoite vaccine regimen known to provide high levels of sterile protection mediated by CD8+ T cells. We identified 69 antigens that were targeted by CD8+ T cells induced by this vaccine regimen. The antigen that recalled the highest frequency of CD8+ T cells, PY02605, induced protective responses in mice, demonstrating proof of principle for this approach in identifying antigens for vaccine development.

Policy resistance undermines superspreader vaccination strategies for influenza.

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Chad R Wells

Full Text Available Theoretical models of infection spread on networks predict that targeting vaccination at individuals with a very large number of contacts (superspreaders can reduce infection incidence by a significant margin. These models generally assume that superspreaders will always agree to be vaccinated. Hence, they cannot capture unintended consequences such as policy resistance, where the behavioral response induced by a new vaccine policy tends to reduce the expected benefits of the policy. Here, we couple a model of influenza transmission on an empirically-based contact network with a psychologically structured model of influenza vaccinating behavior, where individual vaccinating decisions depend on social learning and past experiences of perceived infections, vaccine complications and vaccine failures. We find that policy resistance almost completely undermines the effectiveness of superspreader strategies: the most commonly explored approaches that target a randomly chosen neighbor of an individual, or that preferentially choose neighbors with many contacts, provide at best a 2% relative improvement over their non-targeted counterpart as compared to 12% when behavioral feedbacks are ignored. Increased vaccine coverage in super spreaders is offset by decreased coverage in non-superspreaders, and superspreaders also have a higher rate of perceived vaccine failures on account of being infected more often. Including incentives for vaccination provides modest improvements in outcomes. We conclude that the design of influenza vaccine strategies involving widespread incentive use and/or targeting of superspreaders should account for policy resistance, and mitigate it whenever possible.

How Can Vaccines Contribute to Solving the Antimicrobial Resistance Problem?

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Marc Lipsitch

2016-06-01

Full Text Available There is a growing appreciation for the role of vaccines in confronting the problem of antimicrobial resistance (AMR. Vaccines can reduce the prevalence of resistance by reducing the need for antimicrobial use and can reduce its impact by reducing the total number of cases. By reducing the number of pathogens that may be responsible for a particular clinical syndrome, vaccines can permit the use of narrower-spectrum antibiotics for empirical therapy. These effects may be amplified by herd immunity, extending protection to unvaccinated persons in the population. Because much selection for resistance is due to selection on bystander members of the normal flora, vaccination can reduce pressure for resistance even in pathogens not included in the vaccine. Some vaccines have had disproportionate effects on drug-resistant lineages within the target species, a benefit that could be more deliberately exploited in vaccine design. We describe the effects of current vaccines in controlling AMR, survey some vaccines in development with the potential to do so further, and discuss strategies to amplify these benefits. We conclude with a discussion of research and policy priorities to more fully enlist vaccines in the battle against AMR.

Potential use of [gammadelta] T cell-based vaccines in cancer immunotherapy

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Mohd Wajid A. Khan

2014-10-01

Full Text Available Immunotherapy is a fast advancing methodology involving one of two approaches: 1 compounds targeting immune checkpoints, and 2 cellular immunomodulators. The latter approach is still largely experimental and features in vitro generated, live immune effector cells or antigen-presenting cells (APC. [gammadelta] T cells are known for their efficient in vitro tumor killing activities. Consequently, many laboratories worldwide are currently testing the tumor killing function of [gammadelta] T cells in clinical trials. Reported benefits are modest; however, these studies have demonstrated that large [gammadelta] T cell infusions were well tolerated. Here, we discuss the potential of using human [gammadelta] T cells not as effector cells but as a novel cellular vaccine for treatment of cancer patients. Antigen-presenting [gammadelta] T cells do not require to home to tumor tissues but, instead, need to interact with endogenous, tumor-specific [alphabeta] T cells in secondary lymphoid tissues. Newly mobilised effector [alphabeta] T cells are then thought to overcome the immune blockade by creating proinflammatory conditions fit for effector T cell homing to and killing of tumor cells. Immunotherapy may include tumor antigen-loaded [gammadelta] T cells alone or in combination with immune checkpoint inhibitors.

Peptide Vaccine: Progress and Challenges

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Weidang Li

2014-07-01

Full Text Available Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

[Vaccine against human papilloma virus].

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Juárez-Albarrán, Alfredo César; Juárez-Gámez, Carlos Alberto

2008-01-01

Genital human papilloma virus infection (HPV) is the most common sexually transmitted infection worldwide, it is the cause of genital warts, and it is related with cervical cancer, the second most common cause of death from cancer in women in America, and the first in underdeveloped countries, and it is related with penis and prostate cancer in males also, and with anal cancer in both genders. This review examines the most important actual facts about HPV infection, and the new prophylactic vaccines. Two versions of the vaccine had been developed, both target HPV 16 and HPV 18, which involve approximately 70% of cervical cancer. One of them also targets HPV 6 and HPV 11, which account for approximately 90% of external genital warts. Both vaccines have an excellent safety profile, are highly immunogenic, and have atributed complete type specific protection against persistent infection and associated lesions in fully vaccinated girls and young women. The role of men as carriers of HPV as well as vectors for transmission is well documented. Several clinical trials are currently under way to determine the efficacy of vaccinating men. Reducing the cost of vaccination would be a priority for the developing world in order to get a broad target in poor countries.

Targeting the genital tract mucosa with a lipopeptide/recombinant adenovirus prime/boost vaccine induces potent and long-lasting CD8+ T cell immunity against herpes: importance of MyD88.

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Zhang, Xiuli; Dervillez, Xavier; Chentoufi, Aziz Alami; Badakhshan, Tina; Bettahi, Ilham; Benmohamed, Lbachir

2012-11-01

Targeting of the mucosal immune system of the genital tract with subunit vaccines has failed to induce potent and durable local CD8(+) T cell immunity, which is crucial for protection against many sexually transmitted viral pathogens, including HSV type 2 (HSV-2), which causes genital herpes. In this study, we aimed to investigate the potential of a novel lipopeptide/adenovirus type 5 (Lipo/rAdv5) prime/boost mucosal vaccine for induction of CD8(+) T cell immunity to protect the female genital tract from herpes. The lipopeptide vaccine and the rAdv5 vaccine express the immunodominant HSV-2 CD8(+) T cell epitope (gB(498-505)), and both were delivered intravaginally in the progesterone-induced B6 mouse model of genital herpes. Compared with mice immunized with the homologous lipopeptide/lipopeptide (Lipo/Lipo) vaccine, the Lipo/rAdv5 prime/boost immunized mice 1) developed potent and sustained HSV-specific CD8(+) T cells, detected in both the genital tract draining nodes and in the vaginal mucosa; 2) had significantly lower virus titers; 3) had decreased overt signs of genital herpes disease; and 4) did not succumb to lethal infection (p herpes infection and disease.

Use of Rhodamine B as a biomarker for oral plague vaccination of prairie dogs

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Fernandez, Julia Rodriguez-Ramos; Rocke, Tonie E.

2011-01-01

Oral vaccination against Yersinia pestis could provide a feasible approach for controlling plague in prairie dogs (Cynomys spp.) for conservation and public health purposes. Biomarkers are useful in wildlife vaccination programs to demonstrate exposure to vaccine baits. Rhodamine B (RB) was tested as a potential biomarker for oral plague vaccination because it allows nonlethal sampling of animals through hair, blood, and feces. We found that RB is an appropriate marker for bait uptake studies of C. ludovicianus) when used at concentrations 10 mg RB per kg target animal mass. Whiskers with follicles provided the best sample for RB detection.

Advanced Vaccine Candidates for Lassa Fever

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Igor S. Lukashevich

2012-10-01

Full Text Available Lassa virus (LASV is the most prominent human pathogen of the Arenaviridae. The virus is transmitted to humans by a rodent reservoir, Mastomys natalensis, and is capable of causing lethal Lassa Fever (LF. LASV has the highest human impact of any of the viral hemorrhagic fevers (with the exception of Dengue Fever with an estimated several hundred thousand infections annually, resulting in thousands of deaths in Western Africa. The sizeable disease burden, numerous imported cases of LF in non-endemic countries, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Presently there is no licensed vaccine against LF or approved treatment. Recently, several promising vaccine candidates have been developed which can potentially target different groups at risk. The purpose of this manuscript is to review the LASV pathogenesis and immune mechanisms involved in protection. The current status of pre-clinical development of the advanced vaccine candidates that have been tested in non-human primates will be discussed. Major scientific, manufacturing, and regulatory challenges will also be considered.

Chimeric L2-Based Virus-Like Particle (VLP Vaccines Targeting Cutaneous Human Papillomaviruses (HPV.

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Bettina Huber

Full Text Available Common cutaneous human papillomavirus (HPV types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas, but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa 17-36 on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross- protected against beta HPV5/20/24/38/96/16 (but not type 76, while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target

Self-Amplifying Replicon RNA Vaccine Delivery to Dendritic Cells by Synthetic Nanoparticles

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Kenneth C. McCullough

2014-10-01

Full Text Available Dendritic cells (DC play essential roles determining efficacy of vaccine delivery with respect to immune defence development and regulation. This renders DCs important targets for vaccine delivery, particularly RNA vaccines. While delivery of interfering RNA oligonucleotides to the appropriate intracellular sites for RNA-interference has proven successful, the methodologies are identical for RNA vaccines, which require delivery to RNA translation sites. Delivery of mRNA has benefitted from application of cationic entities; these offer value following endocytosis of RNA, when cationic or amphipathic properties can promote endocytic vesicle membrane perturbation to facilitate cytosolic translocation. The present review presents how such advances are being applied to the delivery of a new form of RNA vaccine, replicons (RepRNA carrying inserted foreign genes of interest encoding vaccine antigens. Approaches have been developed for delivery to DCs, leading to the translation of the RepRNA and encoded vaccine antigens both in vitro and in vivo. Potential mechanisms favouring efficient delivery leading to translation are discussed with respect to the DC endocytic machinery, showing the importance of cytosolic translocation from acidifying endocytic structures. The review relates the DC endocytic pathways to immune response induction, and the potential advantages for these self-replicating RNA vaccines in the near future.

Case-control vaccine effectiveness studies: Preparation, design, and enrollment of cases and controls.

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Verani, Jennifer R; Baqui, Abdullah H; Broome, Claire V; Cherian, Thomas; Cohen, Cheryl; Farrar, Jennifer L; Feikin, Daniel R; Groome, Michelle J; Hajjeh, Rana A; Johnson, Hope L; Madhi, Shabir A; Mulholland, Kim; O'Brien, Katherine L; Parashar, Umesh D; Patel, Manish M; Rodrigues, Laura C; Santosham, Mathuram; Scott, J Anthony; Smith, Peter G; Sommerfelt, Halvor; Tate, Jacqueline E; Victor, J Chris; Whitney, Cynthia G; Zaidi, Anita K; Zell, Elizabeth R

2017-06-05

Case-control studies are commonly used to evaluate effectiveness of licensed vaccines after deployment in public health programs. Such studies can provide policy-relevant data on vaccine performance under 'real world' conditions, contributing to the evidence base to support and sustain introduction of new vaccines. However, case-control studies do not measure the impact of vaccine introduction on disease at a population level, and are subject to bias and confounding, which may lead to inaccurate results that can misinform policy decisions. In 2012, a group of experts met to review recent experience with case-control studies evaluating the effectiveness of several vaccines; here we summarize the recommendations of that group regarding best practices for planning, design and enrollment of cases and controls. Rigorous planning and preparation should focus on understanding the study context including healthcare-seeking and vaccination practices. Case-control vaccine effectiveness studies are best carried out soon after vaccine introduction because high coverage creates strong potential for confounding. Endpoints specific to the vaccine target are preferable to non-specific clinical syndromes since the proportion of non-specific outcomes preventable through vaccination may vary over time and place, leading to potentially confusing results. Controls should be representative of the source population from which cases arise, and are generally recruited from the community or health facilities where cases are enrolled. Matching of controls to cases for potential confounding factors is commonly used, although should be reserved for a limited number of key variables believed to be linked to both vaccination and disease. Case-control vaccine effectiveness studies can provide information useful to guide policy decisions and vaccine development, however rigorous preparation and design is essential. Published by Elsevier Ltd.

Modeling the impact of rubella vaccination in Vietnam.

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Vynnycky, Emilia; Yoshida, Lay Myint; Huyen, Dang Thi Thanh; Trung, Nguyen Dac; Toda, Kohei; Cuong, Nguyen Van; Thi Hong, Duong; Ariyoshi, Koya; Miyakawa, Masami; Moriuchi, Hiroyuki; Tho, Le Huu; Nguyen, Hien Anh; Duc Anh, Dang; Jit, Mark; Hien, Nguyen Tran

2016-01-01

Supported by GAVI Alliance, measles-rubella vaccination was introduced in Vietnam in 2014, involving a mass campaign among 1-14 year olds and routine immunization of children aged 9 months. We explore the impact on the incidence of Congenital Rubella Syndrome (CRS) during 2013-2050 of this strategy and variants involving women aged 15-35 years. We use an age and sex-structured dynamic transmission model, set up using recently-collected seroprevalence data from Central Vietnam, and also consider different levels of transmission and contact patterns. If the serological profile resembles that in Central Vietnam, the planned vaccination strategy could potentially prevent 125,000 CRS cases by 2050 in Vietnam, despite outbreaks predicted in the meantime. Targeting the initial campaign at 15-35 year old women with or without children aged 9 months-14 years led to sustained reductions in incidence, unless levels of ongoing transmission were medium-high before vaccination started. Assumptions about contact greatly influenced predictions if the initial campaign just targeted 15-35 year old women and/or levels of ongoing transmission were medium-high. Given increased interest in rubella vaccination, resulting from GAVI Alliance funding, the findings are relevant for many countries.

Epstein-Barr Virus as a Promising Immunotherapeutic Target for Nasopharyngeal Carcinoma Treatment

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Sin-Yeang Teow

2017-01-01

Full Text Available Epstein-Barr virus (EBV is a pathogen that infects more than 90% of global human population. EBV primarily targets B-lymphocytes and epithelial cells while some of them infect monocyte/macrophage, T-lymphocytes, and dendritic cells (DCs. EBV infection does not cause death by itself but the infection has been persistently associated with certain type of cancers such as nasopharyngeal carcinoma (NPC, Burkitt’s lymphoma (BL, and Hodgkin’s lymphoma (HL. Recent findings have shown promise on targeting EBV proteins for cancer therapy by immunotherapeutic approach. Some studies have also shown the success of adopting EBV-based therapeutic vaccines for the prevention of EBV-associated cancer particularly on NPC. In-depth investigations are in progress to refine the current therapeutic and vaccination strategies. In present review, we discuss the highly potential EBV targets for NPC immunotherapy and therapeutic vaccine development as well as addressing the underlying challenges in the process of bringing the therapy and vaccination from the bench to bedside.

The Capricious Nature of Bacterial Pathogens: Phasevarions and Vaccine Development

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Aimee Tan

2016-12-01

Full Text Available Infectious diseases are a leading cause of morbidity and mortality worldwide, and vaccines are one of the most successful and cost-effective tools for disease prevention. One of the key considerations for rational vaccine development is the selection of appropriate antigens. Antigens must induce a protective immune response, and this response should be directed to stably expressed antigens so the target microbe can always be recognized by the immune system. Antigens with variable expression, due to environmental signals or phase variation (i.e., high frequency, random switching of expression, are not ideal vaccine candidates because variable expression could lead to immune evasion. Phase variation is often mediated by the presence of highly mutagenic simple tandem DNA repeats, and genes containing such sequences can be easily identified, and their use discounted as vaccine antigens reconsidered. Recent research has identified phase variably expressed DNA methyltransferases that act as global epigenetic regulators. These phase variable regulons, known as phasevarions, are associated with altered virulence phenotypes and/or expression of vaccine candidates. As such, genes encoding candidate vaccine antigens that have no obvious mechanism of phase variation may be subject to indirect, epigenetic control as part of a phasevarion. Bioinformatic and experimental studies are required to elucidate the distribution and mechanism of action of these DNA methyltransferases, and most importantly, whether they mediate epigenetic regulation of potential and current vaccine candidates. This process is essential to define the stably expressed antigen target profile of bacterial pathogens and thereby facilitate efficient, rational selection of vaccine antigens.

Prolonging herd immunity to cholera via vaccination: Accounting for human mobility and waning vaccine effects.

Directory of Open Access Journals (Sweden)

Corey M Peak

2018-02-01

Full Text Available Oral cholera vaccination is an approach to preventing outbreaks in at-risk settings and controlling cholera in endemic settings. However, vaccine-derived herd immunity may be short-lived due to interactions between human mobility and imperfect or waning vaccine efficacy. As the supply and utilization of oral cholera vaccines grows, critical questions related to herd immunity are emerging, including: who should be targeted; when should revaccination be performed; and why have cholera outbreaks occurred in recently vaccinated populations?We use mathematical models to simulate routine and mass oral cholera vaccination in populations with varying degrees of migration, transmission intensity, and vaccine coverage. We show that migration and waning vaccine efficacy strongly influence the duration of herd immunity while birth and death rates have relatively minimal impacts. As compared to either periodic mass vaccination or routine vaccination alone, a community could be protected longer by a blended "Mass and Maintain" strategy. We show that vaccination may be best targeted at populations with intermediate degrees of mobility as compared to communities with very high or very low population turnover. Using a case study of an internally displaced person camp in South Sudan which underwent high-coverage mass vaccination in 2014 and 2015, we show that waning vaccine direct effects and high population turnover rendered the camp over 80% susceptible at the time of the cholera outbreak beginning in October 2016.Oral cholera vaccines can be powerful tools for quickly protecting a population for a period of time that depends critically on vaccine coverage, vaccine efficacy over time, and the rate of population turnover through human mobility. Due to waning herd immunity, epidemics in vaccinated communities are possible but become less likely through complementary interventions or data-driven revaccination strategies.

Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production.

Science.gov (United States)

Oyarzún, Patricio; Kobe, Bostjan

2016-03-03

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.

Monitoring what governments "give for" and "spend on" vaccine procurement: Vaccine Procurement Assistance and Vaccine Procurement Baseline.

Science.gov (United States)

Nelson, E A S; Bloom, David E; Mahoney, Richard T

2014-01-01

The Global Vaccine Action Plan will require, inter alia, the mobilization of financial resources from donors and national governments - both rich and poor. Vaccine Procurement Assistance (VPA) and Vaccine Procurement Baseline (VPB) are two metrics that could measure government performance and track resources in this arena. VPA is proposed as a new subcategory of Official Development Assistance (ODA) given for the procurement of vaccines and VPB is a previously suggested measure of the share of Gross Domestic Product (GDP) that governments spend on their own vaccine procurement. To determine realistic targets for VPA and VPB. Organization for Economic Co-Operation and Development (OECD) and World Bank data for 2009 were analyzed to determine the proportions of bilateral ODA from the 23 Development Assistance Committee (DAC) countries disbursed (as % of GDP in current US$) for infectious disease control. DAC country contributions to the GAVI Alliance for 2009 were assessed as a measure of multilateral donor support for vaccines and immunization programs. In 2009, total DAC bilateral ODA was 0.16% of global GDP and 0.25% of DAC GDP. As a percentage of GDP, Norway (0.013%) and United Kingdom (0.0085%) disbursed the greatest proportion of bilateral ODA for infectious disease control, and Norway (0.024%) and Canada (0.008%) made the greatest contributions to the GAVI Alliance. In 2009 0.02% of DAC GDP was US$7.61 billion and 0.02% of the GDP of the poorest 117 countries was US$2.88 billion. Adopting 0.02% GDP as minimum targets for both VPA and VPB is based on realistic estimates of what both developed and developing countries should spend, and can afford to spend, to jointly ensure procurement of vaccines recommended by national and global bodies. New OECD purpose codes are needed to specifically track ODA disbursed for a) vaccine procurement; and b) immunization programs.

New strategies to improve the efficacy of colorectal cancer vaccines: from bench to bedside.

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Mocellin, Simone

2006-12-01

By exploiting a naturally occurring defense system, anticancer vaccination embodies an ideal non-toxic treatment capable of evoking tumor-specific immune responses that can ultimately recognize and kill colorectal cancer (CRC) cells. Despite the enormous theoretical potential of active specific immunotherapy, no vaccination regimen has achieved sufficient therapeutic efficacy necessary for clinical implementation. Nevertheless, several immunological advances have opened new avenues of research to decipher the biological code governing tumor immune responsiveness, and this is leading to the design of potentially more effective immunotherapeutic protocols. This review briefly summarizes the principles behind anti-CRC vaccination and describes the most promising immunological strategies that have been developed, which are expected to renew interest in this molecularly targeted anticancer approach.

Swine influenza virus: zoonotic potential and vaccination strategies for the control of avian and swine influenzas.

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Thacker, Eileen; Janke, Bruce

2008-02-15

Influenza viruses are able to infect humans, swine, and avian species, and swine have long been considered a potential source of new influenza viruses that can infect humans. Swine have receptors to which both avian and mammalian influenza viruses bind, which increases the potential for viruses to exchange genetic sequences and produce new reassortant viruses in swine. A number of genetically diverse viruses are circulating in swine herds throughout the world and are a major cause of concern to the swine industry. Control of swine influenza is primarily through the vaccination of sows, to protect young pigs through maternally derived antibodies. However, influenza viruses continue to circulate in pigs after the decay of maternal antibodies, providing a continuing source of virus on a herd basis. Measures to control avian influenza in commercial poultry operations are dictated by the virulence of the virus. Detection of a highly pathogenic avian influenza (HPAI) virus results in immediate elimination of the flock. Low-pathogenic avian influenza viruses are controlled through vaccination, which is done primarily in turkey flocks. Maintenance of the current HPAI virus-free status of poultry in the United States is through constant surveillance of poultry flocks. Although current influenza vaccines for poultry and swine are inactivated and adjuvanted, ongoing research into the development of newer vaccines, such as DNA, live-virus, or vectored vaccines, is being done. Control of influenza virus infection in poultry and swine is critical to the reduction of potential cross-species adaptation and spread of influenza viruses, which will minimize the risk of animals being the source of the next pandemic.

Targeted Facebook Advertising is a Novel and Effective Method of Recruiting Participants into a Human Papillomavirus Vaccine Effectiveness Study

OpenAIRE

Subasinghe, Asvini K; Nguyen, Margaret; Wark, John D; Tabrizi, Sepehr N; Garland, Suzanne M

2016-01-01

Background Targeted advertising using social networking sites (SNS) as a recruitment strategy in health research is in its infancy. Objective The aim of this study was to determine the feasibility of targeted Facebook advertisements to increase recruitment of unvaccinated women into a human papillomavirus (HPV) vaccine effectiveness study. Methods Between September 2011 and November 2013, females aged 18 to 25 years, residing in Victoria, Australia, were recruited through Facebook advertiseme...

In "Step" with HIV Vaccines? A Content Analysis of Local Recruitment Campaigns for an International HIV Vaccine Study.

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Frew, Paula M; Macias, Wendy; Chan, Kayshin; Harding, Ashley C

2009-01-01

During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the "Step Study"). This study examined persuasive features consistent with the Elaboration Likelihood Model (ELM) including message content, personal relevance of HIV/AIDS and vaccine research, intended audiences, information sources, and other contextual features. The results indicated variation in messages and communication approaches with gay men more exclusively targeted in these regions. Racial/ethnic representations also differed by campaign. Most of the materials promote affective evaluation of the information through heuristic cueing. Implications for subsequent campaigns and research directions are discussed.

Schools as potential vaccination venue for vaccines outside regular EPI schedule: results from a school census in Pakistan

NARCIS (Netherlands)

Soofi, S.B.; Haq, I.U.; Khan, M.I.; Siddiqui, M.B.; Mirani, M.; Tahir, R.; Hussain, I.; Puri, M.K.; Suhag, Z.H.; Khowaja, A.R.; Lasi, A.R.; Clemens, J.D.; Favorov, M.; Ochiai, R.L.; Bhutta, Z.A.

2012-01-01

BACKGROUND: Vaccines are the most effective public health intervention. Expanded Program on Immunization (EPI) provides routine vaccination in developing countries. However, vaccines that cannot be given in EPI schedule such as typhoid fever vaccine need alternative venues. In areas where school

Comparative evaluation of the potential impact of rotavirus versus hpv vaccination in GAVI-eligible countries: A preliminary analysis focused on the relative disease burden

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Chang Joshua

2011-06-01

Full Text Available Abstract Background Immunization policymakers at global and local levels need to establish priorities among new vaccines competing for limited resources. However, comparison of the potential impact of single vaccination programs is challenging, primarily due to the limited number of vaccine analyses as well as their differing analytic approaches and reporting formats. The purpose of this study is to provide early insight into how the comparative impact of different new vaccines could be assessed in resource-poor settings with respect to affordability, cost-effectiveness, and distributional equity. Methods We compared the health, economic, and financial consequences of introducing the two vaccines in 72 GAVI-eligible countries using a number of different outcome measures to evaluate affordability, cost-effectiveness, and distributional equity. We use simple static models to standardize the analytic framework and improve comparability between the two new vaccines. These simple models were validated by leveraging previously developed, more complex models for rotavirus and human papillomavirus (HPV. Results With 70% coverage of a single-age cohort of infants and pre-adolescent girls, the lives saved with rotavirus (~274,000 and HPV vaccines (~286,000 are similar, although the timing of averted mortality differs; rotavirus-attributable deaths occur in close proximity to infection, while HPV-related cancer deaths occur largely after age 30. Deaths averted per 1000 vaccinated are 5.2 (rotavirus and 12.6 (HPV. Disability-adjusted life years (DALYs averted were ~7.15 million (rotavirus and ~1.30 million (HPV, reflecting the greater influence of discounting on the latter, given the lagtime between vaccination and averted cancer. In most countries (68 for rotavirus and 66 for HPV, at the cost of I$25 per vaccinated individual the incremental cost per DALY averted was lower than each country's GDP per capita. Financial resources required for vaccination

Comparative evaluation of the potential impact of rotavirus versus HPV vaccination in GAVI-eligible countries: a preliminary analysis focused on the relative disease burden.

Science.gov (United States)

Kim, Sun-Young; Sweet, Steven; Chang, Joshua; Goldie, Sue J

2011-06-16

Immunization policymakers at global and local levels need to establish priorities among new vaccines competing for limited resources. However, comparison of the potential impact of single vaccination programs is challenging, primarily due to the limited number of vaccine analyses as well as their differing analytic approaches and reporting formats. The purpose of this study is to provide early insight into how the comparative impact of different new vaccines could be assessed in resource-poor settings with respect to affordability, cost-effectiveness, and distributional equity. We compared the health, economic, and financial consequences of introducing the two vaccines in 72 GAVI-eligible countries using a number of different outcome measures to evaluate affordability, cost-effectiveness, and distributional equity. We use simple static models to standardize the analytic framework and improve comparability between the two new vaccines. These simple models were validated by leveraging previously developed, more complex models for rotavirus and human papillomavirus (HPV). With 70% coverage of a single-age cohort of infants and pre-adolescent girls, the lives saved with rotavirus (~274,000) and HPV vaccines (~286,000) are similar, although the timing of averted mortality differs; rotavirus-attributable deaths occur in close proximity to infection, while HPV-related cancer deaths occur largely after age 30. Deaths averted per 1000 vaccinated are 5.2 (rotavirus) and 12.6 (HPV). Disability-adjusted life years (DALYs) averted were ~7.15 million (rotavirus) and ~1.30 million (HPV), reflecting the greater influence of discounting on the latter, given the lagtime between vaccination and averted cancer. In most countries (68 for rotavirus and 66 for HPV, at the cost of I$25 per vaccinated individual) the incremental cost per DALY averted was lower than each country's GDP per capita. Financial resources required for vaccination with rotavirus are higher than with HPV since both

Smallpox vaccination and all-cause infectious disease hospitalization

DEFF Research Database (Denmark)

Sørup, Signe; Villumsen, Marie; Ravn, Henrik

2011-01-01

There is growing evidence from observational studies and randomized trials in low-income countries that vaccinations have non-specific effects. Administration of live vaccines reduces overall child morbidity and mortality, presumably due to protection against non-targeted infections. In Denmark, ......, the live vaccine against smallpox was phased out in the 1970s due to the eradication of smallpox. We used the phasing-out period to investigate the effect of smallpox vaccination on the risk of hospitalization for infections.......There is growing evidence from observational studies and randomized trials in low-income countries that vaccinations have non-specific effects. Administration of live vaccines reduces overall child morbidity and mortality, presumably due to protection against non-targeted infections. In Denmark...

Mumps vaccine associated orchitis: Evidence supporting a potential immune-mediated mechanism.

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Clifford, Vanessa; Wadsley, Jane; Jenner, Bernard; Buttery, Jim P

2010-03-19

We report 3 cases of orchitis following vaccination with mumps-measles-rubella (MMR) vaccine, two with an onset within 3 days following vaccination. Orchitis is a common complication of mumps infection, particularly in post-pubertal males, and is also recognized as a very rare complication of mumps vaccination. These cases, discussed together with a comprehensive review of the existing literature regarding post-vaccine orchitis, highlight uncertainty regarding the pathogenesis of post-vaccine orchitis. Copyright 2010 Elsevier Ltd. All rights reserved.

A recombinant multi-antigen vaccine with broad protection potential against avian pathogenic Escherichia coli.

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Angelica Van Goor

Full Text Available Chickens are a major source of protein worldwide, yet infectious diseases continue to threaten the poultry industry. Avian pathogenic Escherichia coli (APEC, a subgroup of extraintestinal pathogenic E. coli (ExPEC, causes colibacillosis in chickens resulting in economic loss because of treatment, condemnation of products, and death. In this study, we evaluated a recombinant antigens (rAg vaccine combining common ExPEC surface proteins EtsC, OmpA, OmpT, and TraT for broad protective potential against APEC infections in chickens. The specific objectives were to evaluate antibody (serum and cytokines (lymphoid organs responses to vaccination; in vitro bactericidal ability of serum and splenocytes against multiple APEC serotypes; and in vivo protection against APEC challenge in chickens. Groups of four-day old chickens (N = 10 were vaccinated twice (two-week interval subcutaneously with rAgs alone or in combination and CpG adjuvant or PBS (control. IgY antibody in the serum and mRNA expression of IL-1β, IL-6, IL-18, IFN-γ, IL-4, IFN-β, and IL-8 in bursa, spleen, and thymus were measured using ELISA and RT-qPCR, respectively. Serum and splenocytes were tested for their bactericidal ability in vitro against multiple APEC isolates. Vaccinated and non-vaccinated chickens were challenged with 108 CFU of APEC-O2 via air sac at 31 days post first vaccination. Vaccine protection was determined by the decrease of bacterial loads in blood and organs (lung, heart, spleen, and liver, as well as gross colibacillosis lesion scores in air sac, heart, and liver. Vaccination significantly (P < 0.05 elicited IgY against specific antigens, induced immune related mRNA expression in the spleen and bursa, reduced in vitro growth of multiple APEC serotypes, and decreased bacterial loads in the heart and spleen, and gross lesion scores of the air sac, heart and liver in chickens. The vaccine reported may be used to provide broad protection against APEC strains

Fc Receptor-Targeting of Immunogen as a Strategy for Enhanced Antigen Loading, Vaccination, and Protection Using Intranasally-Administered Antigen-Pulsed Dendritic Cells

Science.gov (United States)

Pham, Giang H.; Iglesias, Bibiana V.; Gosselin, Edmund J.

2014-01-01

Dendritic cells (DCs) play a critical role in the generation of adaptive immunity via the efficient capture, processing, and presentation of antigen (Ag) to naïve T cells. Administration of Ag-pulsed DCs is also an effective strategy for enhancing immunity to tumors and infectious disease organisms. Studies have also demonstrated that targeting Ags to Fcγ receptors (FcγR) on Ag presenting cells can enhance humoral and cellular immunity in vitro and in vivo. Specifically, our studies using an F. tularensis (Ft) infectious disease vaccine model have demonstrated that targeting immunogens to FcγR via intranasal (i.n.) administration of monoclonal antibody (mAb)-inactivated Ft (iFt) immune complexes (ICs) enhances protection against Ft challenge. Ft is the causative agent of tularemia, a debilitating disease of humans and other mammals and a category A biothreat agent for which there is no approved vaccine. Therefore, using iFt Ag as a model immunogen, we sought to determine if ex vivo targeting of iFt to FcγR on DCs would enhance the potency of i.n. administered iFt-pulsed DCs. In this study, bone marrow-derived DCs (BMDCs) were pulsed ex vivo with iFt or mAb-iFt ICs. Intranasal administration of mAb-iFt-pulsed BMDCs enhanced humoral and cellular immune responses, as well as protection against Ft live vaccine strain (LVS) challenge. Increased protection correlated with increased iFt loading on the BMDC surface as a consequence of FcγR targeting. However, the inhibitory FcγRIIB had no impact on this enhancement. In conclusion, targeting Ag ex vivo to FcγR on DCs provides a method for enhanced Ag loading of DCs ex vivo, thereby reducing the amount of Ag required, while also avoiding the inhibitory impact of FcγRIIB. Thus, this represents a simple and less invasive strategy for increasing the potency of ex vivo-pulsed DC vaccines against chronic infectious diseases and cancer. PMID:25068496

Fc receptor-targeting of immunogen as a strategy for enhanced antigen loading, vaccination, and protection using intranasally administered antigen-pulsed dendritic cells.

Science.gov (United States)

Pham, Giang H; Iglesias, Bibiana V; Gosselin, Edmund J

2014-09-08

Dendritic cells (DCs) play a critical role in the generation of adaptive immunity via the efficient capture, processing, and presentation of antigen (Ag) to naïve T cells. Administration of Ag-pulsed DCs is also an effective strategy for enhancing immunity to tumors and infectious disease organisms. Studies have also demonstrated that targeting Ags to Fcγ receptors (FcγR) on Ag presenting cells can enhance humoral and cellular immunity in vitro and in vivo. Specifically, our studies using a Francisella tularensis (Ft) infectious disease vaccine model have demonstrated that targeting immunogens to FcγR via intranasal (i.n.) administration of monoclonal antibody (mAb)-inactivated Ft (iFt) immune complexes (ICs) enhances protection against Ft challenge. Ft is the causative agent of tularemia, a debilitating disease of humans and other mammals and a category A biothreat agent for which there is no approved vaccine. Therefore, using iFt Ag as a model immunogen, we sought to determine if ex vivo targeting of iFt to FcγR on DCs would enhance the potency of i.n. administered iFt-pulsed DCs. In this study, bone marrow-derived DCs (BMDCs) were pulsed ex vivo with iFt or mAb-iFt ICs. Intranasal administration of mAb-iFt-pulsed BMDCs enhanced humoral and cellular immune responses, as well as protection against Ft live vaccine strain (LVS) challenge. Increased protection correlated with increased iFt loading on the BMDC surface as a consequence of FcγR-targeting. However, the inhibitory FcγRIIB had no impact on this enhancement. In conclusion, targeting Ag ex vivo to FcγR on DCs provides a method for enhanced Ag loading of DCs ex vivo, thereby reducing the amount of Ag required, while also avoiding the inhibitory impact of FcγRIIB. Thus, this represents a simple and less invasive strategy for increasing the potency of ex vivo-pulsed DC vaccines against chronic infectious diseases and cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Vaccines for bovine neosporosis: current status and key aspects for development.

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Horcajo, P; Regidor-Cerrillo, J; Aguado-Martínez, A; Hemphill, A; Ortega-Mora, L M

2016-12-01

Bovine neosporosis is a worldwide concern due to its global distribution and great economic impact. Reproductive failure in cattle due to abortion leads to major economic losses associated with the disease. Currently, there is no treatment or vaccine available against abortion or transmission caused by Neospora caninum infection in cattle. However, vaccination is considered the best measure of control against bovine neosporosis. Several host and parasite factors can influence the dynamics of the infection in bovines. Moreover, the availability of well-defined infection models is a key factor for the evaluation of vaccine candidates. However, working with cattle is not easy due to difficult handling, facilities and costs, and therefore, 'more affordable' models could be used for screening of promising vaccines to establish proof of concept. So far, live-attenuated vaccines have shown good efficacy against exogenous transplacental transmission; however, they have relevant disadvantages and associated risks, which render inactivated or subunit vaccines the best way forward. The identification of novel potential targets and vaccines, and the application of innovative vaccine technologies in harmonized experimental animal models, will accelerate the development of an effective vaccine against bovine neosporosis. © 2016 John Wiley & Sons Ltd.

'Hesitant compliers': Qualitative analysis of concerned fully-vaccinating parents.

Science.gov (United States)

Enkel, Stephanie L; Attwell, Katie; Snelling, Thomas L; Christian, Hayley E

2017-10-11

Some parents are hesitant about vaccines and yet still vaccinate their children. Vaccine behaviours are not fixed and parents who are concerned but nonetheless adherent to standard schedules could switch to an unconventional schedule, delaying or cherry-picking vaccines. There is a need to better understand vaccine hesitancy in specific contexts, acknowledging cultural and geographical variation, to ensure interventions targeting hesitancy are well directed and received. To identify the behaviours, knowledge and attitudes of 'hesitant compliers' in Perth, Western Australia, nine one-on-one in-depth interviews were conducted with vaccinating parents of children (vaccination as important for themselves and their community, despite their limited knowledge of vaccine preventable diseases. Parents reported concerns about potential side effects, and worried about the safety of the measles-mumps-rubella (MMR) and seasonal influenza vaccines. Concerned about the role of anti-vaccination information in the community, some sought to isolate themselves from parents who did not vaccinate, although others were concerned that this could entrench non-vaccinators' behaviours. Parents' views were all underlaid by two pivotal 'vaccine-related events' that had occurred in the community: the severe injury of a baby from seasonal influenza vaccination in 2010, and the death of a baby from whooping cough in 2015. Parents interpreted pivotal vaccine-related events in the community as requiring them to take personal responsibility for vaccine decisions. Their reports of continued vaccine fears (evident in international studies in recent decades) demonstrate that vaccine scares have long lasting effects. With vaccine rates high and stable, current strategies appear to be have little impact on addressing parental vaccine concerns. Further research is required to determine the prevalence of hesitancy amongst vaccinating parents and identify critical points for intervention. Copyright © 2017

Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

Science.gov (United States)

Payne, Richard; McDonald, David; Byrne, Scott

2015-10-01

Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

Bringing influenza vaccines into the 21st century.

Science.gov (United States)

Settembre, Ethan C; Dormitzer, Philip R; Rappuoli, Rino

2014-01-01

The recent H7N9 influenza outbreak in China highlights the need for influenza vaccine production systems that are robust and can quickly generate substantial quantities of vaccines that target new strains for pandemic and seasonal immunization. Although the influenza vaccine system, a public-private partnership, has been effective in providing vaccines, there are areas for improvement. Technological advances such as mammalian cell culture production and synthetic vaccine seeds provide a means to increase the speed and accuracy of targeting new influenza strains with mass-produced vaccines by dispensing with the need for egg isolation, adaptation, and reassortment of vaccine viruses. New influenza potency assays that no longer require the time-consuming step of generating sheep antisera could further speed vaccine release. Adjuvants that increase the breadth of the elicited immune response and allow dose sparing provide an additional means to increase the number of available vaccine doses. Together these technologies can improve the influenza vaccination system in the near term. In the longer term, disruptive technologies, such as RNA-based flu vaccines and 'universal' flu vaccines, offer a promise of a dramatically improved influenza vaccine system.

Neurologic complications of vaccinations.

Science.gov (United States)

Miravalle, Augusto A; Schreiner, Teri

2014-01-01

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.

Rotavirus vaccines

Science.gov (United States)

Yen, Catherine; Tate, Jacqueline E; Hyde, Terri B; Cortese, Margaret M; Lopman, Benjamin A; Jiang, Baoming; Glass, Roger I; Parashar, Umesh D

2014-01-01

Rotavirus is the leading cause of severe diarrhea among children rotavirus vaccines have been efficacious and effective, with many countries reporting substantial declines in diarrheal and rotavirus-specific morbidity and mortality. However, the full public health impact of these vaccines has not been realized. Most countries, including those with the highest disease burden, have not yet introduced rotavirus vaccines into their national immunization programs. Research activities that may help inform vaccine introduction decisions include (1) establishing effectiveness, impact, and safety for rotavirus vaccines in low-income settings; (2) identifying potential strategies to improve performance of oral rotavirus vaccines in developing countries, such as zinc supplementation; and (3) pursuing alternate approaches to oral vaccines, such as parenteral immunization. Policy- and program-level barriers, such as financial implications of new vaccine introductions, should be addressed to ensure that countries are able to make informed decisions regarding rotavirus vaccine introduction. PMID:24755452

Harnessing Invariant NKT Cells to Improve Influenza Vaccines: A Pig Perspective

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Guan Yang

2017-12-01

Full Text Available Invariant natural killer T (iNKT cells are an “innate-like” T cell lineage that recognize glycolipid rather than peptide antigens by their semi-invariant T cell receptors. Because iNKT cells can stimulate an extensive array of immune responses, there is considerable interest in targeting these cells to enhance human vaccines against a wide range of microbial pathogens. However, long overlooked is the potential to harness iNKT cell antigens as vaccine adjuvants for domestic animal species that express the iNKT cell–CD1d system. In this review, we discuss the prospect of targeting porcine iNKT cells as a strategy to enhance the efficiency of swine influenza vaccines. In addition, we compare the phenotype and tissue distribution of porcine iNKT cells. Finally, we discuss the challenges that must be overcome before iNKT cell agonists can be contemplated for veterinary use in livestock.

Viral booster vaccines improve Mycobacterium bovis BCG-induced protection against bovine tuberculosis.

Science.gov (United States)

Vordermeier, H Martin; Villarreal-Ramos, Bernardo; Cockle, Paul J; McAulay, Martin; Rhodes, Shelley G; Thacker, Tyler; Gilbert, Sarah C; McShane, Helen; Hill, Adrian V S; Xing, Zhou; Hewinson, R Glyn

2009-08-01

Previous work with small-animal laboratory models of tuberculosis has shown that vaccination strategies based on heterologous prime-boost protocols using Mycobacterium bovis bacillus Calmette-Guérin (BCG) to prime and modified vaccinia virus Ankara strain (MVA85A) or recombinant attenuated adenoviruses (Ad85A) expressing the mycobacterial antigen Ag85A to boost may increase the protective efficacy of BCG. Here we report the first efficacy data on using these vaccines in cattle, a natural target species of tuberculous infection. Protection was determined by measuring development of disease as an end point after M. bovis challenge. Either Ad85A or MVA85A boosting resulted in protection superior to that given by BCG alone: boosting BCG with MVA85A or Ad85A induced significant reduction in pathology in four/eight parameters assessed, while BCG vaccination alone did so in only one parameter studied. Protection was particularly evident in the lungs of vaccinated animals (median lung scores for naïve and BCG-, BCG/MVA85A-, and BCG/Ad85A-vaccinated animals were 10.5, 5, 2.5, and 0, respectively). The bacterial loads in lymph node tissues were also reduced after viral boosting of BCG-vaccinated calves compared to those in BCG-only-vaccinated animals. Analysis of vaccine-induced immunity identified memory responses measured by cultured enzyme-linked immunospot assay as well as in vitro interleukin-17 production as predictors of vaccination success, as both responses, measured before challenge, correlated positively with the degree of protection. Therefore, this study provides evidence of improved protection against tuberculosis by viral booster vaccination in a natural target species and has prioritized potential correlates of vaccine efficacy for further evaluation. These findings also have implications for human tuberculosis vaccine development.

Is an HIV vaccine possible?

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Nancy A. Wilson

Full Text Available The road to the discovery of a vaccine for HIV has been arduous and will continue to be difficult over the ensuing twenty years. Most vaccines are developed by inducing neutralizing antibodies against the target pathogen or by using attenuated strains of the particular pathogen to engender a variety of protective immune responses. Unfortunately, simple methods of generating anti-HIV antibodies have already failed in a phase III clinical trial. While attenuated SIV variants work well against homologous challenges in non-human primates, the potential for reversion to a more pathogenic virus and recombination with challenge viruses will preclude the use of attenuated HIV in the field. It has been exceedingly frustrating to vaccinate for HIV-specific neutralizing antibodies given the enormous diversity of the Envelope (Env glycoprotein and its well-developed glycan shield. However, there are several antibodies that will neutralize many different strains of HIV and inducing these types of antibodies in vaccinees remains the goal of a vigorous effort to develop a vaccine for HIV based on neutralizing antibodies. Given the difficulty in generating broadly reactive neutralizing antibodies, the HIV vaccine field has turned its attention to inducing T cell responses against the virus using a variety of vectors. Unfortunately, the results from Merck's phase IIb STEP trial proved to be disappointing. Vaccinees received Adenovirus type 5 (Ad5 expressing Gag, Pol, and Nef of HIV. This vaccine regimen failed to either prevent infection or reduce the level of HIV replication after challenge. These results mirrored those in non-human primate testing of Ad5 using rigorous SIV challenge models. This review will focus on recent developments in HIV vaccine development. We will deal largely with attempts to develop a T cell-based vaccine using the non-human primate SIV challenge model.

Potential Cost-Effectiveness of RSV Vaccination of Infants and Pregnant Women in Turkey: An Illustration Based on Bursa Data.

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Koen B Pouwels

Full Text Available Worldwide, respiratory syncytial virus (RSV is considered to be the most important viral cause of respiratory morbidity and mortality among infants and young children. Although no active vaccine is available on the market yet, there are several active vaccine development programs in various stages. To assess whether one of these vaccines might be a future asset for national immunization programs, modeling the costs and benefits of various vaccination strategies is needed.To evaluate the potential cost-effectiveness of RSV vaccination of infants and/or pregnant women in Turkey.A multi-cohort static Markov model with cycles of one month was used to compare the cost-effectiveness of vaccinated cohorts versus non-vaccinated cohorts. The 2014 Turkish birth cohort was divided by twelve to construct twelve monthly birth cohorts of equal size (111,459 new-borns. Model input was based on clinical data from a multicenter prospective study from Bursa, Turkey, combined with figures from the (international literature and publicly available data from the Turkish Statistical Institute (TÜÏK. Incremental cost-effectiveness ratios (ICERs were expressed in Turkish Lira (TL per quality-adjusted life year (QALY gained.Vaccinating infants at 2 and 4 months of age would prevent 145,802 GP visits, 8,201 hospitalizations and 48 deaths during the first year of life, corresponding to a total gain of 1650 QALYs. The discounted ICER was estimated at 51,969 TL (26,220 US $ in 2013 per QALY gained. Vaccinating both pregnant women and infants would prevent more cases, but was less attractive from a pure economic point of view with a discounted ICER of 61,653 TL (31,106 US $ in 2013 per QALY. Vaccinating only during pregnancy would result in fewer cases prevented than infant vaccination and a less favorable ICER.RSV vaccination of infants and/or pregnant women has the potential to be cost-effective in Turkey. Although using relatively conservative assumptions, all evaluated

Systems integration of biodefense omics data for analysis of pathogen-host interactions and identification of potential targets.

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Peter B McGarvey

2009-09-01

Full Text Available The NIAID (National Institute for Allergy and Infectious Diseases Biodefense Proteomics program aims to identify targets for potential vaccines, therapeutics, and diagnostics for agents of concern in bioterrorism, including bacterial, parasitic, and viral pathogens. The program includes seven Proteomics Research Centers, generating diverse types of pathogen-host data, including mass spectrometry, microarray transcriptional profiles, protein interactions, protein structures and biological reagents. The Biodefense Resource Center (www.proteomicsresource.org has developed a bioinformatics framework, employing a protein-centric approach to integrate and support mining and analysis of the large and heterogeneous data. Underlying this approach is a data warehouse with comprehensive protein + gene identifier and name mappings and annotations extracted from over 100 molecular databases. Value-added annotations are provided for key proteins from experimental findings using controlled vocabulary. The availability of pathogen and host omics data in an integrated framework allows global analysis of the data and comparisons across different experiments and organisms, as illustrated in several case studies presented here. (1 The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells infected by different bacterial (Bacillus anthracis and Salmonella typhimurium and viral (orthopox pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. (2 The analysis of a vaccinia-human protein interaction network supplemented with protein accumulation levels led to the identification of human Keratin, type II cytoskeletal 4 protein as a potential therapeutic target. (3 Comparison of complete genomes from pathogenic variants coupled with experimental information on complete proteomes allowed the identification and

Targeted Delivery of Toxoplasma gondii Antigens to Dendritic Cells Promote Immunogenicity and Protective Efficiency against Toxoplasmosis

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Zineb Lakhrif

2018-02-01

Full Text Available Toxoplasmosis is a major public health problem and the development of a human vaccine is of high priority. Efficient vaccination against Toxoplasma gondii requires both a mucosal and systemic Th1 immune response. Moreover, dendritic cells play a critical role in orchestrating the innate immune functions and driving specific adaptive immunity to T. gondii. In this study, we explore an original vaccination strategy that combines administration via mucosal and systemic routes of fusion proteins able to target the major T. gondii surface antigen SAG1 to DCs using an antibody fragment single-chain fragment variable (scFv directed against DEC205 endocytic receptor. Our results show that SAG1 targeting to DCs by scFv via intranasal and subcutaneous administration improved protection against chronic T. gondii infection. A marked reduction in brain parasite burden is observed when compared with the intranasal or the subcutaneous route alone. DC targeting improved both local and systemic humoral and cellular immune responses and potentiated more specifically the Th1 response profile by more efficient production of IFN-γ, interleukin-2, IgG2a, and nasal IgA. This study provides evidence of the potential of DC targeting for the development of new vaccines against a range of Apicomplexa parasites.

Cysteine proteases as potential antigens in antiparasitic DNA vaccines

DEFF Research Database (Denmark)

Jørgensen, Louise von Gersdorff; Buchmann, Kurt

2011-01-01

En litteraturgennemgang af muligheder for at bruge cystein proteaser som antigener i antiparasitære vacciner.......En litteraturgennemgang af muligheder for at bruge cystein proteaser som antigener i antiparasitære vacciner....

Extracellular vesicles from parasitic helminths and their potential utility as vaccines.

Science.gov (United States)

Mekonnen, Gebeyaw Getnet; Pearson, Mark; Loukas, Alex; Sotillo, Javier

2018-03-01

Helminths are multicellular parasites affecting nearly three billion people worldwide. To orchestrate a parasitic existence, helminths secrete different molecules, either in soluble form or contained within extracellular vesicles (EVs). EVs are secreted by most cell types and organisms, and have varied roles in intercellular communication, including immune modulation and pathogenesis. Areas covered: In this review, we describe the nucleic acid and proteomic composition of EVs from helminths, with a focus on the protein vaccine candidates present on the EV surface membrane, and discuss the potential utility of helminth EVs and their constituent proteins in the fight against helminth infections. Expert commentary: A significant number of proteins present in helminth-secreted EVs are known vaccine candidates. The characterization of helminth EV proteomes will shed light on host-pathogen interactions, facilitate the discovery of new diagnostic biomarkers, and provide a novel approach for the development of new control measures against helminth infections.

Non-invasive monitoring of Streptococcus pyogenes vaccine efficacy using biophotonic imaging.

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Faraz M Alam

Full Text Available Streptococcus pyogenes infection of the nasopharynx represents a key step in the pathogenic cycle of this organism and a major focus for vaccine development, requiring robust models to facilitate the screening of potentially protective antigens. One antigen that may be an important target for vaccination is the chemokine protease, SpyCEP, which is cell surface-associated and plays a role in pathogenesis. Biophotonic imaging (BPI can non-invasively characterize the spatial location and abundance of bioluminescent bacteria in vivo. We have developed a bioluminescent derivative of a pharyngeal S. pyogenes strain by transformation of an emm75 clinical isolate with the luxABCDE operon. Evaluation of isogenic recombinant strains in vitro and in vivo confirmed that bioluminescence conferred a growth deficit that manifests as a fitness cost during infection. Notwithstanding this, bioluminescence expression permitted non-invasive longitudinal quantitation of S. pyogenes within the murine nasopharynx albeit with a detection limit corresponding to approximately 10(5 bacterial colony forming units (CFU in this region. Vaccination of mice with heat killed streptococci, or with SpyCEP led to a specific IgG response in the serum. BPI demonstrated that both vaccine candidates reduced S. pyogenes bioluminescence emission over the course of nasopharyngeal infection. The work suggests the potential for BPI to be used in the non-invasive longitudinal evaluation of potential S. pyogenes vaccines.

Vaccination with human papillomavirus pseudovirus-encapsidated plasmids targeted to skin using microneedles.

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Rhonda C Kines

Full Text Available Human papilloma virus-like particles (HPV VLP serve as the basis of the current licensed vaccines for HPV. We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from respiratory syncytial virus (RSV in HPV pseudovirions (PsV is immunogenic when delivered intravaginally. Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. In this study we asked: 1 whether HPV16 VLP administered by microneedles could induce protective immune responses to HPV16 and 2 whether HPV16 PsV-encapsidated plasmids delivered by microneedles could elicit immune responses to both HPV and the antigen delivered by the transgene. Mice immunized with HPV16 VLP coated microneedles generated robust neutralizing antibody responses and were protected from HPV16 challenge. Microneedle arrays coated with HPV16-M/M2 or HPV16-F protein (genes of RSV were then tested and dose-dependent HPV and F-specific antibody responses were detected post-immunization, and M/M2-specific T-cell responses were detected post RSV challenge, respectively. HPV16 PsV-F immunized mice were fully protected from challenge with HPV16 PsV and had reduced RSV viral load in lung and nose upon intranasal RSV challenge. In summary, HPV16 PsV-encapsidated DNA delivered by microneedles induced neutralizing antibody responses against HPV and primed for antibody and T-cell responses to RSV antigens encoded by the encapsidated plasmids. Although the immunogenicity of the DNA component was just above the dose response threshold, the HPV-specific immunity was robust. Taken together, these data suggest microneedle delivery of lyophilized HPV PsV could provide a practical, thermostable combined vaccine approach that could be developed for clinical evaluation.

Uptake of the human papillomavirus-vaccination within the free-of-charge childhood vaccination programme in Denmark.

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Widgren, Katarina; Simonsen, Jacob; Valentiner-Branth, Palle; Mølbak, Kåre

2011-12-06

Persistent infection with human papillomavirus (HPV) is a prerequisite for cervical cancer, which causes 175 yearly deaths and substantial morbidity in Denmark. In January 2009, HPV-vaccination for 12 year-old girls was introduced into the free-of-charge childhood vaccination programme. Due to concerns about potential poor compliance we determined the uptake and identified determinants for vaccination after the first year of the programme. All vaccinations given within the vaccination programme are reported to a central register, which we linked to demographic information found in the Danish civil register. We calculated vaccination uptake and used Cox regression survival analysis to compare the uptake rates between demographic subgroups in the population, e.g. by number of siblings, age of mother (at the daughter's birth) and place of origin. The uptake among the 33,838 eligible girls was 80%, 75% and 62% respectively for the three HPV-doses. All subgroups had uptake above 68% for the first HPV-vaccination. Girls with mothers younger or older than the reference group of 25-34 years had a lower uptake rate (adjHR 0.94, 95% CI 0.91-0.97 and adjHR 0.91, 95% CI 0.88-0.94 respectively). Girls with 5 or more siblings had lower uptake rate than girls without siblings (adjHR 0.79, 95% CI 0.71-0.87). Girls born in other EU/EFTA-countries had lower uptake rate than Danish-born girls with Danish-born parents (adjHR 0.74, 95% CI 0.67-0.82). The introduction of routine HPV-vaccination in Denmark resulted in a relatively high uptake, indicating little reason for major concern about barriers towards the vaccination in Denmark. Population groups with reduced uptake were identified, but as they were small in number their effect on the overall vaccination coverage was marginal. Nonetheless, these groups should be targeted in future acceptance studies and vaccination awareness campaigns. Copyright © 2011 Elsevier Ltd. All rights reserved.

Private-sector vaccine purchase costs and insurer payments: a disincentive for using combination vaccines?

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Clark, Sarah J; Cowan, Anne E; Freed, Gary L

2011-04-01

Combination vaccines have been endorsed as a means to decrease the number of injections needed to complete the childhood immunization schedule, yet anecdotal reports suggest that private providers lose money on combination vaccines. The objective of this study was to determine whether practices purchasing combination vaccines had significantly different vaccine costs and reimbursement compared to practices that were not purchasing combination vaccines. Using cross-sectional purchase and insurer payment data collected from a targeted sample of private practices in five US states, we calculated the average total vaccine cost and reimbursement across the childhood immunization schedule. The average vaccine purchase cost across the childhood schedule was significantly higher for practices using a combined vaccine with diphtheria, tetanus, acellular pertussis vaccine, inactivated polio vaccine, and Hepatitis B vaccine (DTaP-IPV-HepB) than for practices using either separate vaccine products or a combined vaccine with Haemophilus influenzae, type b vaccine and Hepatitis B vaccine (Hib-HepB). The average insurer payment for vaccine administration across the childhood schedule was significantly lower for practices using DTaP-IPV-HepB combination vaccine than for practices using separate vaccine products. This study appears to validate anecdotal reports that vaccine purchase costs and insurer payment for combination vaccines can have a negative financial impact for practices that purchase childhood vaccines.

Immune Suppression in Tumors as a Surmountable Obstacle to Clinical Efficacy of Cancer Vaccines

International Nuclear Information System (INIS)

Wieërs, Grégoire; Demotte, Nathalie; Godelaine, Danièle; Bruggen, Pierre van der

2011-01-01

Human tumors are usually not spontaneously eliminated by the immune system and therapeutic vaccination of cancer patients with defined antigens is followed by tumor regressions only in a small minority of the patients. The poor vaccination effectiveness could be explained by an immunosuppressive tumor microenvironment. Because T cells that infiltrate tumor metastases have an impaired ability to lyse target cells or to secrete cytokine, many researchers are trying to decipher the underlying immunosuppressive mechanisms. We will review these here, in particular those considered as potential therapeutic targets. A special attention will be given to galectins, a family of carbohydrate binding proteins. These lectins have often been implicated in inflammation and cancer and may be useful targets for the development of new anti-cancer therapies

Mucosal vaccination with heterologous viral vectored vaccine targeting subdominant SIV accessory antigens strongly inhibits early viral replication

DEFF Research Database (Denmark)

Xu, Huanbin; Andersson, Anne-Marie Carola; Ragonnaud, Emeline

2017-01-01

Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat...

Negative attitude of highly educated parents and health care workers towards future vaccinations in the Dutch childhood vaccination program

NARCIS (Netherlands)

Hak, E; Schönbeck, Y; De Melker, H; Van Essen, G A; Sanders, E A M

2005-01-01

BACKGROUND: It is unknown whether further expansion of the Dutch childhood vaccination program with other vaccines will be accepted and whom should be targeted in educational strategies. AIM: To determine attitudes of parents towards possible future vaccinations for their children and the

Monitoring what governments "give for" and "spend on" vaccine procurement: Vaccine Procurement Assistance and Vaccine Procurement Baseline.

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E A S Nelson

Full Text Available BACKGROUND: The Global Vaccine Action Plan will require, inter alia, the mobilization of financial resources from donors and national governments - both rich and poor. Vaccine Procurement Assistance (VPA and Vaccine Procurement Baseline (VPB are two metrics that could measure government performance and track resources in this arena. VPA is proposed as a new subcategory of Official Development Assistance (ODA given for the procurement of vaccines and VPB is a previously suggested measure of the share of Gross Domestic Product (GDP that governments spend on their own vaccine procurement. OBJECTIVE: To determine realistic targets for VPA and VPB. METHODS: Organization for Economic Co-Operation and Development (OECD and World Bank data for 2009 were analyzed to determine the proportions of bilateral ODA from the 23 Development Assistance Committee (DAC countries disbursed (as % of GDP in current US$ for infectious disease control. DAC country contributions to the GAVI Alliance for 2009 were assessed as a measure of multilateral donor support for vaccines and immunization programs. FINDINGS: In 2009, total DAC bilateral ODA was 0.16% of global GDP and 0.25% of DAC GDP. As a percentage of GDP, Norway (0.013% and United Kingdom (0.0085% disbursed the greatest proportion of bilateral ODA for infectious disease control, and Norway (0.024% and Canada (0.008% made the greatest contributions to the GAVI Alliance. In 2009 0.02% of DAC GDP was US$7.61 billion and 0.02% of the GDP of the poorest 117 countries was US$2.88 billion. CONCLUSIONS: Adopting 0.02% GDP as minimum targets for both VPA and VPB is based on realistic estimates of what both developed and developing countries should spend, and can afford to spend, to jointly ensure procurement of vaccines recommended by national and global bodies. New OECD purpose codes are needed to specifically track ODA disbursed for a vaccine procurement; and b immunization programs.

The PEP-3-KLH (CDX-110) vaccine in glioblastoma multiforme patients

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Heimberger, Amy B.; Sampson, John H

2009-01-01

Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively resulting in non-specific toxicity. Immune targeting of tumor-specific mutations may allow for more precise eradication of neoplastic cells. The epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation that is widely expressed on GBM and other neoplasms and its expression enhances tumorigenicity. This in-frame deletion mutation splits a codon resulting in a novel glycine at the fusion junction producing a tumor-specific epitope target for cellular or humoral immunotherapy. We have previously shown that vaccination with a peptide that spans the EGFRvIII fusion junction (PEPvIII-KLH/CDX-110) is an efficacious immunotherapy in syngeneic murine models. In this review, we summarize our results in GBM patients targeting this mutation in multiple, multi-institutional Phase II immunotherapy trials. These trials demonstrated that a selected population of GBM patients who received the vaccines targeting EGFRvIII had an unexpectedly long survival time. Further therapeutic strategies and potential pitfalls using this approach are discussed. PMID:19591631

Identification of pre-erythrocytic malaria antigens that target hepatocytes for killing in vivo and contribute to protection elicited by whole-parasite vaccination.

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Lin Chen

Full Text Available Pre-erythrocytic malaria vaccines, including those based on whole-parasite approaches, have shown protective efficacy in animal and human studies. However few pre-erythocytic antigens other than the immunodominant circumsporozoite protein (CSP have been studied in depth with the goal of developing potent subunit malaria vaccines that are suited for use in endemic areas. Here we describe a novel technique to identify pre-erythrocytic malaria antigens that contribute to protection elicited by whole-parasite vaccination in the mouse model. Our approach combines immunization with genetically attenuated parasites and challenge with DNA plasmids encoding for potential protective pre-erythrocytic malaria antigens as luciferase fusions by hydrodynamic tail vein injection. After optimizing the technique, we first showed that immunization with Pyfabb/f-, a P. yoelii genetically attenuated parasite, induces killing of CSP-presenting hepatocytes. Depletion of CD8+ but not CD4+ T cells diminished the killing of CSP-expressing hepatocytes, indicating that killing is CD8+ T cell-dependent. Finally we showed that the use of heterologous prime/boost immunization strategies that use genetically attenuated parasites and DNA vaccines enabled the characterization of a novel pre-erythrocytic antigen, Tmp21, as a contributor to Pyfabb/f- induced protection. This technique will be valuable for identification of potentially protective liver stage antigens and has the potential to contribute to the understanding of immunity elicited by whole parasite vaccination, as well as the development of effective subunit malaria vaccines.

Contrasting female-male mortality ratios after routine vaccinations with pentavalent vaccine versus measles and yellow fever vaccine. A cohort study from urban Guinea-Bissau

DEFF Research Database (Denmark)

Fisker, Ane B; Biering-Sørensen, Sofie; Lund, Najaaraq

2016-01-01

, DTP vaccine is associated with increased female mortality relative to male mortality. In 2008, Guinea-Bissau replaced DTP with the DTP-containing pentavalent vaccine (Penta; DTP-H. influenza type B-Hepatitis B) at 6, 10 and 14weeks and yellow fever vaccine (YF) was to be given with MV. We investigated......BACKGROUND: In addition to protection against the target diseases, vaccines may have non-specific effects (NSEs). Measles vaccine (MV) has beneficial NSEs, providing protection against non-measles deaths, most so for girls. By contrast, though protecting against diphtheria, tetanus and pertussis...... possible sex-differential mortality rates following Penta and MV+YF vaccination. METHODS: Bandim Health Project (BHP) registers vaccines given by the three government health centres in the study area and vital status through demographic surveillance. We assessed the association between sex and mortality...

Adolescent Premature Ovarian Insufficiency Following Human Papillomavirus Vaccination

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Deirdre Therese Little MBBS, DRANZCOG, FACRRM

2014-10-01

Full Text Available Three young women who developed premature ovarian insufficiency following quadrivalent human papillomavirus (HPV vaccination presented to a general practitioner in rural New South Wales, Australia. The unrelated girls were aged 16, 16, and 18 years at diagnosis. Each had received HPV vaccinations prior to the onset of ovarian decline. Vaccinations had been administered in different regions of the state of New South Wales and the 3 girls lived in different towns in that state. Each had been prescribed the oral contraceptive pill to treat menstrual cycle abnormalities prior to investigation and diagnosis. Vaccine research does not present an ovary histology report of tested rats but does present a testicular histology report. Enduring ovarian capacity and duration of function following vaccination is unresearched in preclinical studies, clinical and postlicensure studies. Postmarketing surveillance does not accurately represent diagnoses in adverse event notifications and can neither represent unnotified cases nor compare incident statistics with vaccine course administration rates. The potential significance of a case series of adolescents with idiopathic premature ovarian insufficiency following HPV vaccination presenting to a general practice warrants further research. Preservation of reproductive health is a primary concern in the recipient target group. Since this group includes all prepubertal and pubertal young women, demonstration of ongoing, uncompromised safety for the ovary is urgently required. This matter needs to be resolved for the purposes of population health and public vaccine confidence.

Adapting to the global shortage of cholera vaccines: targeted single dose cholera vaccine in response to an outbreak in South Sudan.

Science.gov (United States)

Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Ciglenecki, Iza; Luquero, Francisco J; Azman, Andrew S; Cabrol, Jean-Clement

2017-04-01

Shortages of vaccines for epidemic diseases, such as cholera, meningitis, and yellow fever, have become common over the past decade, hampering efforts to control outbreaks through mass reactive vaccination campaigns. Additionally, various epidemiological, political, and logistical challenges, which are poorly documented in the literature, often lead to delays in reactive campaigns, ultimately reducing the effect of vaccination. In June 2015, a cholera outbreak occurred in Juba, South Sudan, and because of the global shortage of oral cholera vaccine, authorities were unable to secure sufficient doses to vaccinate the entire at-risk population-approximately 1 million people. In this Personal View, we document the first public health use of a reduced, single-dose regimen of oral cholera vaccine, and show the details of the decision-making process and timeline. We also make recommendations to help improve reactive vaccination campaigns against cholera, and discuss the importance of new and flexible context-specific dose regimens and vaccination strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

A computational method for identification of vaccine targets from protein regions of conserved human leukocyte antigen binding

DEFF Research Database (Denmark)

Olsen, Lars Rønn; Simon, Christian; Kudahl, Ulrich J.

2015-01-01

Background: Computational methods for T cell-based vaccine target discovery focus on selection of highly conserved peptides identified across pathogen variants, followed by prediction of their binding of human leukocyte antigen molecules. However, experimental studies have shown that T cells ofte...... or proteome using human leukocyte antigen binding predictions and made a web-accessible software implementation freely available at http://met-hilab.cbs.dtu.dk/blockcons/....

Vaccine development for syphilis.

Science.gov (United States)

Lithgow, Karen V; Cameron, Caroline E

2017-01-01

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.

Mature Epitope Density - A strategy for target selection based on immunoinformatics and exported prokaryotic proteins

DEFF Research Database (Denmark)

Santos, Anderson R; Pereira, Vanessa Bastos; Barbosa, Eudes

2013-01-01

. However, currently available tools do not account for the concentration of epitope products in the mature protein product and its relation to the reliability of target selection. RESULTS: We developed a computational strategy based on measuring the epitope's concentration in the mature protein, called...... Mature Epitope Density (MED). Our method, though simple, is capable of identifying promising vaccine targets. Our online software implementation provides a computationally light and reliable analysis of bacterial exoproteins and their potential for vaccines or diagnosis projects against pathogenic...... proteins were confirmed as related. There was no experimental evidence of antigenic or pathogenic contributions for three of the highest MED-scored Mtb proteins. Hence, these three proteins could represent novel putative vaccine and drug targets for Mtb. A web version of MED is publicly available online...

A Cross-Sectional Study to Assess HPV Knowledge and HPV Vaccine Acceptability in Mali

Science.gov (United States)

Poole, Danielle N.; Tracy, J. Kathleen; Levitz, Lauren; Rochas, Mali; Sangare, Kotou; Yekta, Shahla; Tounkara, Karamoko; Aboubacar, Ben; Koita, Ousmane; Lurie, Mark; De Groot, Anne S.

2013-01-01

Despite a high prevalence of oncogenic human papilloma virus (HPV) infection and cervical cancer mortality, HPV vaccination is not currently available in Mali. Knowledge of HPV and cervical cancer in Mali, and thereby vaccine readiness, may be limited. Research staff visited homes in a radial pattern from a central location to recruit adolescent females and males aged 12–17 years and men and women aged ≥18 years (N = 51) in a peri-urban village of Bamako, Mali. Participants took part in structured interviews assessing knowledge, attitudes, and practices related to HPV, cervical cancer, and HPV vaccination. We found low levels of HPV and cervical cancer knowledge. While only 2.0% of respondents knew that HPV is a sexually transmitted infection (STI), 100% said they would be willing to receive HPV vaccination and would like the HPV vaccine to be available in Mali. Moreover, 74.5% said they would vaccinate their child(ren) against HPV. Men were found to have significantly greater autonomy in the decision to vaccinate themselves than women and adolescents (p = 0.005), a potential barrier to be addressed by immunization campaigns. HPV vaccination would be highly acceptable if the vaccine became widely available in Bamako, Mali. This study demonstrates the need for a significant investment in health education if truly informed consent is to be obtained for HPV vaccination. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine. Barriers to vaccination, including the significantly lower ability of the majority of the target population to autonomously decide to get vaccinated, must also be addressed in future HPV vaccine campaigns. PMID:23431375

A cross-sectional study to assess HPV knowledge and HPV vaccine acceptability in Mali.

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Danielle N Poole

Full Text Available Despite a high prevalence of oncogenic human papilloma virus (HPV infection and cervical cancer mortality, HPV vaccination is not currently available in Mali. Knowledge of HPV and cervical cancer in Mali, and thereby vaccine readiness, may be limited. Research staff visited homes in a radial pattern from a central location to recruit adolescent females and males aged 12-17 years and men and women aged ≥ 18 years (N = 51 in a peri-urban village of Bamako, Mali. Participants took part in structured interviews assessing knowledge, attitudes, and practices related to HPV, cervical cancer, and HPV vaccination. We found low levels of HPV and cervical cancer knowledge. While only 2.0% of respondents knew that HPV is a sexually transmitted infection (STI, 100% said they would be willing to receive HPV vaccination and would like the HPV vaccine to be available in Mali. Moreover, 74.5% said they would vaccinate their child(ren against HPV. Men were found to have significantly greater autonomy in the decision to vaccinate themselves than women and adolescents (p = 0.005, a potential barrier to be addressed by immunization campaigns. HPV vaccination would be highly acceptable if the vaccine became widely available in Bamako, Mali. This study demonstrates the need for a significant investment in health education if truly informed consent is to be obtained for HPV vaccination. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine. Barriers to vaccination, including the significantly lower ability of the majority of the target population to autonomously decide to get vaccinated, must also be addressed in future HPV vaccine campaigns.

Timeliness vaccination of measles containing vaccine and barriers to vaccination among migrant children in East China.

Directory of Open Access Journals (Sweden)

Yu Hu

Full Text Available BACKGROUND: The reported coverage rates of first and second doses of measles containing vaccine (MCV are almost 95% in China, while measles cases are constantly being reported. This study evaluated the vaccine coverage, timeliness, and barriers to immunization of MCV1 and MCV2 in children aged from 8-48 months. METHODS: We assessed 718 children aged 8-48 months, of which 499 children aged 18-48 months in September 2011. Face to face interviews were administered with children's mothers to estimate MCV1 and MCV2 coverage rate, its timeliness and barriers to vaccine uptake. RESULTS: The coverage rates were 76.9% for MCV1 and 44.7% for MCV2 in average. Only 47.5% of surveyed children received the MCV1 timely, which postpone vaccination by up to one month beyond the stipulated age of 8 months. Even if coverage thus improves with time, postponed vaccination adds to the pool of unprotected children in the population. Being unaware of the necessity for vaccination and its schedule, misunderstanding of side-effect of vaccine, and child being sick during the recommended vaccination period were significant preventive factors for both MCV1 and MCV2 vaccination. Having multiple children, mother's education level, household income and children with working mothers were significantly associated with delayed or missing MCV1 immunization. CONCLUSIONS: To avoid future outbreaks, it is crucial to attain high coverage levels by timely vaccination, thus, accurate information should be delivered and a systematic approach should be targeted to high-risk groups.

Vaccine supply chains need to be better funded and strengthened, or lives will be at risk.

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Kaufmann, Judith R; Miller, Roger; Cheyne, James

2011-06-01

In the next decade, at least twelve additional vaccines that target such diseases as typhoid, malaria, and dengue will become available to lower- and middle-income countries. These vaccines must travel along what are called supply chains, which include all personnel, systems, equipment, and activities involved in ensuring that vaccines are effectively delivered from the point of production to the people who need them. But for various reasons, supply chains are already strained in many developing countries, and the potential inability to distribute new vaccines will place lives at risk. Among the many steps needed to strengthen the global vaccine supply chain, we suggest that the international community pursue improved coordination between organizations that donate and ship vaccines and the host-country officials who receive and distribute the vaccines, as well as better training for supply-chain managers.

Vaccine development against Leishmania donovani

Directory of Open Access Journals (Sweden)

Amrita eDas

2012-05-01

Full Text Available Visceral leishmaniasis (VL caused by Leishmania donovani and Leishmania infantum/ chagasi represents the second most challenging infectious disease worldwide, affecting nearly 500,000 people and 60,000 deaths annually. Zoonotic VL (ZVL caused by L. infantum is re-emergent canid zoonoses which represents a complex epidemiological cycle in New world where domestic dogs serve as reservoir host responsible for potentially fatal human infection where dog culling is the only control measure for eliminating reservoir host. Lifelong immunity in human against reinfection has motivated several attempts in developing prophylactic vaccines against the disease but very few have progressed beyond experimental stage. Absence of any licensed vaccine along with high toxicity and increasing resistance to the current chemotherapeutic drugs has further complicated the situation in endemic regions of the world. Advances in vaccinology, including recombinant proteins, novel antigen-delivery systems/adjuvants, heterologous prime-boost regimens and strategies for intracellular antigen presentation, have contributed to recent advances in vaccine development against VL. Attempts to develop an effective vaccine for use in domestic dogs in areas of canine VL should be pursued for preventing human infection. Studies in animal models and human patients have revealed the pathogenic mechanisms of disease progression and features of protective immunity. This review will summarize the accumulated knowledge about pathogenesis, immune response and prerequisites for protective immunity against human VL. Authors will discuss promising vaccine targets, their developmental status and future prospects in a quest for rational vaccine development against VL. In addition, several challenges such as safety issues, a renewed and coordinated commitment to basic research, preclinical studies and trial design will be addressed to overcome the problems faced in developing effective vaccines

Biologic interactions between HSV-2 and HIV-1 and possible implications for HSV vaccine development.

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Schiffer, Joshua T; Gottlieb, Sami L

2017-09-25

Development of a safe and effective vaccine against herpes simplex virus type 2 (HSV-2) has the potential to limit the global burden of HSV-2 infection and disease, including genital ulcer disease and neonatal herpes, and is a global sexual and reproductive health priority. Another important potential benefit of an HSV-2 vaccine would be to decrease HIV infections, as HSV-2 increases the risk of HIV-1 acquisition several-fold. Acute and chronic HSV-2 infection creates ulcerations and draws dendritic cells and activated CD4+ T cells into genital mucosa. These cells are targets for HIV entry and replication. Prophylactic HSV-2 vaccines (to prevent infection) and therapeutic vaccines (to modify or treat existing infections) are currently under development. By preventing or modifying infection, an effective HSV-2 vaccine could limit HSV-associated genital mucosal inflammation and thus HIV risk. However, a vaccine might have competing effects on HIV risk depending on its mechanism of action and cell populations generated in the genital mucosa. In this article, we review biologic interactions between HSV-2 and HIV-1, consider HSV-2 vaccine development in the context of HIV risk, and discuss implications and research needs for future HSV vaccine development. Copyright © 2017 Elsevier Ltd. All rights reserved.

The safety of influenza vaccines in children: An Institute for Vaccine Safety white paper.

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Halsey, Neal A; Talaat, Kawsar R; Greenbaum, Adena; Mensah, Eric; Dudley, Matthew Z; Proveaux, Tina; Salmon, Daniel A

2015-12-30

Most influenza vaccines are generally safe, but influenza vaccines can cause rare serious adverse events. Some adverse events, such as fever and febrile seizures, are more common in children than adults. There can be differences in the safety of vaccines in different populations due to underlying differences in genetic predisposition to the adverse event. Live attenuated vaccines have not been studied adequately in children under 2 years of age to determine the risks of adverse events; more studies are needed to address this and several other priority safety issues with all influenza vaccines in children. All vaccines intended for use in children require safety testing in the target age group, especially in young children. Safety of one influenza vaccine in children should not be extrapolated to assumed safety of all influenza vaccines in children. The low rates of adverse events from influenza vaccines should not be a deterrent to the use of influenza vaccines because of the overwhelming evidence of the burden of disease due to influenza in children. Copyright © 2016. Published by Elsevier Ltd.

Rapid DNA vaccination against Burkholderia pseudomallei flagellin by tattoo or intranasal application.

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Lankelma, Jacqueline M; Wagemakers, Alex; Birnie, Emma; Haak, Bastiaan W; Trentelman, Jos J A; Weehuizen, Tassili A F; Ersöz, Jasmin; Roelofs, Joris J T H; Hovius, Joppe W; Wiersinga, W Joost; Bins, Adriaan D

2017-11-17

Melioidosis is a severe infectious disease with a high mortality that is endemic in South-East Asia and Northern Australia. The causative pathogen, Burkholderia pseudomallei, is listed as potential bioterror weapon due to its high virulence and potential for easy dissemination. Currently, there is no licensed vaccine for prevention of melioidosis. Here, we explore the use of rapid plasmid DNA vaccination against B. pseudomallei flagellin for protection against respiratory challenge. We tested three flagellin DNA vaccines with different subcellular targeting designs. C57BL/6 mice were vaccinated via skin tattoo on day 0, 3 and 6 before intranasal challenge with B. pseudomallei on day 21. Next, the most effective construct was used as single vaccination on day 0 by tattoo or intranasal formulation. Mice were sacrificed 72 hours post-challenge to assess bacterial loads, cytokine responses, inflammation and microscopic lesions. A construct encoding a cellular secretion signal resulted in the most effective protection against melioidosis via tattooing, with a 10-fold reduction in bacterial loads in lungs and distant organs compared to the empty vector. Strikingly, a single intranasal administration of the same vaccine resulted in >1000-fold lower bacterial loads and increased survival. Pro-inflammatory cytokine responses were significantly diminished and strong reductions in markers for distant organ damage were observed. A rapid vaccination scheme using flagellin DNA tattoo provides significant protection against intranasal challenge with B. pseudomallei, markedly improved by a single administration via airway mucosa. Hence intranasal vaccination with flagellin-encoding DNA may be applicable when acute mass vaccination is indicated and warrants further testing.

Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120.

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deCamp, Allan C; Rolland, Morgane; Edlefsen, Paul T; Sanders-Buell, Eric; Hall, Breana; Magaret, Craig A; Fiore-Gartland, Andrew J; Juraska, Michal; Carpp, Lindsay N; Karuna, Shelly T; Bose, Meera; LePore, Steven; Miller, Shana; O'Sullivan, Annemarie; Poltavee, Kultida; Bai, Hongjun; Dommaraju, Kalpana; Zhao, Hong; Wong, Kim; Chen, Lennie; Ahmed, Hasan; Goodman, Derrick; Tay, Matthew Z; Gottardo, Raphael; Koup, Richard A; Bailer, Robert; Mascola, John R; Graham, Barney S; Roederer, Mario; O'Connell, Robert J; Michael, Nelson L; Robb, Merlin L; Adams, Elizabeth; D'Souza, Patricia; Kublin, James; Corey, Lawrence; Geraghty, Daniel E; Frahm, Nicole; Tomaras, Georgia D; McElrath, M Juliana; Frenkel, Lisa; Styrchak, Sheila; Tovanabutra, Sodsai; Sobieszczyk, Magdalena E; Hammer, Scott M; Kim, Jerome H; Mullins, James I; Gilbert, Peter B

2017-01-01

Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 sequences from vaccine recipients were significantly more distant from the subtype B vaccine insert than sequences from placebo recipients (P = 0.01, Q-value = 0.12). These vaccine effects were associated with signatures mapping to CD4 binding site and CD4-induced monoclonal antibody footprints. These results suggest either (i) no vaccine efficacy to block acquisition of any viral genotype but vaccine-accelerated Env evolution post-acquisition; or (ii) vaccine efficacy against HIV-1s with Env sequences closest to the vaccine insert combined with increased acquisition due to other factors, potentially including the vaccine vector.

The Potential of Vaccines for the Control of AIDS

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Margaret I Johnston

1994-01-01

of attenuated and whole-killed products have led to the pursuit of alternativc designs. including recombinant proteins, vectors and particles, synthetic peptides and naked DNA. Seven recombinant envelope. two recombinant vector and four other candidate vaccines that have entered into phase 1 trials in noninfected individuals have proven safe to date, and have differed In their ability lo induce functional antibody and Cytotoxic T lymphocytes. Two recombinant envelope products have recently progressed to phase 2 testing, Five envelope-based and six other products have entered trial in HIV-infected and individuals and have appeared to be safe, Evidence of new antibody, increased T cell proliferation and lncreased cytotoxic T lymphocyte activity have been reported. Additional placebo controlled trials will be required to evaluate the impact of therapeutic vaccination on CD4 cell count. viral burdrn and clinical end-points. The status of HIV/AIDS vaccine development is reviewed. with emphasis on the challenging task of finding an effieacious, safe, prophylactic vaccine.

The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia): A Model Comparison Study.

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Flasche, Stefan; Jit, Mark; Rodríguez-Barraquer, Isabel; Coudeville, Laurent; Recker, Mario; Koelle, Katia; Milne, George; Hladish, Thomas J; Perkins, T Alex; Cummings, Derek A T; Dorigatti, Ilaria; Laydon, Daniel J; España, Guido; Kelso, Joel; Longini, Ira; Lourenco, Jose; Pearson, Carl A B; Reiner, Robert C; Mier-Y-Terán-Romero, Luis; Vannice, Kirsten; Ferguson, Neil

2016-11-01

both Phase III trials. In contrast, in settings with low transmission intensity (SP9 ≤ 30%), the models predicted that vaccination could lead to a substantial increase in hospitalisation because of dengue. Modelling reduced vaccine coverage or the addition of catch-up campaigns showed that the impact of vaccination scaled approximately linearly with the number of people vaccinated. In assessing the optimal age of vaccination, we found that targeting older children could increase the net benefit of vaccination in settings with moderate transmission intensity (SP9 = 50%). Overall, vaccination was predicted to be potentially cost-effective in most endemic settings if priced competitively. The results are based on the assumption that the vaccine acts similarly to natural infection. This assumption is consistent with the available trial results but cannot be directly validated in the absence of additional data. Furthermore, uncertainties remain regarding the level of protection provided against disease versus infection and the rate at which vaccine-induced protection declines. Dengvaxia has the potential to reduce the burden of dengue disease in areas of moderate to high dengue endemicity. However, the potential risks of vaccination in areas with limited exposure to dengue as well as the local costs and benefits of routine vaccination are important considerations for the inclusion of Dengvaxia into existing immunisation programmes. These results were important inputs into WHO global policy for use of this licensed dengue vaccine.

The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia: A Model Comparison Study.

Directory of Open Access Journals (Sweden)

Stefan Flasche

2016-11-01

participating sites in both Phase III trials. In contrast, in settings with low transmission intensity (SP9 ≤ 30%, the models predicted that vaccination could lead to a substantial increase in hospitalisation because of dengue. Modelling reduced vaccine coverage or the addition of catch-up campaigns showed that the impact of vaccination scaled approximately linearly with the number of people vaccinated. In assessing the optimal age of vaccination, we found that targeting older children could increase the net benefit of vaccination in settings with moderate transmission intensity (SP9 = 50%. Overall, vaccination was predicted to be potentially cost-effective in most endemic settings if priced competitively. The results are based on the assumption that the vaccine acts similarly to natural infection. This assumption is consistent with the available trial results but cannot be directly validated in the absence of additional data. Furthermore, uncertainties remain regarding the level of protection provided against disease versus infection and the rate at which vaccine-induced protection declines.Dengvaxia has the potential to reduce the burden of dengue disease in areas of moderate to high dengue endemicity. However, the potential risks of vaccination in areas with limited exposure to dengue as well as the local costs and benefits of routine vaccination are important considerations for the inclusion of Dengvaxia into existing immunisation programmes. These results were important inputs into WHO global policy for use of this licensed dengue vaccine.

Assessing the Potential Cost-Effectiveness of Microneedle Patches in Childhood Measles Vaccination Programs: The Case for Further Research and Development.

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Adhikari, Bishwa B; Goodson, James L; Chu, Susan Y; Rota, Paul A; Meltzer, Martin I

2016-12-01

Currently available measles vaccines are administered by subcutaneous injections and require reconstitution with a diluent and a cold chain, which is resource intensive and challenging to maintain. To overcome these challenges and potentially increase vaccination coverage, microneedle patches are being developed to deliver the measles vaccine. This study compares the cost-effectiveness of using microneedle patches with traditional vaccine delivery by syringe-and-needle (subcutaneous vaccination) in children's measles vaccination programs. We built a simple spreadsheet model to compute the vaccination costs for using microneedle patch and syringe-and-needle technologies. We assumed that microneedle vaccines will be, compared with current vaccines, more heat stable and require less expensive cool chains when used in the field. We used historical data on the incidence of measles among communities with low measles vaccination rates. The cost of microneedle vaccination was estimated at US$0.95 (range US$0.71-US$1.18) for the first dose, compared with US$1.65 (range US$1.24-US$2.06) for the first dose delivered by subcutaneous vaccination. At 95 % vaccination coverage, microneedle patch vaccination was estimated to cost US$1.66 per measles case averted (range US$1.24-US$2.07) compared with an estimated cost of US$2.64 per case averted (range US$1.98-US$3.30) using subcutaneous vaccination. Use of microneedle patches may reduce costs; however, the cost-effectiveness of patches would depend on the vaccine recipients' acceptability and vaccine effectiveness of the patches relative to the existing conventional vaccine-delivery method. This study emphasizes the need to continue research and development of this vaccine-delivery method that could boost measles elimination efforts through improved access to vaccines and increased vaccination coverage.

In “Step” with HIV Vaccines? A Content Analysis of Local Recruitment Campaigns for an International HIV Vaccine Study

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Frew, Paula M.; Macias, Wendy; Chan, Kayshin; Harding, Ashley C.

2009-01-01

During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the “Step Study”). This study examined persuasive features consistent with the Elaboration Likelihood Model (ELM) including message content, personal relevance of HIV/AIDS and vaccine research, intended audiences, information sources, and other contextual features. The results indicated variation in messages and communication approaches with gay men more exclusively targeted in these regions. Racial/ethnic representations also differed by campaign. Most of the materials promote affective evaluation of the information through heuristic cueing. Implications for subsequent campaigns and research directions are discussed. PMID:19609373

Applications of nanomaterials as vaccine adjuvants

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Zhu, Motao; Wang, Rongfu; Nie, Guangjun

2014-01-01

Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigen-specific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials’ physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants. PMID:25483497

Design of therapeutic vaccines as a novel antibody therapy for cardiovascular diseases.

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Nakagami, Hironori

2017-09-01

Vaccines are primarily used worldwide as a preventive medicine for infectious diseases and have recently been applied to cancer. We and others have developed therapeutic vaccines designed for cardiovascular diseases that are notably different from previous vaccines. In the case of cancer vaccines, a specific protein in cancer cells is a target antigen, and the activation of cytotoxic T cells (CTL) is required to kill and remove the antigen-presenting cancer cells. Our therapeutic vaccines work against hypertension by targeting angiotensin II (Ang II) as the antigen, which is an endogenous hormone. Therapeutic vaccines must avoid CTL activation and induce the blocking antibodies for Ang II. The goal of our therapeutic vaccine for cardiovascular diseases is to induce the specific antibody response toward the target protein without inducing T-cell or antibody-mediated inflammation through the careful selection of the target antigen, carrier protein and adjuvants. The goal of our therapeutic vaccine is similar to that of antibody therapy. Recently, multiple antibody-based drugs have been developed for cancer, immune-related diseases, and dyslipidemia, which are efficient but expensive. If the effect of a therapeutic vaccine is nearly equivalent to antibody therapy as an alternative approach, the lower medical cost and improvement in drug adherence can be advantages of therapeutic vaccines. In this review, we will describe our concept of therapeutic vaccines for cardiovascular diseases and the future directions of therapeutic vaccines as novel antibody therapies. Copyright © 2017. Published by Elsevier Ltd.

Vaccination targeting human HER3 alters the phenotype of infiltrating T cells and responses to immune checkpoint inhibition.

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Osada, Takuya; Morse, Michael A; Hobeika, Amy; Diniz, Marcio A; Gwin, William R; Hartman, Zachary; Wei, Junping; Guo, Hongtao; Yang, Xiao-Yi; Liu, Cong-Xiao; Kaneko, Kensuke; Broadwater, Gloria; Lyerly, H Kim

2017-01-01

Expression of human epidermal growth factor family member 3 (HER3), a critical heterodimerization partner with EGFR and HER2, promotes more aggressive biology in breast and other epithelial malignancies. As such, inhibiting HER3 could have broad applicability to the treatment of EGFR- and HER2-driven tumors. Although lack of a functional kinase domain limits the use of receptor tyrosine kinase inhibitors, HER3 contains antigenic targets for T cells and antibodies. Using novel human HER3 transgenic mouse models of breast cancer, we demonstrate that immunization with recombinant adenoviral vectors encoding full length human HER3 (Ad-HER3-FL) induces HER3-specific T cells and antibodies, alters the T cell infiltrate in tumors, and influences responses to immune checkpoint inhibitions. Both preventative and therapeutic Ad-HER3-FL immunization delayed tumor growth but were associated with both intratumoral PD-1 expressing CD8 + T cells and regulatory CD4 + T cell infiltrates. Immune checkpoint inhibition with either anti-PD-1 or anti-PD-L1 antibodies increased intratumoral CD8 + T cell infiltration and eliminated tumor following preventive vaccination with Ad-HER3-FL vaccine. The combination of dual PD-1/PD-L1 and CTLA4 blockade slowed the growth of tumor in response to Ad-HER3-FL in the therapeutic model. We conclude that HER3-targeting vaccines activate HER3-specific T cells and induce anti-HER3 specific antibodies, which alters the intratumoral T cell infiltrate and responses to immune checkpoint inhibition.

Juvenile-specific cathepsin proteases in Fasciola spp.: their characteristics and vaccine efficacies.

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Meemon, Krai; Sobhon, Prasert

2015-08-01

Fasciolosis, caused by Fasciola hepatica and Fasciola gigantica, is one of the most neglected tropical zoonotic diseases. One sustainable control strategy against these infections is the employment of vaccines that target proteins essential for parasites' invasion and nutrition acquiring processes. Cathepsin proteases are the most abundantly expressed proteins in Fasciola spp. that have been tested successfully as vaccines against fasciolosis in experimental as well as large animals because of their important roles in digestion of nutrients, invasion, and migration. Specifically, juvenile-specific cathepsin proteases are the more effective vaccines because they could block the invasion and migration of juvenile parasites whose immune evasion mechanism has not yet been fully developed. Moreover, because of high sequence similarity and identity of cathepsins from juveniles with those of adults, the vaccines can attack both the juvenile and adult stages. In this article, the characteristics and vaccine potentials of juvenile-specific cathepsins, i.e., cathepsins L and B, of Fasciola spp. were reviewed.

Childhood vaccines and Kawasaki disease, Vaccine Safety Datalink, 1996-2006.

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Abrams, Joseph Y; Weintraub, Eric S; Baggs, James M; McCarthy, Natalie L; Schonberger, Lawrence B; Lee, Grace M; Klein, Nicola P; Belongia, Edward A; Jackson, Michael L; Naleway, Allison L; Nordin, James D; Hambidge, Simon J; Belay, Ermias D

2015-01-03

Kawasaki disease is a childhood vascular disorder of unknown etiology. Concerns have been raised about vaccinations being a potential risk factor for Kawasaki disease. Data from the Vaccine Safety Datalink were collected on children aged 0-6 years at seven managed care organizations across the United States. Defining exposure as one of several time periods up to 42 days after vaccination, we conducted Poisson regressions controlling for age, sex, season, and managed care organization to determine if rates of physician-diagnosed and verified Kawasaki disease were elevated following vaccination compared to rates during all unexposed periods. We also performed case-crossover analyses to control for unmeasured confounding. A total of 1,721,186 children aged 0-6 years from seven managed care organizations were followed for a combined 4,417,766 person-years. The rate of verified Kawasaki disease was significantly lower during the 1-42 days after vaccination (rate ratio=0.50, 95% CL=0.27-0.92) and 8-42 days after vaccination (rate ratio=0.45, 95% CL=0.22-0.90) compared to rates during unexposed periods. Breaking down the analysis by vaccination category did not identify a subset of vaccines which was solely responsible for this association. The case-crossover analyses revealed that children with Kawasaki disease had lower rates of vaccination in the 42 days prior to symptom onset for both physician-diagnosed Kawasaki disease (rate ratio=0.79, 95% CL=0.64-0.97) and verified Kawasaki disease (rate ratio=0.38, 95% CL=0.20-0.75). Childhood vaccinations' studied did not increase the risk of Kawasaki disease; conversely, vaccination was associated with a transient decrease in Kawasaki disease incidence. Verifying and understanding this potential protective effect could yield clues to the underlying etiology of Kawasaki disease. Copyright © 2014. Published by Elsevier Ltd.

Do Vaccines Cause Autism? Is it OK to Skip Certain Vaccines? Get the facts

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... Lifestyle Infant and toddler health Do vaccines cause autism? Is it OK to skip certain vaccines? Get ... their potentially serious complications. Vaccines do not cause autism. Despite much controversy on the topic, researchers haven' ...

APC targeting enhances immunogenicity of a novel multistage Fc-fusion tuberculosis vaccine in mice.

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Soleimanpour, Saman; Farsiani, Hadi; Mosavat, Arman; Ghazvini, Kiarash; Eydgahi, Mohammad Reza Akbari; Sankian, Mojtaba; Sadeghian, Hamid; Meshkat, Zahra; Rezaee, Seyed Abdolrahim

2015-12-01

Numerous studies have demonstrated that targeting immunogens to FcγR on antigen-presenting cells (APCs) can selectively uptake and increase cellular immunity in vitro and in vivo. Therefore, the present study was conducted to evaluate immunogenicity of a novel multistage tuberculosis vaccine, a combination of an early and a dormant immunogenic protein, ESAT6 and HspX, fused to Fcγ2a fragment of mouse IgG2a to target all forms of tuberculosis. Codon-optimized genes consisting of ESAT6, a linker, and HspX fused either to mouse Fcγ2a (ESAT6:HspX:mFcγ2a) or 6× His-tag (ESAT6:HspX:His) were synthesized. The resulting proteins were then produced in Pichia pastoris. The fusion proteins were separately emulsified in dimethyldioctadecylammonium bromide(DDA)-trehalose-6,6-dibehenate(TDB) adjuvant, and their immunogenicity with and without bacille Calmette-Guérin (BCG) was assessed in C57BL/6 mice. Th1, Th2, Th17, and T-reg cytokine patterns were evaluated using the ELISA method. Both multistage vaccines induced very strong IL-12 and IFN-γ secretion from splenic cells; the Fc-tagged subunit vaccine induced a more effective Th1 immune response (IFN-γ, 910 pg/mL, and IL-12, 854 pg/mL) with a very low increase in IL-17 (∼0.1 pg/mL) and IL-4 (37 pg/mL) and a mild increase in TGF-β (543 pg/mL) compared to the BCG or ESAT6:HspX:His primed and boosted groups. The production of IFN-γ to ESAT6:HspX:Fcγ2a was very consistent and showed an increasing trend for IL-12 compared to the BCG or ESAT6:HspX:His primed and boosted groups. Fcγ2a used as a delivery vehicle supported the idea of selective uptake, inducing cross-presentation and forming a proper anti-tuberculosis response in context of Th1/Th2 and Th17/T-reg balances, which is important for protection and prevention of damage.

Monitoring the impact of HPV vaccine in males—Considerations and challenges

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Julia M.L. Brotherton

2016-12-01

Full Text Available In this article, we examine the issues involved if national or sub-national programs are considering extending post HPV vaccine introduction monitoring to include males. Vaccination programs are now being extended to include males in some countries, in order to improve population level HPV infection control and to directly prevent HPV-related disease in males such as anogenital warts and anal cancers. Coverage and adverse events surveillance are essential components of post-vaccination monitoring. Monitoring the impact of vaccination on HPV infection and disease in men raises some similar challenges to monitoring in females, such as the long time frame until cancer outcomes, and also different ones given that genital specimens suitable for monitoring HPV prevalence are not routinely collected for other diagnostic or screening purposes in males. Thus, dedicated surveillance strategies must be designed; the framework of these may be country-specific, dependent upon the male population that is offered vaccination, the health care infrastructure and existing models of disease surveillance such as STI networks. The primary objective of any male HPV surveillance program will be to document changes in the prevalence of HPV infection and disease due to vaccine targeted HPV types occurring post vaccination. The full spectrum of outcomes to be considered for inclusion in any surveillance plan includes HPV prevalence monitoring, anogenital warts, potentially pre-cancerous lesions such as anal squamous intraepithelial lesions (SIL, and cancers. Ideally, a combination of short term and long term outcome measures would be included. Surveillance over time in specific targeted populations of men who have sex with men and HIV-infected men (populations at high risk for HPV infection and associated disease could be an efficient use of resources to demonstrate impact. Keywords: Human papillomavirus, Males, Disease surveillance, Vaccine effectiveness

The Potential Value of Clostridium difficile Vaccine: An Economic Computer Simulation Model

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Lee, Bruce Y.; Popovich, Michael J.; Tian, Ye; Bailey, Rachel R.; Ufberg, Paul J.; Wiringa, Ann E.; Muder, Robert R.

2010-01-01

Efforts are currently underway to develop a vaccine against Clostridium difficile infection (CDI). We developed two decision analytic Monte Carlo computer simulation models: (1) an Initial Prevention Model depicting the decision whether to administer C. difficile vaccine to patients at-risk for CDI and (2) a Recurrence Prevention Model depicting the decision whether to administer C. difficile vaccine to prevent CDI recurrence. Our results suggest that a C. difficile vaccine could be cost-effective over a wide range of C. difficile risk, vaccine costs, and vaccine efficacies especially when being used post-CDI treatment to prevent recurrent disease. PMID:20541582

Monitoring What Governments “Give for” and “Spend on” Vaccine Procurement: Vaccine Procurement Assistance and Vaccine Procurement Baseline

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Nelson, E. A. S.; Bloom, David E.; Mahoney, Richard T.

2014-01-01

Background The Global Vaccine Action Plan will require, inter alia, the mobilization of financial resources from donors and national governments – both rich and poor. Vaccine Procurement Assistance (VPA) and Vaccine Procurement Baseline (VPB) are two metrics that could measure government performance and track resources in this arena. VPA is proposed as a new subcategory of Official Development Assistance (ODA) given for the procurement of vaccines and VPB is a previously suggested measure of the share of Gross Domestic Product (GDP) that governments spend on their own vaccine procurement. Objective To determine realistic targets for VPA and VPB. Methods Organization for Economic Co-Operation and Development (OECD) and World Bank data for 2009 were analyzed to determine the proportions of bilateral ODA from the 23 Development Assistance Committee (DAC) countries disbursed (as % of GDP in current US$) for infectious disease control. DAC country contributions to the GAVI Alliance for 2009 were assessed as a measure of multilateral donor support for vaccines and immunization programs. Findings In 2009, total DAC bilateral ODA was 0.16% of global GDP and 0.25% of DAC GDP. As a percentage of GDP, Norway (0.013%) and United Kingdom (0.0085%) disbursed the greatest proportion of bilateral ODA for infectious disease control, and Norway (0.024%) and Canada (0.008%) made the greatest contributions to the GAVI Alliance. In 2009 0.02% of DAC GDP was US$7.61 billion and 0.02% of the GDP of the poorest 117 countries was US$2.88 billion. Conclusions Adopting 0.02% GDP as minimum targets for both VPA and VPB is based on realistic estimates of what both developed and developing countries should spend, and can afford to spend, to jointly ensure procurement of vaccines recommended by national and global bodies. New OECD purpose codes are needed to specifically track ODA disbursed for a) vaccine procurement; and b) immunization programs. PMID:24586899

Varicella zoster vaccines and their implications for development of HSV vaccines

International Nuclear Information System (INIS)

Gershon, Anne A.

2013-01-01

Live attenuated vaccines to prevent varicella and zoster have been available in the US for the past 17 years, with a resultant dramatic decrease in varicella incidence and a predicted future decrease in the incidence of zoster. The pathogenesis and immune responses to varicella zoster virus (VZV) as well as the safety and effectiveness of VZV vaccines are reviewed. The lack of sterilizing immunity provided by VZV vaccines has not prevented them from being safe and effective. Virological and pathological information concerning parallels and differences between VZV and herpes simplex virus (HSV) are highlighted. Although VZV and HSV are distinct pathogens, they appear to have similarities in target organs and immunity that provide an expectation of a high likelihood for the success of vaccination against HSV, and predicted to be similar to that of VZV.

Varicella zoster vaccines and their implications for development of HSV vaccines

Energy Technology Data Exchange (ETDEWEB)

Gershon, Anne A., E-mail: aag1@columbia.edu [Department of Pediatrics, Columbia University College of Physicians and Surgeons, 620W. 168th Street, NY, NY 10032 (United States)

2013-01-05

Live attenuated vaccines to prevent varicella and zoster have been available in the US for the past 17 years, with a resultant dramatic decrease in varicella incidence and a predicted future decrease in the incidence of zoster. The pathogenesis and immune responses to varicella zoster virus (VZV) as well as the safety and effectiveness of VZV vaccines are reviewed. The lack of sterilizing immunity provided by VZV vaccines has not prevented them from being safe and effective. Virological and pathological information concerning parallels and differences between VZV and herpes simplex virus (HSV) are highlighted. Although VZV and HSV are distinct pathogens, they appear to have similarities in target organs and immunity that provide an expectation of a high likelihood for the success of vaccination against HSV, and predicted to be similar to that of VZV.

Motivations and concerns about adolescent tuberculosis vaccine trial participation in rural Uganda: a qualitative study.

Science.gov (United States)

Buregyeya, Esther; Kulane, Asli; Kiguli, Juliet; Musoke, Phillipa; Mayanja, Harriet; Mitchell, Ellen Maeve Hanlon

2015-01-01

Research is being carried out to develop and test new potentially more effective tuberculosis vaccines. Among the vaccines being developed are those that target adolescents. This study explored the stakeholders' perceptions about adolescent participation in a hypothetical tuberculosis vaccine trial in Ugandan adolescents. Focus group discussions with adolescents, parents of infants and adolescents, and key informant interviews with community leaders and traditional healers were conducted. The majority of the respondents expressed potential willingness to allow their children participate in a tuberculosis vaccine trial. Main motivations for potential participation would be being able to learn about health-related issues. Hesitations included the notion that trial participation would distract the youths from their studies, fear of possible side effects of an investigational product, and potential for being sexually exploited by researchers. In addition, bad experiences from participation in previous research and doubts about the importance of research were mentioned. Suggested ways to motivate participation included: improved clarity on study purpose, risks, benefits and better scheduling of study procedures to minimize disruption to participants' academic schedules. Findings from this study suggest that the community is open to potential participation of adolescents in a tuberculosis vaccine trial. However, there is a need to communicate more effectively with the community about the purpose of the trial and its effects, including safety data, in a low-literacy, readily understood format. This raises a challenge to researchers, who cannot know all the potential effects of a trial product before it is tested.

Vaccines against invasive Salmonella disease

Science.gov (United States)

MacLennan, Calman A; Martin, Laura B; Micoli, Francesca

2014-01-01

Though primarily enteric pathogens, Salmonellae are responsible for a considerable yet under-appreciated global burden of invasive disease. In South and South-East Asia, this manifests as enteric fever caused by serovars Typhi and Paratyphi A. In sub-Saharan Africa, a similar disease burden results from invasive nontyphoidal Salmonellae, principally serovars Typhimurium and Enteritidis. The existing Ty21a live-attenuated and Vi capsular polysaccharide vaccines target S. Typhi and are not effective in young children where the burden of invasive Salmonella disease is highest. After years of lack of investment in new Salmonella vaccines, recent times have seen increased interest in the area led by emerging-market manufacturers, global health vaccine institutes and academic partners. New glycoconjugate vaccines against S. Typhi are becoming available with similar vaccines against other invasive serovars in development. With other new vaccines under investigation, including live-attenuated, protein-based and GMMA vaccines, now is an exciting time for the Salmonella vaccine field. PMID:24804797

A Randomized Controlled Trial to Evaluate a Potential Hepatitis B Booster Vaccination Strategy Using Combined Hepatitis A and B Vaccine.

Science.gov (United States)

Li, Fangjun; Hu, Yuansheng; Zhou, Youming; Chen, Lixin; Xia, Wei; Song, Yufei; Tan, Zhengliang; Gao, Lidong; Yang, Zhong; Zeng, Gang; Han, Xing; Li, Junhua; Li, Jing

2017-05-01

Booster doses could play a major role in no responders or low responders to primary hepatitis B (HB) vaccine. Planed time point for hepatitis A vaccination in China provides a good opportunity to carry out HB booster dose by using combined hepatitis A and B vaccine. A randomized, double-blinded clinical trial was conducted to compare the immunogenicity and safety of toddlers 18-24 months of age receiving 3 different vaccination regimens: 2 doses of inactivated hepatitis A vaccine (group 1), 1 dose of inactivated hepatitis A vaccine plus 1 dose of combined hepatitis A and B vaccine (group 2) or 2 doses of combined hepatitis A and B vaccine (group 3). All 3 groups showed 100% seroprotection for antihepatitis A virus antibody after vaccination. Seroprotection rate for anti-HB antibody before vaccination ranged from 79.5% to 92.9% in the 3 groups. After second inoculation, anti-HBs seroprotection increased from 92.9% to 100% in group 2 with postvaccination geometric mean concentration (GMC) of 2258.3 mIU/mL and from 79.5% to 98.9% in group 3 with postvaccination GMC of 2055.3 mIU/mL. The adverse events were not statistically different among groups (P = 0.345). Combined hepatitis A and B vaccine could stimulate high level of both antihepatitis A virus and anti-HBs antibodies and not increase adverse events, providing a new choice for HB booster.

Black mother's intention to vaccinate daughters against HPV: A mixed methods approach to identify opportunities for targeted communication.

Science.gov (United States)

Cunningham-Erves, Jennifer; Forbes, Laura; Ivankova, Nataliya; Mayo-Gamble, Tilicia; Kelly-Taylor, Kendria; Deakings, Jason

2018-03-24

The cervical cancer disparity continues to exist and has widened between Black and non-Hispanic White women. Human Papillomavirus (HPV) vaccines could potentially reduce this disparity, yet remain underused among Black female adolescents. We investigated psychosocial and cultural factors associated with Black mothers' intentions to vaccinate their daughters against HPV, and explored views toward a HPV vaccine mandate. In this quantitative dominant, mixed methods study, cross sectional surveys (n=237) and follow-up semi-structured interviews (n=9) were conducted with Black mothers of daughters. A 2-step logistic regression determined factors associated with Black mothers' intention. Thematic content analysis determined emerging themes. Perceived susceptibility (p=.044), perceived barriers (pHPV vaccination intentions. Follow-up interviews provided insight into factors influencing mothers' intentions. Mothers with low intentions did not perceive their daughter to be currently sexually active or in near future, thus, not at HPV risk. Pediatricians were identified as the most influential person on maternal decision-making if there was a pre-existing relationship. However, many mothers had not received a pediatricians' recommendation for their daughters. Barriers influencing mother's decision-making include knowledge, daughters' age, and mistrust in pharmaceutical companies and physicians. Mothers were not in favor of the HPV vaccine mandate. Findings demonstrate the need to develop and evaluate physician-led interventions on HPV and vaccine importance, and engage these mothers in intervention development to build trust between physicians, researchers, and Black mothers to improve HPV vaccine uptake in Black female adolescents. Published by Elsevier Inc.

First outbreak response using an oral cholera vaccine in Africa: vaccine coverage, acceptability and surveillance of adverse events, Guinea, 2012.

Directory of Open Access Journals (Sweden)

Francisco J Luquero

Full Text Available BACKGROUND: Despite World Health Organization (WHO prequalification of two safe and effective oral cholera vaccines (OCV, concerns about the acceptability, potential diversion of resources, cost and feasibility of implementing timely campaigns has discouraged their use. In 2012, the Ministry of Health of Guinea, with the support of Médecins Sans Frontières organized the first mass vaccination campaign using a two-dose OCV (Shanchol as an additional control measure to respond to the on-going nationwide epidemic. Overall, 316,250 vaccines were delivered. Here, we present the results of vaccination coverage, acceptability and surveillance of adverse events. METHODOLOGY/PRINCIPAL FINDINGS: We performed a cross-sectional cluster survey and implemented adverse event surveillance. The study population included individuals older than 12 months, eligible for vaccination, and residing in the areas targeted for vaccination (Forécariah and Boffa, Guinea. Data sources were household interviews with verification by vaccination card and notifications of adverse events from surveillance at vaccination posts and health centres. In total 5,248 people were included in the survey, 3,993 in Boffa and 1,255 in Forécariah. Overall, 89.4% [95%CI:86.4-91.8%] and 87.7% [95%CI:84.2-90.6%] were vaccinated during the first round and 79.8% [95%CI:75.6-83.4%] and 82.9% [95%CI:76.6-87.7%] during the second round in Boffa and Forécariah respectively. The two dose vaccine coverage (including card and oral reporting was 75.8% [95%CI: 71.2-75.9%] in Boffa and 75.9% [95%CI: 69.8-80.9%] in Forécariah respectively. Vaccination coverage was higher in children. The main reason for non-vaccination was absence. No severe adverse events were notified. CONCLUSIONS/SIGNIFICANCE: The well-accepted mass vaccination campaign reached high coverage in a remote area with a mobile population. Although OCV should not be foreseen as the long-term solution for global cholera control, they

The role of vaccines and vaccine decision-making to achieve the goals of the Grand Convergence in public health.

Science.gov (United States)

Kaslow, David C; Kalil, Jorge; Bloom, David; Breghi, Gianluca; Colucci, Anna Maria; De Gregorio, Ennio; Madhavan, Guru; Meier, Genevieve; Seabrook, Richard; Xu, Xiaoning

2017-01-20

On 17 and 18 July 2015, a meeting in Siena jointly sponsored by ADITEC and GlaxoSmithKline (GSK) was held to review the goals of the Global Health 2035 Grand Convergence, to discuss current vaccine evaluation methods, and to determine the feasibility of reaching consensus on an assessment framework for comprehensively and accurately capturing the full benefits of vaccines. Through lectures and workshops, participants reached a consensus that Multi-Criteria-Decision-Analysis is a method suited to systematically account for the many variables needed to evaluate the broad benefits of vaccination, which include not only health system savings, but also societal benefits, including benefits to the family and increased productivity. Participants also agreed on a set of "core values" to be used in future assessments of vaccines for development and introduction. These values include measures of vaccine efficacy and safety, incident cases prevented per year, the results of cost-benefit analyses, preventable mortality, and the severity of the target disease. Agreement on this set of core assessment parameters has the potential to increase alignment between manufacturers, public health agencies, non-governmental organizations (NGOs), and policy makers (see Global Health 2035 Mission Grand Convergence [1]). The following sections capture the deliberations of a workshop (Working Group 4) chartered to: (1) review the list of 24 parameters selected from SMART vaccines (see the companion papers by Timmis et al. and Madhavan et al., respectively) to determine which represent factors (see Table 1) that should be taken into account when evaluating the role of vaccines in maximizing the success of the Global Health 2035 Grand Convergence; (2) develop 3-5 "core values" that should be taken into account when evaluating vaccines at various stages of development; and (3) determine how vaccines can best contribute to the Global Health 2035 Grand Convergence effort. Copyright © 2016.

Characterization and vaccine potential of Fasciola gigantica saposin-like protein 1 (SAP-1).

Science.gov (United States)

Kueakhai, Pornanan; Changklungmoa, Narin; Waseewiwat, Pinkamon; Thanasinpaiboon, Thanaporn; Cheukamud, Werachon; Chaichanasak, Pannigan; Sobhon, Prasert

2017-01-15

The recombinant Fasciola gigantica Saposin-like protien-1 (rFgSAP-1) was cloned by polymerase chain reaction (PCR) from NEJ cDNA, expressed in Escherichia coli BL21 (DE3) and used for production of a polyclonal antibody in rabbits (anti-rFgSAP-1). By immunoblotting and immunohistochemistry, rabbit IgG anti-rFgSAP-1 reacted with rFgSAP-1 at a molecular weight 12kDa, but not with rFgSAP-2. The rFgSAP-1 reacted with antisera from mouse infected with F. gigantica metacercariae collected at 2, 4, and 6 weeks after infection. The FgSAP-1 protein was expressed at a high level in the caecal epithelium of metacercariae and NEJs. The vaccination was performed in Imprinting Control Region (ICR) mice (n=10) by subcutaneous injection with 50μg of rFgSAP-1 combined with Alum adjuvant. Two weeks after the second boost, mice were infected with 15 metacercariae per mouse by the oral route. The percents protection of rFgSAP-1 vaccine were estimated to be 73.2% and 74.3% when compared with non vaccinated-infected and adjuvant-infected controls, respectively. The levels of IgG1 and IgG2a specific to rFgSAP-1 in the immune sera, which are indicative of Th2 and Th1 immune responses, were inversely and significantly correlated with the numbers of worm recoveries. The rFgSAP-1-vaccinated mice showed significantly reduced levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and liver damage. These indicated that rFgSAP-1 has strong potential as a vaccine candidate against F. gigantica, whose efficacy will be studied further in large economic animals including cattle, sheep, and goat. Copyright © 2016 Elsevier B.V. All rights reserved.

Proteasomal targeting and minigene repetition improve cell-surface presentation of a transfected, modified melanoma tumour antigen

DEFF Research Database (Denmark)

Rasmussen, A B; Zocca, M-B; Bonefeld, C M

2004-01-01

Melanoma antigen recognized by T cell 1 (MART-1) is regarded as a candidate peptide for vaccination against malignant melanoma, and it is of importance to develop strategies to improve the vaccine-elicited T-cell activation towards MART-1. T-cell activation is, among other determinants, dependent...... on the density of specific major histocompatibility complex-peptide complexes on the surface of the antigen-presenting cell. In this study, we explored the cell-surface presentation of a substituted MART-1 peptide encoded by transfected minigenes. We investigated the potential of proteasomal targeting compared...... to non-proteasomal targeting of the epitope to increase its cell-surface presentation. Furthermore, we explored the potential of incorporating multiple minigenes instead of one to increase cell-surface presentation. We show that both proteasomal targeting and repetition of the minigene increase cell...

Potential public health impact of RTS,S malaria candidate vaccine in sub-Saharan Africa: a modelling study.

Science.gov (United States)

Sauboin, Christophe J; Van Bellinghen, Laure-Anne; Van De Velde, Nicolas; Van Vlaenderen, Ilse

2015-12-23

Adding malaria vaccination to existing interventions could help to reduce the health burden due to malaria. This study modelled the potential public health impact of the RTS,S candidate malaria vaccine in 42 malaria-endemic countries in sub-Saharan Africa. An individual-based Markov cohort model was constructed with three categories of malaria transmission intensity and six successive malaria immunity levels. The cycle time was 5 days. Vaccination was assumed to reduce the risk of infection, with no other effects. Vaccine efficacy was assumed to wane exponentially over time. Malaria incidence and vaccine efficacy data were taken from a Phase III trial of the RTS,S vaccine with 18 months of follow-up (NCT00866619). The model was calibrated to reproduce the malaria incidence in the control arm of the trial in each transmission category and published age distribution data. Individual-level heterogeneity in malaria exposure and vaccine protection was accounted for. Parameter uncertainty and variability were captured by using stochastic model transitions. The model followed a cohort from birth to 10 years of age without malaria vaccination, or with RTS,S malaria vaccination administered at age 6, 10 and 14 weeks or at age 6, 7-and-a-half and 9 months. Median and 95% confidence intervals were calculated for the number of clinical malaria cases, severe cases, malaria hospitalizations and malaria deaths expected to be averted by each vaccination strategy. Univariate sensitivity analysis was conducted by varying the values of key input parameters. Vaccination assuming the coverage of diphtheria-tetanus-pertussis (DTP3) at age 6, 10 and 14 weeks is estimated to avert over five million clinical malaria cases, 119,000 severe malaria cases, 98,600 malaria hospitalizations and 31,000 malaria deaths in the 42 countries over the 10-year period. Vaccination at age 6, 7-and-a-half and 9 months with 75% of DTP3 coverage is estimated to avert almost 12.5 million clinical malaria cases

The impact of making vaccines thermostable in Niger's vaccine supply chain.

Science.gov (United States)

Lee, Bruce Y; Cakouros, Brigid E; Assi, Tina-Marie; Connor, Diana L; Welling, Joel; Kone, Souleymane; Djibo, Ali; Wateska, Angela R; Pierre, Lionel; Brown, Shawn T

2012-08-17

Determine the effects on the vaccine cold chain of making different types of World Health Organization (WHO) Expanded Program on Immunizations (EPI) vaccines thermostable. Utilizing a detailed computational, discrete-event simulation model of the Niger vaccine supply chain, we simulated the impact of making different combinations of the six current EPI vaccines thermostable. Making any EPI vaccine thermostable relieved existing supply chain bottlenecks (especially at the lowest levels), increased vaccine availability of all EPI vaccines, and decreased cold storage and transport capacity utilization. By far, the most substantial impact came from making the pentavalent vaccine thermostable, increasing its own vaccine availability from 87% to 97% and the vaccine availabilities of all other remaining non-thermostable EPI vaccines to over 93%. By contrast, making each of the other vaccines thermostable had considerably less effect on the remaining vaccines, failing to increase the vaccine availabilities of other vaccines to more than 89%. Making tetanus toxoid vaccine along with the pentavalent thermostable further increased the vaccine availability of all EPI vaccines by at least 1-2%. Our study shows the potential benefits of making any of Niger's EPI vaccines thermostable and therefore supports further development of thermostable vaccines. Eliminating the need for refrigerators and freezers should not necessarily be the only benefit and goal of vaccine thermostability. Rather, making even a single vaccine (or some subset of the vaccines) thermostable could free up significant cold storage space for other vaccines, and thereby help alleviate supply chain bottlenecks that occur throughout the world. Copyright © 2012 Elsevier Ltd. All rights reserved.

Vaccination in food allergic patients

African Journals Online (AJOL)

Most people do not react to vaccination and the incidence of vaccine anaphylaxis is estimated to be <1/million for all vaccines.[1] Most anaphylactic reactions occur in non-food allergic children. It is strongly recommended that anyone admin- istering vaccines has resuscitation equipment available to manage potential ...

Ethical considerations for vaccination programmes in acute humanitarian emergencies

Science.gov (United States)

Hardie, Kate; Selgelid, Michael J; Waldman, Ronald J; Strebel, Peter; Rees, Helen; Durrheim, David N

2013-01-01

Abstract Humanitarian emergencies result in a breakdown of critical health-care services and often make vulnerable communities dependent on external agencies for care. In resource-constrained settings, this may occur against a backdrop of extreme poverty, malnutrition, insecurity, low literacy and poor infrastructure. Under these circumstances, providing food, water and shelter and limiting communicable disease outbreaks become primary concerns. Where effective and safe vaccines are available to mitigate the risk of disease outbreaks, their potential deployment is a key consideration in meeting emergency health needs. Ethical considerations are crucial when deciding on vaccine deployment. Allocation of vaccines in short supply, target groups, delivery strategies, surveillance and research during acute humanitarian emergencies all involve ethical considerations that often arise from the tension between individual and common good. The authors lay out the ethical issues that policy-makers need to bear in mind when considering the deployment of mass vaccination during humanitarian emergencies, including beneficence (duty of care and the rule of rescue), non-maleficence, autonomy and consent, and distributive and procedural justice. PMID:23599553

Proof of principle for epitope-focused vaccine design

Science.gov (United States)

Correia, Bruno E.; Bates, John T.; Loomis, Rebecca J.; Baneyx, Gretchen; Carrico, Chris; Jardine, Joseph G.; Rupert, Peter; Correnti, Colin; Kalyuzhniy, Oleksandr; Vittal, Vinayak; Connell, Mary J.; Stevens, Eric; Schroeter, Alexandria; Chen, Man; MacPherson, Skye; Serra, Andreia M.; Adachi, Yumiko; Holmes, Margaret A.; Li, Yuxing; Klevit, Rachel E.; Graham, Barney S.; Wyatt, Richard T.; Baker, David; Strong, Roland K.; Crowe, James E.; Johnson, Philip R.; Schief, William R.

2014-03-01

Vaccines prevent infectious disease largely by inducing protective neutralizing antibodies against vulnerable epitopes. Several major pathogens have resisted traditional vaccine development, although vulnerable epitopes targeted by neutralizing antibodies have been identified for several such cases. Hence, new vaccine design methods to induce epitope-specific neutralizing antibodies are needed. Here we show, with a neutralization epitope from respiratory syncytial virus, that computational protein design can generate small, thermally and conformationally stable protein scaffolds that accurately mimic the viral epitope structure and induce potent neutralizing antibodies. These scaffolds represent promising leads for the research and development of a human respiratory syncytial virus vaccine needed to protect infants, young children and the elderly. More generally, the results provide proof of principle for epitope-focused and scaffold-based vaccine design, and encourage the evaluation and further development of these strategies for a variety of other vaccine targets, including antigenically highly variable pathogens such as human immunodeficiency virus and influenza.

Optimal serotype compositions for Pneumococcal conjugate vaccination under serotype replacement.

Science.gov (United States)

Nurhonen, Markku; Auranen, Kari

2014-02-01

Pneumococcal conjugate vaccination has proved highly effective in eliminating vaccine-type pneumococcal carriage and disease. However, the potential adverse effects of serotype replacement remain a major concern when implementing routine childhood pneumococcal conjugate vaccination programmes. Applying a concise predictive model, we present a ready-to-use quantitative tool to investigate the implications of serotype replacement on the net effectiveness of vaccination against invasive pneumococcal disease (IPD) and to guide in the selection of optimal vaccine serotype compositions. We utilise pre-vaccination data on pneumococcal carriage and IPD and assume partial or complete elimination of vaccine-type carriage, its replacement by non-vaccine-type carriage, and stable case-to-carrier ratios (probability of IPD per carriage episode). The model predicts that the post-vaccination IPD incidences in Finland for currently available vaccine serotype compositions can eventually decrease among the target age group of children replacement through herd effects, the decrease among the older population is predicted to be much less (20-40%). We introduce a sequential algorithm for the search of optimal serotype compositions and assess the robustness of inferences to uncertainties in data and assumptions about carriage and IPD. The optimal serotype composition depends on the age group of interest and some serotypes may be highly beneficial vaccine types in one age category (e.g. 6B in children), while being disadvantageous in another. The net effectiveness will be improved only if the added serotype has a higher case-to-carrier ratio than the average case-to-carrier ratio of the current non-vaccine types and the degree of improvement in effectiveness depends on the carriage incidence of the serotype. The serotype compositions of currently available pneumococcal vaccines are not optimal and the effectiveness of vaccination in the population at large could be improved by including

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

Directory of Open Access Journals (Sweden)

Farzad Khademi

2018-02-01

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

Prediction of potential drug targets based on simple sequence properties

Directory of Open Access Journals (Sweden)

Lai Luhua

2007-09-01

Full Text Available Abstract Background During the past decades, research and development in drug discovery have attracted much attention and efforts. However, only 324 drug targets are known for clinical drugs up to now. Identifying potential drug targets is the first step in the process of modern drug discovery for developing novel therapeutic agents. Therefore, the identification and validation of new and effective drug targets are of great value for drug discovery in both academia and pharmaceutical industry. If a protein can be predicted in advance for its potential application as a drug target, the drug discovery process targeting this protein will be greatly speeded up. In the current study, based on the properties of known drug targets, we have developed a sequence-based drug target prediction method for fast identification of novel drug targets. Results Based on simple physicochemical properties extracted from protein sequences of known drug targets, several support vector machine models have been constructed in this study. The best model can distinguish currently known drug targets from non drug targets at an accuracy of 84%. Using this model, potential protein drug targets of human origin from Swiss-Prot were predicted, some of which have already attracted much attention as potential drug targets in pharmaceutical research. Conclusion We have developed a drug target prediction method based solely on protein sequence information without the knowledge of family/domain annotation, or the protein 3D structure. This method can be applied in novel drug target identification and validation, as well as genome scale drug target predictions.

User-Centered Design for Developing Interventions to Improve Clinician Recommendation of Human Papillomavirus Vaccination.

Science.gov (United States)

Henninger, Michelle L; Mcmullen, Carmit K; Firemark, Alison J; Naleway, Allison L; Henrikson, Nora B; Turcotte, Joseph A

2017-01-01

Human papillomavirus (HPV) is the most common sexually transmitted infection in the US and is associated with multiple types of cancer. Although effective HPV vaccines have been available since 2006, coverage rates in the US remain much lower than with other adolescent vaccinations. Prior research has shown that a strong recommendation from a clinician is a critical determinant in HPV vaccine uptake and coverage. However, few published studies to date have specifically addressed the issue of helping clinicians communicate more effectively with their patients about the HPV vaccine. To develop one or more novel interventions for helping clinicians make strong and effective recommendations for HPV vaccination. Using principles of user-centered design, we conducted qualitative interviews, interviews with persons from analogous industries, and a data synthesis workshop with multiple stakeholders. Five potential intervention strategies targeted at health care clinicians, youth, and their parents were developed. The two most popular choices to pursue were a values-based communication strategy and a puberty education workbook. User-centered design is a useful strategy for developing potential interventions to improve the rate and success of clinicians recommending the HPV vaccine. Further research is needed to test the effectiveness and acceptability of these interventions in clinical settings.

A New Decade of Vaccines

LENUS (Irish Health Repository)

Murphy, JFA

2011-09-01

The call for a new decade of vaccines was made in December 2010. The aims are to secure the further discovery, development and delivery of vaccination. The first challenge is the acquisition of funds for the research and development of 20 new vaccines1. The Gates Foundation has pledged $10 billion for this venture. The other major players are WHO, UNICEF and the US National Institute of Allergy and Infectious Diseases. The top priorities are TB, AIDS and Malaria. It is hoped that a Malaria vaccine will available in 3 years. The ambitious target of saving the lives of over 7 million children has been set. The programme must also address the need for vaccines in insulin dependent diabetes, cancers and degenerative diseases2.

Potential overestimation of HPV vaccine impact due to unmasking of non-vaccine types: quantification using a multi-type mathematical model.

Science.gov (United States)

Choi, Yoon Hong; Chapman, Ruth; Gay, Nigel; Jit, Mark

2012-05-14

Estimates of human papillomavirus (HPV) vaccine impact in clinical trials and modelling studies rely on DNA tests of cytology or biopsy specimens to determine the HPV type responsible for a cervical lesion. DNA of several oncogenic HPV types may be detectable in a specimen. However, only one type may be responsible for a particular cervical lesion. Misattribution of the causal HPV type for a particular abnormality may give rise to an apparent increase in disease due to non-vaccine HPV types following vaccination ("unmasking"). To investigate the existence and magnitude of unmasking, we analysed data from residual cytology and biopsy specimens in English women aged 20-64 years old using a stochastic type-specific individual-based model of HPV infection, progression and disease. The model parameters were calibrated to data on the prevalence of HPV DNA and cytological lesion of different grades, and used to assign causal HPV types to cervical lesions. The difference between the prevalence of all disease due to non-vaccine HPV types, and disease due to non-vaccine HPV types in the absence of vaccine HPV types, was then estimated. There could be an apparent maximum increase of 3-10% in long-term cervical cancer incidence due to non-vaccine HPV types following vaccination. Unmasking may be an important phenomenon in HPV post-vaccination epidemiology, in the same way that has been observed following pneumococcal conjugate vaccination. Copyright © 2012 Elsevier Ltd. All rights reserved.

The epidemiological impact of childhood influenza vaccination using live-attenuated influenza vaccine (LAIV) in Germany: predictions of a simulation study

Science.gov (United States)

2014-01-01

Background Routine annual influenza vaccination is primarily recommended for all persons aged 60 and above and for people with underlying chronic conditions in Germany. Other countries have already adopted additional childhood influenza immunisation programmes. The objective of this study is to determine the potential epidemiological impact of implementing paediatric influenza vaccination using intranasally administered live-attenuated influenza vaccine (LAIV) in Germany. Methods A deterministic age-structured model is used to simulate the population-level impact of different vaccination strategies on the transmission dynamics of seasonal influenza in Germany. In our base-case analysis, we estimate the effects of adding a LAIV-based immunisation programme targeting children 2 to 17 years of age to the existing influenza vaccination policy. The data used in the model is based on published evidence complemented by expert opinion. Results In our model, additional vaccination of children 2 to 17 years of age with LAIV leads to the prevention of 23.9 million influenza infections and nearly 16 million symptomatic influenza cases within 10 years. This reduction in burden of disease is not restricted to children. About one third of all adult cases can indirectly be prevented by LAIV immunisation of children. Conclusions Our results demonstrate that vaccinating children 2–17 years of age is likely associated with a significant reduction in the burden of paediatric influenza. Furthermore, annual routine childhood vaccination against seasonal influenza is expected to decrease the incidence of influenza among adults and older people due to indirect effects of herd protection. In summary, our model provides data supporting the introduction of a paediatric influenza immunisation programme in Germany. PMID:24450996

Advocating zoster vaccination in a community pharmacy through use of personal selling.

Science.gov (United States)

Bryan, Amy R; Liu, Yifei; Kuehl, Peggy G

2013-01-01

To evaluate whether the use of personal selling, in combination with other promotional techniques, could improve patient commitment to receive the targeted intervention of herpes zoster vaccine (Zostavax-Merck). Two locally owned grocery store chain pharmacies in the Kansas City, MO, metropolitan area (Price Chopper Pharmacy 11 [PC11] and Price Chopper Pharmacy 36 [PC36]). Price Chopper Pharmacy employs pharmacists who are able to administer vaccinations to patients within the dispensing workflow. Passive signage promoting zoster vaccine was placed at both PC11 and PC36. Personal selling by pharmacy staff to targeted patients was implemented at PC36, where patients were encouraged to receive zoster vaccine at prescription pick up and/or by personalized letter. Primary measures included comparison of the number committing to receive zoster vaccine at either pharmacy, comparison of patient perceptions regarding each pharmacy's promotion of zoster vaccine, and pharmacy staff time spent identifying targeted patients and performing personal selling activities. 90 of 745 targeted patients (12.1%) at PC36 made commitments to receive zoster vaccine compared with 9 of 614 (1.5%) at PC11 (P < 0.001). The barrier of "Dr. hasn't told me I need it" was reduced for PC36 patients (P < 0.05). Patients receiving vaccination had a more favorable attitude toward receiving zoster vaccine than unvaccinated patients (P < 0.01). Among unvaccinated patients, those at PC36 had a more favorable attitude toward receiving zoster vaccine after interacting with a pharmacist (P < 0.05). Personal selling increased patient commitment to receiving a targeted intervention significantly. By using personal selling, pharmacists resolved barriers to immunization.

A qualitative analysis of the beliefs of Japanese anti-influenza vaccination website authors

Directory of Open Access Journals (Sweden)

Tsuyoshi Okuhara

2018-04-01

Full Text Available Background: Influenza vaccine coverage among the Japanese population is less than optimal. Anti-vaccination sentiment exists worldwide, and Japan is no exception. Anti-influenza vaccination activists argue on the internet that influenza vaccine has little or no efficacy and a high risk of side effects, and they warn that people should forgo vaccination. We conducted a qualitative analysis to explore beliefs underlying the messages of anti-influenza vaccination websites, by focusing on the perceived value these beliefs provide to those who hold them. Methods: We conducted online searches in January 2017 using two major Japanese search engines (Google Japan and Yahoo! Japan. Targeted websites were classified as “pro”, “anti”, or “neutral” depending on their claims. We applied a dual analytic approach—inductive thematic analysis and deductive interpretative analysis—to textual data of the anti websites. Results: Of the 113 anti websites, we identified two themes that correspond to beliefs: it is necessary to 1 protect others against risks and exploitation related to influenza vaccination, and 2 educate others about hidden truths and self-determination. Authors of anti websites ascribed two values (people's “safety” and one's own “self-esteem” to their beliefs. Discussion: Website authors may engage in anti-vaccination activities because they want to feel they are virtuous, saving people from harm caused by vaccination, and to boost their self-esteem, thinking “I am enlightening uninformed people.” The anti-vaccination beliefs of website authors were considered to be strong. In promoting vaccination, it would be better not to target outright vaccine refusers, such as the authors of anti-vaccination websites; it is preferable to target vaccine-hesitant people who are more amenable to changing their attitudes toward vaccination. We discuss possible means of promoting vaccination in that target population. Keywords

N-Terminal Plasmodium vivax Merozoite Surface Protein-1, a Potential Subunit for Malaria Vivax Vaccine

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Fernanda G. Versiani

2013-01-01

Full Text Available The human malaria is widely distributed in the Middle East, Asia, the western Pacific, and Central and South America. Plasmodium vivax started to have the attention of many researchers since it is causing diseases to millions of people and several reports of severe malaria cases have been noticed in the last few years. The lack of in vitro cultures for P. vivax represents a major delay in developing a functional malaria vaccine. One of the major candidates to antimalarial vaccine is the merozoite surface protein-1 (MSP1, which is expressed abundantly on the merozoite surface and capable of activating the host protective immunity. Studies have shown that MSP-1 possesses highly immunogenic fragments, capable of generating immune response and protection in natural infection in endemic regions. This paper shows humoral immune response to different proteins of PvMSP1 and the statement of N-terminal to be added to the list of potential candidates for malaria vivax vaccine.

Modeling HIV vaccines in Brazil: assessing the impact of a future HIV vaccine on reducing new infections, mortality and number of people receiving ARV.

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Maria Goretti P Fonseca

2010-07-01

Full Text Available 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.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.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.

Seasonal Influenza Vaccine Uptake in a Respiratory Outpatients Clinic

LENUS (Irish Health Repository)

Rossiter, A

2017-02-01

Influenza is an acute viral respiratory illness that continues to cause significant morbidity and mortality in Ireland. Despite well-established national and international guidelines1 and increased public awareness campaigns, vaccine uptake rates are well below target worldwide2. We performed an audit of influenza vaccine uptake at a Respiratory outpatient clinic in a tertiary referral centre. 54% (n=41) of patients received the annual vaccine, well below the target of 75% set by the European Centre for Disease Prevention and Control (ECDC).

Smallpox: clinical highlights and considerations for vaccination.

Directory of Open Access Journals (Sweden)

Mahoney M

2003-01-01

Full Text Available Smallpox virus has gained considerable attention as a potential bioterrorism agent. Recommendations for smallpox (vaccinia vaccination presume a low risk for use of smallpox as a terrorist biological agent and vaccination is currently recommended for selected groups of individuals such as health care workers, public health authorities, and emergency/rescue workers, among others. Information about adverse reactions to the smallpox vaccine is based upon studies completed during the 1950s and 1960s. The prevalence of various diseases has changed over the last four decades and new disease entities have been described during this period. The smallpox vaccination may be contra-indicated in many of these conditions. This has made pre-screening of potential vaccines necessary. It is believed that at present, the risks of vaccine-associated complications far outweigh the potential benefits of vaccination in the general population.

A qualitative study of HPV vaccine acceptability among health workers, teachers, parents, female pupils, and religious leaders in northwest Tanzania.

Science.gov (United States)

Remes, Pieter; Selestine, Veronica; Changalucha, John; Ross, David A; Wight, Daniel; de Sanjosé, Silvia; Kapiga, Saidi; Hayes, Richard J; Watson-Jones, Deborah

2012-08-03

As human papillomavirus (HPV) vaccines become available in developing countries, acceptability studies can help to better understand potential barriers and facilitators of HPV vaccination and guide immunisation programs. Prior to a cluster-randomised phase IV trial of HPV vaccination delivery strategies in Mwanza Region, Tanzania, qualitative research was conducted to assess attitudes and knowledge about cervical cancer and HPV, and acceptability of and potential barriers to HPV vaccination of Tanzanian primary schoolgirls. Semi-structured interviews (n=31) and group discussions (n=12) were conducted with a total of 169 respondents (parents, female pupils, teachers, health workers and religious leaders). While participants had heard of cancer in general, most respondents had no knowledge of cervical cancer, HPV, or HPV vaccines. Only health workers had heard of cervical cancer but very few knew its cause or had any awareness about HPV vaccines. After participants were provided with information about cervical cancer and HPV vaccination, the majority stated that they would support HPV vaccination of their daughter to protect them against cervical cancer. Opt-out consent for vaccination was considered acceptable. Most preferred age-based vaccination, saying this would target more girls before sexual debut than class-based vaccination. Potential side effects and infertility concerns were raised by 5/14 of participating male teachers. Reported acceptability of HPV vaccination amongst parents, teachers and other community members was high in this population. Respondents stressed the need to provide adequate information about the vaccine to parents, that also addresses side effects and infertility concerns. Copyright © 2012 Elsevier Ltd. All rights reserved.

An evaluation of the adverse reaction potential of three measles-mumps-rubella combination vaccines

Directory of Open Access Journals (Sweden)

Santos Boaventura Antônio dos

2002-01-01

Full Text Available Objective. To compare the incidence of adverse events following the administration of three commercially available measles-mumps-rubella (MMR combination vaccines. Methods. A randomized double-blind clinical trial was performed in 1996 that involved a total of 10 142 students 6-12 years of age in the state of Rio Grande do Sul, in Brazil. An MMR vaccine containing the Edmonston-Zagreb, Leningrad-Zagreb, and RA 27/3 strains ("vaccine A" was administered to 2 226 students (21.9% of the total; an MMR vaccine with the Moraten, Jeryl Lynn, and Wistar 27/3 strains ("vaccine B" was administered to 2 216 children (21.8%; and an MMR vaccine containing the Schwartz, Urabe AM-9, and Wistar 27/3 strains ("vaccine C" was given to 2 179 students (21.5%. A control group of 3 521 students (34.7% was not vaccinated. Both the vaccinated subjects and the control subjects were followed daily for 30 days to detect any clinical manifestations. Results. Adverse events were more frequent in the vaccinated children than in the control group (P < 0.01. In terms of causing parotitis, vaccine A had a relative risk (RR of 5.72 (95% confidence interval (CI = 3.11-10.54 when compared with vaccine B, and an RR of 2.33 (95% CI = 1.52-3.58 when compared with vaccine C. Vaccine A was also associated with an increased risk of lymphadenopathy when compared with vaccine B (RR = 3.11; 95% CI = 1.78-5.45 and with vaccine C (RR = 2.22; 95% CI = 1.35-3.66. Vaccine C was associated with an increased risk of parotitis when compared with vaccine B (RR = 2.46; 95% CI = 1.26-4.80. Three cases of aseptic meningitis were detected among the children in the study group, but only one case of vaccine-related aseptic meningitis was identified, among the children receiving vaccine A. Conclusions. The three MMR vaccines that we studied are associated with different risks of adverse events. We found vaccine A to cause more reactions than the two other vaccines, especially vaccine B. In addition

Assessment of the potential public health impact of Herpes Zoster vaccination in Germany.

Science.gov (United States)

Curran, Desmond; Van Oorschot, Desirée; Varghese, Lijoy; Oostvogels, Lidia; Mrkvan, Tomas; Colindres, Romulo; von Krempelhuber, Alfred; Anastassopoulou, Anastassia

2017-10-03

The aim of this study was to compare the public health impact of introducing 2 Herpes Zoster (HZ) vaccines, Zoster Vaccine Live (ZVL) versus a non-live adjuvanted subunit candidate vaccine (HZ/su), in the German population aged 50+ years split into 3 age cohorts, i.e. 50-59, 60-69 and 70+ years, respectively. A multi-cohort static Markov model was developed following age cohorts over their lifetime. Demographic data were obtained from the German federal statistical office. HZ incidence and the proportion of HZ individuals developing post-herpetic neuralgia (PHN) were derived from German specific sources. Age-specific vaccine efficacy and waning rates were based on published clinical trial data. Vaccine coverage for both vaccines was assumed to be 40%, with compliance of the second dose of the HZ/su vaccine of 70%. Sensitivity analyses were performed to assess the robustness of the results. It was estimated that, over the remaining lifetime since vaccination, the HZ/su vaccine would reduce the number of HZ cases by 725,233, 533,162 and 486,794 in the 3 age cohorts, respectively, compared with 198,477, 196,000 and 104,640, using ZVL. The number needed to vaccinate (NNV) to prevent one HZ case ranged from 8 to 11 using the HZ/su vaccine compared with 20 to 50 using ZVL. Corresponding NNV to prevent one PHN case ranged from 39 to 53 using the HZ/su vaccine compared with 94 to 198 using ZVL. Due to the higher, sustained vaccine efficacy, the candidate HZ/su vaccine demonstrated superior public health impact compared with ZVL.

Development and trial of vaccines against Brucella.

Science.gov (United States)

Lalsiamthara, Jonathan; Lee, John Hwa

2017-08-31

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 .

Application of a scalable plant transient gene expression platform for malaria vaccine development

Directory of Open Access Journals (Sweden)

Holger eSpiegel

2015-12-01

Full Text Available Despite decades of intensive research efforts there is currently no vaccine that provides sustained sterile immunity against malaria. In this context, a large number of targets from the different stages of the Plasmodium falciparum life cycle have been evaluated as vaccine candidates. None of these candidates has fulfilled expectations, and as long as we lack a single target that induces strain-transcending protective immune responses, combining key antigens from different life cycle stages seems to be the most promising route towards the development of efficacious malaria vaccines. After the identification of potential targets using approaches such as omics-based technology and reverse immunology, the rapid expression, purification and characterization of these proteins, as well as the generation and analysis of fusion constructs combining different promising antigens or antigen domains before committing to expensive and time consuming clinical development, represents one of the bottlenecks in the vaccine development pipeline. The production of recombinant proteins by transient gene expression in plants is a robust and versatile alternative to cell-based microbial and eukaryotic production platforms. The transfection of plant tissues and/or whole plants using Agrobacterium tumefaciens offers a low technical entry barrier, low costs and a high degree of flexibility embedded within a rapid and scalable workflow. Recombinant proteins can easily be targeted to different subcellular compartments according to their physicochemical requirements, including post-translational modifications, to ensure optimal yields of high quality product, and to support simple and economical downstream processing. Here we demonstrate the use of a plant transient expression platform based on transfection with A. tumefaciens as essential component of a malaria vaccine development workflow involving screens for expression, solubility and stability using fluorescent fusion

A qualitative analysis of the beliefs of Japanese anti-influenza vaccination website authors.

Science.gov (United States)

Okuhara, Tsuyoshi; Ishikawa, Hirono; Kato, Mio; Okada, Masafumi; Kiuchi, Takahiro

2018-04-01

Influenza vaccine coverage among the Japanese population is less than optimal. Anti-vaccination sentiment exists worldwide, and Japan is no exception. Anti-influenza vaccination activists argue on the internet that influenza vaccine has little or no efficacy and a high risk of side effects, and they warn that people should forgo vaccination. We conducted a qualitative analysis to explore beliefs underlying the messages of anti-influenza vaccination websites, by focusing on the perceived value these beliefs provide to those who hold them. We conducted online searches in January 2017 using two major Japanese search engines (Google Japan and Yahoo! Japan). Targeted websites were classified as "pro", "anti", or "neutral" depending on their claims. We applied a dual analytic approach-inductive thematic analysis and deductive interpretative analysis-to textual data of the anti websites. Of the 113 anti websites, we identified two themes that correspond to beliefs: it is necessary to 1) protect others against risks and exploitation related to influenza vaccination, and 2) educate others about hidden truths and self-determination. Authors of anti websites ascribed two values (people's "safety" and one's own "self-esteem") to their beliefs. Website authors may engage in anti-vaccination activities because they want to feel they are virtuous, saving people from harm caused by vaccination, and to boost their self-esteem, thinking "I am enlightening uninformed people." The anti-vaccination beliefs of website authors were considered to be strong. In promoting vaccination, it would be better not to target outright vaccine refusers, such as the authors of anti-vaccination websites; it is preferable to target vaccine-hesitant people who are more amenable to changing their attitudes toward vaccination. We discuss possible means of promoting vaccination in that target population.

The role of peptide and DNA vaccines in myeloid leukemia immunotherapy

Directory of Open Access Journals (Sweden)

Lin Chen

2013-02-01

Full Text Available Abstract While chemotherapy and targeted therapy are successful in inducing the remission of myeloid leukemia as acute myeloid leukemia (AML and chronic myeloid leukemia (CML, the disease remains largely incurable. This observation is likely due to the drug resistance of leukemic cells, which are responsible for disease relapse. Myeloid leukemia vaccines may most likely be beneficial for eradicating minimal residual disease after treatment with chemotherapy or targeted therapy. Several targeted immunotherapies using leukemia vaccines have been heavily investigated in clinical and preclinical trials. This review will focus on peptides and DNA vaccines in the context of myeloid leukemias, and optimal strategies for enhancing the efficacy of vaccines based on myeloid leukemia immunization are also summarized.

Vaccination against tuberculosis.

Science.gov (United States)

Martin, Carlos; Aguilo, Nacho; Gonzalo-Asensio, Jesús

2018-04-04

BCG (Bacille Calmette-Guérin) vaccination is included in the immunization schedule for tuberculosis endemic countries with a global coverage at birth close to 90% worldwide. BCG was attenuated from Mycobacterium bovis almost a century ago, and provides a strong protection against disseminated forms of the disease, though very limited against pulmonary forms of tuberculosis, responsible for transmission. Novel prophylactic tuberculosis vaccines are in clinical development either to replace BCG or to improve its protection against respiratory forms of the disease. There are limitations understanding the immunological responses involved and the precise type of long-lived immunity that new vaccines need to induce. MTBVAC is the first and only tuberculosis vaccine candidate based on live-attenuated Mycobacterium tuberculosis in clinical evaluation. MTBVAC clinical development plans to target tuberculosis prevention in newborns, as a BCG replacement strategy, and as secondary objective to be tested in adolescents and adults previous vaccinated with BCG. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

The Impact of Making Vaccines Thermostable in Niger’s Vaccine Supply Chain

Science.gov (United States)

Lee, Bruce Y.; Cakouros, Brigid E.; Assi, Tina-Marie; Connor, Diana L.; Welling, Joel; Kone, Souleymane; Djibo, Ali; Wateska, Angela R.; Pierre, Lionel; Brown, Shawn T.

2012-01-01

Objective Determine the effects on the vaccine cold chain of making different types of World Health Organization (WHO) Expanded Program on Immunizations (EPI) vaccines thermostable. Methods Utilizing a detailed computational, discrete-event simulation model of the Niger vaccine supply chain, we simulated the impact of making different combinations of the six current EPI vaccines thermostable. Findings Making any EPI vaccine thermostable relieved existing supply chain bottlenecks (especially at the lowest levels), increased vaccine availability of all EPI vaccines, and decreased cold storage and transport capacity utilization. By far, the most substantial impact came from making the pentavalent vaccine thermostable, increasing its own vaccine availability from 87% to 97% and the vaccine availabilities of all other remaining non-thermostable EPI vaccines to over 93%. By contrast, making each of the other vaccines thermostable had considerably less effect on the remaining vaccines, failing to increase the vaccine availabilities of other vaccines to more than 89%. Making tetanus toxoid vaccine along with the pentavalent thermostable further increased the vaccine availability of all EPI vaccines by at least 1–2%. Conclusion Our study shows the potential benefits of making any of Niger’s EPI vaccines thermostable and therefore supports further development of thermostable vaccines. Eliminating the need for refrigerators and freezers should not necessarily be the only benefit and goal of vaccine thermostability. Rather, making even a single vaccine (or some subset of the vaccines) thermostable could free up significant cold storage space for other vaccines, and thereby help alleviate supply chain bottlenecks that occur throughout the world. PMID:22789507

Use of Lot Quality Assurance Sampling (LQAS) to estimate vaccination coverage helps guide future vaccination efforts.

Science.gov (United States)

Alberti, K P; Guthmann, J P; Fermon, F; Nargaye, K D; Grais, R F

2008-03-01

Inadequate evaluation of vaccine coverage after mass vaccination campaigns, such as used in national measles control programmes, can lead to inappropriate public health responses. Overestimation of vaccination coverage may leave populations at risk, whilst underestimation can lead to unnecessary catch-up campaigns. The problem is more complex in large urban areas where vaccination coverage may be heterogeneous and the programme may have to be fine-tuned at the level of geographic subunits. Lack of accurate population figures in many contexts further complicates accurate vaccination coverage estimates. During the evaluation of a mass vaccination campaign carried out in N'Djamena, the capital of Chad, Lot Quality Assurance Sampling was used to estimate vaccination coverage. Using this method, vaccination coverage could be evaluated within smaller geographic areas of the city as well as for the entire city. Despite the lack of accurate population data by neighbourhood, the results of the survey showed heterogeneity of vaccination coverage within the city. These differences would not have been identified using a more traditional method. The results can be used to target areas of low vaccination coverage during follow-up vaccination activities.

Use of vaccines as a key antimicrobial stewardship strategy

African Journals Online (AJOL)

organism is resistant to specific antimicrobials or not. • Vaccines may inhibit carriage by decreasing acquisition and colonisation by bacteria, specifically those targeted by the vaccine. • Vaccines further reduce overall antibiotic consumption owing to indirect protection. This relates to the prevention of or reduction.

A general measles vaccination campaign in urban Guinea-Bissau

DEFF Research Database (Denmark)

Byberg, S.; Thysen, S. M.; Rodrigues, A.

2017-01-01

Background Measles vaccination campaigns targeting children aged 9–59 months are conducted every three years in Guinea-Bissau. Studies have demonstrated beneficial non-specific effects of measles vaccine. We compared mortality one year after the December 2012 measles vaccination campaign in Bissa...

Vaccines in Multiple Sclerosis.

Science.gov (United States)

Williamson, Eric M L; Chahin, Salim; Berger, Joseph R

2016-04-01

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.

Financing children's vaccines.

Science.gov (United States)

Nelson, E Anthony S; Sack, David; Wolfson, Lara; Walker, Damian G; Seng, Lim Fong; Steele, Duncan

2009-11-20

A 2006 Commonwealth Association of Paediatric Gastroenterology and Nutrition workshop on financing children's vaccines highlighted the potential for vaccines to control diarrhoea and other diseases as well as spur economic development through better health. Clear communication of vaccination value to decision-makers is required, together with sustainable funding mechanisms. GAVI and partners have made great progress providing funding for vaccines for children in the poorest countries but other solutions may be required to achieve the same gains in middle- and high-income countries. World Health Organization has a wealth of freely available country-level data on immunisation that academics and advocates can use to communicate the economic and health benefits of vaccines to decision-makers.

The therapeutic potential of plant-derived vaccines and antibodies.

Science.gov (United States)

Rodgers, P B; Hamilton, W D; Adair, J R

1999-03-01

The production of recombinant proteins in plants is reviewed with a particular focus on plant-derived vaccines and antibodies for human healthcare. Issues relating to foreign gene expression, such as protein yield, localisation and glycosylation are also considered. Emphasis is placed on reporting progress with preclinical and clinical evaluation of plant-derived vaccines and antibodies. An assessment is made of the likely future direction of research and development in this area.

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

Science.gov (United States)

Quach, Caroline

2014-12-01

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

Aspects of Microparticle Utilization for Potentiation of Novel Vaccines: Promises and Risks

Science.gov (United States)

Ilyinskii, P.

Many recombinant vaccines against novel (HIV, HCV) or ever-changing (influenza) infectious agents require the presence of adjuvants/delivery vehicles to induce strong immune responses. The necessity of their improvement led to the major effort towards development of vaccine delivery systems that are generally particulate (e.g., nano- and microparticles) and have comparable dimensions to the pathogens (viruses or bacteria). The mode of action of these adjuvants is not fully understood but implies the stimulation of the innate or antigen-specific immune responses, and/or the increase of antigen uptake or processing by antigen-presenting cells (APC). Moreover, enhancement of adjuvant activity through the use of micro- and nanoparticulate delivery systems often resulted from the synergistic effects producing immune responses stronger than those elicited by the adjuvant or delivery system alone. Among particulate adjuvants, biodegradable micro- and nanoparticles of poly(D,L-lactide-co-glycoside) (PLGA) or poly(D,L-lactide) (PLA) have been reported to enhance both humoral and cellular immune responses against an encapsulated protein antigen. Cationic and anionic polylactide co-glycolide (PLG) microparticles have been successfully used to adsorb a variety of agents, which include plasmid DNA, recombinant proteins and adjuvant active oligonucleotides and are also currently tested in several vaccine applications. Another approach envisions specific targeting of APC, especially peripheral DC and exploitation of particulate systems that are small enough for lymphatic uptake (polystyrene nanobeads). Micro- and nanoparticles offer the possibility of enhancement of their uptake by appropriate cells through manipulation of their surface properties. Still, questions regarding toxicity and molecular interaction between micro- and nano-particles and immune cells, tissues and whole organisms remain to be addressed. These risks and other possible side effects should be assessed in

Young multiethnic women's attitudes toward the HPV vaccine and HPV vaccination.

Science.gov (United States)

Wong, Li Ping

2008-11-01

To investigate the acceptability of the HPV vaccine among a multiethnic sample of young women in Malaysia. A qualitative study of 40 young women aged between 13 and 27 years recruited into 7 focus groups to discuss their knowledge of HPV infection, and their attitudes toward and acceptance of the HPV vaccine. The women were divided into Malay, Chinese, and Indian groups to allow for comparison among ethnicities. Poor knowledge about HPV did not influence the HPV vaccine's acceptability. Although participants were in favor of the vaccine, the majority preferred to delay vaccination because it is newly introduced, they did not perceive themselves to be at risk of HPV infection, or because of cost factors. Concerns were raised regarding the vaccine's safety, the potential to be perceived as promiscuous and sexually active, and whether the vaccine was halal. Promotion of the HPV vaccine should take account of social and cultural acceptability. The findings will help develop strategies for effective vaccination initiatives in a multiethnic and multireligious Asian society.

Characterization of fHbp, nhba (gna2132), nadA, porA, and sequence type in group B meningococcal case isolates collected in England and Wales during January 2008 and potential coverage of an investigational group B meningococcal vaccine.

Science.gov (United States)

Lucidarme, Jay; Comanducci, Maurizio; Findlow, Jamie; Gray, Stephen J; Kaczmarski, Edward B; Guiver, Malcolm; Vallely, Pamela J; Oster, Philipp; Pizza, Mariagrazia; Bambini, Stefania; Muzzi, Alessandro; Borrow, Ray

2010-06-01

Invasive disease caused by meningococcal capsular groups A, C, W-135, and Y is now preventable by means of glycoconjugate vaccines that target their respective polysaccharide capsules. The capsule of group B meningococci (MenB) is poorly immunogenic and may induce autoimmunity. Vaccines based on the major immunodominant surface porin, PorA, are effective against clonal epidemics but, thus far, have a limited scope of coverage against the wider MenB population at large. In an alternative approach, the first-generation, investigational, recombinant MenB (rMenB) plus outer membrane vesicle (OMV) (rMenB-OMV) vaccine contains a number of relatively conserved surface proteins, fHBP, NHBA (previously GNA2132), and NadA, alongside PorA P1.4-containing OMVs from the New Zealand MeNZB vaccine. MenB currently accounts for approximately 90% of cases of meningococcal disease in England and Wales. To assess potential rMenB-OMV vaccine coverage of pathogenic MenB isolates within this region, all English and Welsh MenB case isolates from January 2008 (n = 87) were genetically characterized with respect to fHBP, NHBA, NadA, and PorA. Alleles for fHbp, nhba, and porA were identified in all of the isolates, of which 22% were also found to harbor nadA alleles. On the basis of genotypic data and predicted immunological cross-reactivity, the potential level of rMenB-OMV vaccine coverage in England and Wales ranges from 66% to 100%.

Cost-effectiveness of a potential future Helicobacter pylori vaccine in the Netherlands: the impact of varying the discount rate for health.

Science.gov (United States)

de Vries, Robin; Klok, Rogier M; Brouwers, Jacobus R B J; Postma, Maarten J

2009-02-05

To estimate the cost-effectiveness of a potential Helicobacter pylori (HP) vaccine for the Dutch situation, we developed a Markov model. Several HP prevalence scenarios were assessed. Additionally, we assessed the impact of the discount rate for health on the outcomes, as this influence can be profound for vaccines. When applying the current discount rate of 1.5% for health, the expected cost-effectiveness of HP vaccination is estimated below the informal Dutch threshold of euro 20,000/LYG when the HP prevalence is assumed > or =20% in the Dutch population. In conclusion, we showed that HP vaccination could possibly be a cost-effective intervention. However, this depends to a large extend on the prevalence of HP in the population. Furthermore, we showed the large impact of the discount rate for health on the cost-effectiveness of a HP vaccination program, illustrative for other vaccination programs.

Negative Correlation between Circulating CD4+FOXP3+CD127− Regulatory T Cells and Subsequent Antibody Responses to Infant Measles Vaccine but Not Diphtheria–Tetanus–Pertussis Vaccine Implies a Regulatory Role

Directory of Open Access Journals (Sweden)

Jorjoh Ndure

2017-08-01

Full Text Available Regulatory T cells (Tregs play a key homeostatic role by suppressing immune responses. They have been targeted in mouse and human cancer studies to improve vaccine immunogenicity and tumor clearance. A number of commercially available drugs and experimental vaccine adjuvants have been shown to target Tregs. Infants have high numbers of Tregs and often have poor responses to vaccination, yet the role Tregs play in controlling vaccine immunogenicity has not been explored in this age group. Herein, we explore the role of CD4+FOXP3+CD127− Tregs in controlling immunity in infant males and females to vaccination with diphtheria–tetanus–whole cell pertussis (DTP and/or measles vaccine (MV. We find correlative evidence that circulating Tregs at the time of vaccination suppress antibody responses to MV but not DTP; and Tregs 4 weeks after DTP vaccination may suppress vaccine-specific cellular immunity. This opens the exciting possibility that Tregs may provide a future target for improved vaccine responses in early life, including reducing the number of doses of vaccine required. Such an approach would need to be safe and the benefits outweigh the risks, thus further research in this area is required.

Varicella zoster virus vaccines: potential complications and possible improvements.

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Silver, Benjamin; Zhu, Hua

2014-10-01

Varicella zoster virus (VZV) is the causative agent of varicella (chicken pox) and herpes zoster (shingles). After primary infection, the virus remains latent in sensory ganglia, and reactivates upon weakening of the cellular immune system due to various conditions, erupting from sensory neurons and infecting the corresponding skin tissue. The current varicella vaccine (v-Oka) is highly attenuated in the skin, yet retains its neurovirulence and may reactivate and damage sensory neurons. The reactivation is sometimes associated with postherpetic neuralgia (PHN), a severe pain along the affected sensory nerves that can linger for years, even after the herpetic rash resolves. In addition to the older population that develops a secondary infection resulting in herpes zoster, childhood breakthrough herpes zoster affects a small population of vaccinated children. There is a great need for a neuro-attenuated vaccine that would prevent not only the varicella manifestation, but, more importantly, any establishment of latency, and therefore herpes zoster. The development of a genetically-defined live-attenuated VZV vaccine that prevents neuronal and latent infection, in addition to primary varicella, is imperative for eventual eradication of VZV, and, if fully understood, has vast implications for many related herpesviruses and other viruses with similar pathogenic mechanisms.

HIV vaccine development: would more (public) money bring quicker results?

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Winsbury, R

1999-01-01

Globally, $200-250 million/year are devoted to HIV vaccine research. Most of those funds pay for basic research rather than product development. Moreover, most of the funds are aimed at the HIV strain commonly found in the US and Europe, and not at the strains common to Africa and other developing countries. While US President Bill Clinton set in 1997 a 10-year target for the development of an HIV vaccine, that target date is looking increasingly unlikely. International vaccine and pharmaceutical companies typically drive vaccine research and development. However, concern over the ultimate profitability of developing and marketing an HIV vaccine, and the fear of major litigation should an eventual vaccine go awry have caused such firms to shy away from investing large amounts of money into HIV vaccine development. These companies somehow have to be attracted back into the field. A World Bank special task force is slated to present its report by mid-1999 on possible funding mechanisms to promote HIV vaccine development. It remains to be resolved whether public funds could and should be used, perhaps through a pooled international vaccine development fund. 2 new International AIDS Vaccine Initiative projects are described.

Full-length genome sequence analysis of an avian leukosis virus subgroup J (ALV-J) as contaminant in live poultry vaccine: The commercial live vaccines might be a potential route for ALV-J transmission.

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Wang, P; Lin, L; Li, H; Shi, M; Gu, Z; Wei, P

2018-02-25

One avian leukosis virus subgroup J (ALV-J) strain was isolated from 67 commercial live poultry vaccines produced by various manufacturers during 2013-2016 in China. The complete genomes of the isolate were sequenced and it was found that the genes gag and pol of the strain were relatively conservative, while the gp85 gene of the strain GX14YYA1 had the highest similarities with a field strain GX14ZS14, which was isolated from the chickens of a farm that had once used the same vaccine as the one found to be contaminated with the GX14YYA1. This is the first report of ALV-J contaminant in live poultry vaccine in China. Our finding demonstrates that vaccination of the commercial live vaccines might be a potential new route for ALV-J transmission in chickens and highlights the need for more extensive monitoring of the commercial live vaccines in China. © 2018 Blackwell Verlag GmbH.

Plant-derived vaccine protects target animals against a viral disease

DEFF Research Database (Denmark)

Dalsgaard, Kristian; Uttenthal, Åse; Jones, T.D.

1997-01-01

The successful expression of animal or human virus epitopes on the surface of plant viruses has recently been demonstrated. These chimeric virus particles (CVPs) could represent a cost-effective and safe alternative to conventional animal cell-based vaccines. We report the insertion of oligonucle......The successful expression of animal or human virus epitopes on the surface of plant viruses has recently been demonstrated. These chimeric virus particles (CVPs) could represent a cost-effective and safe alternative to conventional animal cell-based vaccines. We report the insertion...

Vaccine-induced rabies case in a cow (Bos taurus): Molecular characterisation of vaccine strain in brain tissue.

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Vuta, Vlad; Picard-Meyer, Evelyne; Robardet, Emmanuelle; Barboi, Gheorghe; Motiu, Razvan; Barbuceanu, Florica; Vlagioiu, Constantin; Cliquet, Florence

2016-09-22

Rabies is a fatal neuropathogenic zoonosis caused by the rabies virus of the Lyssavirus genus, Rhabdoviridae family. The oral vaccination of foxes - the main reservoir of rabies in Europe - using a live attenuated rabies virus vaccine was successfully conducted in many Western European countries. In July 2015, a rabies vaccine strain was isolated from the brain tissues of a clinically suspect cow (Bos taurus) in Romania. The nucleotide analysis of both N and G gene sequences showed 100% identity between the rabid animal, the GenBank reference SAD B19 strain and five rabies vaccine batches used for the national oral vaccination campaign targeting foxes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dual miRNA targeting restricts host range and attenuates neurovirulence of flaviviruses.

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Konstantin A Tsetsarkin

2015-04-01

Full Text Available Mosquito-borne flaviviruses are among the most significant arboviral pathogens worldwide. Vaccinations and mosquito population control programs remain the most reliable means for flavivirus disease prevention, and live attenuated viruses remain one of the most attractive flavivirus vaccine platforms. Some live attenuated viruses are capable of infecting principle mosquito vectors, as demonstrated in the laboratory, which in combination with their intrinsic genetic instability could potentially lead to a vaccine virus reversion back to wild-type in nature, followed by introduction and dissemination of potentially dangerous viral strains into new geographic locations. To mitigate this risk we developed a microRNA-targeting approach that selectively restricts replication of flavivirus in the mosquito host. Introduction of sequences complementary to a mosquito-specific mir-184 and mir-275 miRNAs individually or in combination into the 3'NCR and/or ORF region resulted in selective restriction of dengue type 4 virus (DEN4 replication in mosquito cell lines and adult Aedes mosquitos. Moreover a combined targeting of DEN4 genome with mosquito-specific and vertebrate CNS-specific mir-124 miRNA can silence viral replication in two evolutionally distant biological systems: mosquitoes and mouse brains. Thus, this approach can reinforce the safety of newly developed or existing vaccines for use in humans and could provide an additional level of biosafety for laboratories using viruses with altered pathogenic or transmissibility characteristics.

Buccal and sublingual vaccine delivery.

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Kraan, Heleen; Vrieling, Hilde; Czerkinsky, Cecil; Jiskoot, Wim; Kersten, Gideon; Amorij, Jean-Pierre

2014-09-28

Because of their large surface area and immunological competence, mucosal tissues are attractive administration and target sites for vaccination. An important characteristic of mucosal vaccination is its ability to elicit local immune responses, which act against infection at the site of pathogen entry. However, mucosal surfaces are endowed with potent and sophisticated tolerance mechanisms to prevent the immune system from overreacting to the many environmental antigens. Hence, mucosal vaccination may suppress the immune system instead of induce a protective immune response. Therefore, mucosal adjuvants and/or special antigen delivery systems as well as appropriate dosage forms are required in order to develop potent mucosal vaccines. Whereas oral, nasal and pulmonary vaccine delivery strategies have been described extensively, the sublingual and buccal routes have received considerably less attention. In this review, the characteristics of and approaches for sublingual and buccal vaccine delivery are described and compared with other mucosal vaccine delivery sites. We discuss recent progress and highlight promising developments in the search for vaccine formulations, including adjuvants and suitable dosage forms, which are likely critical for designing a successful sublingual or buccal vaccine. Finally, we outline the challenges, hurdles to overcome and formulation issues relevant for sublingual or buccal vaccine delivery. Copyright © 2014. Published by Elsevier B.V.

Intentions to receive a potentially available Lyme disease vaccine in an urban sample.

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Fogel, Joshua; Kusz, Martin

2016-01-01

The only human Lyme disease vaccine of LYMErix was voluntarily removed from the market in the United States in 2002 for a number of reasons. A new human Lyme disease vaccine is currently being developed. We would like any future approved human Lyme disease vaccine to be of interest and marketable to consumers. We surveyed 714 participants to determine variables associated with intentions to receive a Lyme disease vaccine. Predictor variables included demographics, protection motivational theory, Lyme disease knowledge, Lyme disease preventive behaviors, beliefs and perceived health. We found in multivariate linear regression analyses that Asian/Asian American race/ethnicity (p Lyme disease vaccine. Although pharmaceutical companies may benefit by advertising a Lyme disease vaccine to Asian/Asian Americans and South Asians, marketers need to address and use approaches to interest those from other race/ethnicities. Also, marketers need to address the erroneous belief that vaccines are typically not safe in order to interest those with such beliefs to use a Lyme disease vaccine.

Analysis Of Vaccination Campaign Against Hpv And The Perspective Of Vaccinated Population

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Flávia Maria Palmeira Nunes

2017-04-01

Full Text Available Introduction:  The Ministry of Health has provided for the girls population aged nine to 13 years, the quadrivalent vaccine against Human Papillomavirus as a preventive measure for cancer of the cervix, with the initial proposal to achieve 80% of this population.  Objective:  To analyze the vaccine coverage and the perspective of the target population about the vaccine against the Human Papillomavirus.  Methods:  This was a quantitative and qualitative field research in descriptive character, conducted through the Information System of the National Program for Immunization and with a sample of 86 adolescents in the city of São José do Egito/PE/BR.  Results:  The vaccination coverage showed a reduction in sequence of the vaccination schedules of 19,53% in the first phase of the campaign and of 24.07% in the second phase. It was also noted that lack accurate information for more than 50% of respondents, 15.11% had local and / or systemic reactions and 89,53% of them expect positive results with the vaccine against the Human Papillomavirus.  Conclusion: The results showed a discontinuity in the prophylaxis scheme, but for the teenagers who took the vaccine there is confidence that the immunobiological has the desired effect, protecting them against viruses and future cancer of the cervix. Keywords: Health services; Vaccine; Adolescents; Human Papillomavirus.

Influenza vaccines: Evaluation of the safety profile

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Trombetta, Claudia Maria; Gianchecchi, Elena; Montomoli, Emanuele

2018-01-01

ABSTRACT The safety of vaccines is a critical factor in maintaining public trust in national vaccination programs. Vaccines are recommended for children, adults and elderly subjects and have to meet higher safety standards, since they are administered to healthy subjects, mainly healthy children. Although vaccines are strictly monitored before authorization, the possibility of adverse events and/or rare adverse events cannot be totally eliminated. Two main types of influenza vaccines are currently available: parenteral inactivated influenza vaccines and intranasal live attenuated vaccines. Both display a good safety profile in adults and children. However, they can cause adverse events and/or rare adverse events, some of which are more prevalent in children, while others with a higher prevalence in adults. The aim of this review is to provide an overview of influenza vaccine safety according to target groups, vaccine types and production methods. PMID:29297746

First Outbreak Response Using an Oral Cholera Vaccine in Africa: Vaccine Coverage, Acceptability and Surveillance of Adverse Events, Guinea, 2012

Science.gov (United States)

Luquero, Francisco J.; Grout, Lise; Ciglenecki, Iza; Sakoba, Keita; Traore, Bala; Heile, Melat; Dialo, Alpha Amadou; Itama, Christian; Serafini, Micaela; Legros, Dominique; Grais, Rebecca F.

2013-01-01

Background Despite World Health Organization (WHO) prequalification of two safe and effective oral cholera vaccines (OCV), concerns about the acceptability, potential diversion of resources, cost and feasibility of implementing timely campaigns has discouraged their use. In 2012, the Ministry of Health of Guinea, with the support of Médecins Sans Frontières organized the first mass vaccination campaign using a two-dose OCV (Shanchol) as an additional control measure to respond to the on-going nationwide epidemic. Overall, 316,250 vaccines were delivered. Here, we present the results of vaccination coverage, acceptability and surveillance of adverse events. Methodology/Principal Findings We performed a cross-sectional cluster survey and implemented adverse event surveillance. The study population included individuals older than 12 months, eligible for vaccination, and residing in the areas targeted for vaccination (Forécariah and Boffa, Guinea). Data sources were household interviews with verification by vaccination card and notifications of adverse events from surveillance at vaccination posts and health centres. In total 5,248 people were included in the survey, 3,993 in Boffa and 1,255 in Forécariah. Overall, 89.4% [95%CI:86.4–91.8%] and 87.7% [95%CI:84.2–90.6%] were vaccinated during the first round and 79.8% [95%CI:75.6–83.4%] and 82.9% [95%CI:76.6–87.7%] during the second round in Boffa and Forécariah respectively. The two dose vaccine coverage (including card and oral reporting) was 75.8% [95%CI: 71.2–75.9%] in Boffa and 75.9% [95%CI: 69.8–80.9%] in Forécariah respectively. Vaccination coverage was higher in children. The main reason for non-vaccination was absence. No severe adverse events were notified. Conclusions/Significance The well-accepted mass vaccination campaign reached high coverage in a remote area with a mobile population. Although OCV should not be foreseen as the long-term solution for global cholera control, they should be

Bioinformatics in New Generation Flavivirus Vaccines

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Penelope Koraka

2010-01-01

Full Text Available Flavivirus infections are the most prevalent arthropod-borne infections world wide, often causing severe disease especially among children, the elderly, and the immunocompromised. In the absence of effective antiviral treatment, prevention through vaccination would greatly reduce morbidity and mortality associated with flavivirus infections. Despite the success of the empirically developed vaccines against yellow fever virus, Japanese encephalitis virus and tick-borne encephalitis virus, there is an increasing need for a more rational design and development of safe and effective vaccines. Several bioinformatic tools are available to support such rational vaccine design. In doing so, several parameters have to be taken into account, such as safety for the target population, overall immunogenicity of the candidate vaccine, and efficacy and longevity of the immune responses triggered. Examples of how bio-informatics is applied to assist in the rational design and improvements of vaccines, particularly flavivirus vaccines, are presented and discussed.

Factors associated With Medicaid providers' recommendation of the HPV vaccine to low-income adolescent girls.

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Bynum, Shalanda A; Staras, Stephanie A S; Malo, Teri L; Giuliano, Anna R; Shenkman, Elizabeth; Vadaparampil, Susan T

2014-02-01

Human papillomavirus (HPV) vaccination in the United States remains a public health challenge with vaccine rates of 50%. Although health care providers can facilitate HPV vaccination, several factors may impede their ability to universally recommend the vaccine. To maximize the potential of HPV vaccines, it is important to understand challenges providers face in the clinical environment. The study sought to identify factors associated with recommendation of the HPV vaccine for low-income adolescents in the early (9-10), target (11-12), early adolescent catch-up (13-14), and late adolescent catch-up (15-17) vaccination groups. Surveys were mailed between October 2009 and April 2010 to a random sample of Florida-based physicians serving Medicaid-enrolled adolescents. Data were analyzed in 2013. Among early adolescents, discomfort discussing sexually transmitted infections (STIs) with teens (odds ratio [OR] = 1.75), difficulty ensuring vaccine completion (OR = .73), and discomfort discussing STIs with parents (OR = .44) were associated with recommendation. For target adolescents, discomfort discussing STIs with teens (OR = 2.45), time constraints (OR = .70), vaccine efficacy concerns (OR = .65), discomfort discussing STIs with parents (OR = .33), obstetrics/gynecology (OR = .25) and family medicine (OR = .24) specialty, and non-Hispanic black patient (OR = .15) were associated with recommendation. In early catch-up adolescents, concerns that teens will practice riskier behaviors (OR = .57), discomfort discussing STIs with parents (OR = .47), and family medicine specialty (OR = .20) were associated with recommendation. For late catch-up adolescents, family medicine specialty (OR = .13) was associated with recommendation. Modifiable factors that impede or influence provider recommendations of HPV vaccines can be addressed through intervention. Overall, findings suggest that efforts should focus on sexuality communication and family medicine specialty

Vaccines for the 21st century

Science.gov (United States)

Delany, Isabel; Rappuoli, Rino; De Gregorio, Ennio

2014-01-01

In the last century, vaccination has been the most effective medical intervention to reduce death and morbidity caused by infectious diseases. It is believed that vaccines save at least 2–3 million lives per year worldwide. Smallpox has been eradicated and polio has almost disappeared worldwide through global vaccine campaigns. Most of the viral and bacterial infections that traditionally affected children have been drastically reduced thanks to national immunization programs in developed countries. However, many diseases are not yet preventable by vaccination, and vaccines have not been fully exploited for target populations such as elderly and pregnant women. This review focuses on the state of the art of recent clinical trials of vaccines for major unmet medical needs such as HIV, malaria, TB, and cancer. In addition, we describe the innovative technologies currently used in vaccine research and development including adjuvants, vectors, nucleic acid vaccines, and structure-based antigen design. The hope is that thanks to these technologies, more diseases will be addressed in the 21st century by novel preventative and therapeutic vaccines. PMID:24803000

Economic value of dengue vaccine in Thailand.

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Lee, Bruce Y; Connor, Diana L; Kitchen, Sarah B; Bacon, Kristina M; Shah, Mirat; Brown, Shawn T; Bailey, Rachel R; Laosiritaworn, Yongjua; Burke, Donald S; Cummings, Derek A T

2011-05-01

With several candidate dengue vaccines under development, this is an important time to help stakeholders (e.g., policy makers, scientists, clinicians, and manufacturers) better understand the potential economic value (cost-effectiveness) of a dengue vaccine, especially while vaccine characteristics and strategies might be readily altered. We developed a decision analytic Markov simulation model to evaluate the potential health and economic value of administering a dengue vaccine to an individual (≤ 1 year of age) in Thailand from the societal perspective. Sensitivity analyses evaluated the effects of ranging various vaccine (e.g., cost, efficacy, side effect), epidemiological (dengue risk), and disease (treatment-seeking behavior) characteristics. A ≥ 50% efficacious vaccine was highly cost-effective [GDP) ($4,289)] up to a total vaccination cost of $60 and cost-effective [GDP ($12,868)] up to a total vaccination cost of $200. When the total vaccine series was $1.50, many scenarios were cost saving.

Applying Mathematical Tools to Accelerate Vaccine Development: Modeling Shigella Immune Dynamics

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Davis, Courtney L.; Wahid, Rezwanul; Toapanta, Franklin R.; Simon, Jakub K.

2013-01-01

We establish a mathematical framework for studying immune interactions with Shigella, a bacteria that kills over one million people worldwide every year. The long-term goal of this novel approach is to inform Shigella vaccine design by elucidating which immune components and bacterial targets are crucial for establishing Shigella immunity. Our delay differential equation model focuses on antibody and B cell responses directed against antigens like lipopolysaccharide in Shigella’s outer membrane. We find that antibody-based vaccines targeting only surface antigens cannot elicit sufficient immunity for protection. Additional boosting prior to infection would require a four-orders-of-magnitude increase in antibodies to sufficiently prevent epithelial invasion. However, boosting anti-LPS B memory can confer protection, which suggests these cells may correlate with immunity. We see that IgA antibodies are slightly more effective per molecule than IgG, but more total IgA is required due to spatial functionality. An extension of the model reveals that targeting both LPS and epithelial entry proteins is a promising avenue to advance vaccine development. This paper underscores the importance of multifaceted immune targeting in creating an effective Shigella vaccine. It introduces mathematical models to the Shigella vaccine development effort and lays a foundation for joint theoretical/experimental/clinical approaches to Shigella vaccine design. PMID:23589755

A clinically parameterized mathematical model of Shigella immunity to inform vaccine design.

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Courtney L Davis

Full Text Available We refine and clinically parameterize a mathematical model of the humoral immune response against Shigella, a diarrheal bacteria that infects 80-165 million people and kills an estimated 600,000 people worldwide each year. Using Latin hypercube sampling and Monte Carlo simulations for parameter estimation, we fit our model to human immune data from two Shigella EcSf2a-2 vaccine trials and a rechallenge study in which antibody and B-cell responses against Shigella's lipopolysaccharide (LPS and O-membrane proteins (OMP were recorded. The clinically grounded model is used to mathematically investigate which key immune mechanisms and bacterial targets confer immunity against Shigella and to predict which humoral immune components should be elicited to create a protective vaccine against Shigella. The model offers insight into why the EcSf2a-2 vaccine had low efficacy and demonstrates that at a group level a humoral immune response induced by EcSf2a-2 vaccine or wild-type challenge against Shigella's LPS or OMP does not appear sufficient for protection. That is, the model predicts an uncontrolled infection of gut epithelial cells that is present across all best-fit model parameterizations when fit to EcSf2a-2 vaccine or wild-type challenge data. Using sensitivity analysis, we explore which model parameter values must be altered to prevent the destructive epithelial invasion by Shigella bacteria and identify four key parameter groups as potential vaccine targets or immune correlates: 1 the rate that Shigella migrates into the lamina propria or epithelium, 2 the rate that memory B cells (BM differentiate into antibody-secreting cells (ASC, 3 the rate at which antibodies are produced by activated ASC, and 4 the Shigella-specific BM carrying capacity. This paper underscores the need for a multifaceted approach in ongoing efforts to design an effective Shigella vaccine.

A clinically parameterized mathematical model of Shigella immunity to inform vaccine design.

Science.gov (United States)

Davis, Courtney L; Wahid, Rezwanul; Toapanta, Franklin R; Simon, Jakub K; Sztein, Marcelo B

2018-01-01

We refine and clinically parameterize a mathematical model of the humoral immune response against Shigella, a diarrheal bacteria that infects 80-165 million people and kills an estimated 600,000 people worldwide each year. Using Latin hypercube sampling and Monte Carlo simulations for parameter estimation, we fit our model to human immune data from two Shigella EcSf2a-2 vaccine trials and a rechallenge study in which antibody and B-cell responses against Shigella's lipopolysaccharide (LPS) and O-membrane proteins (OMP) were recorded. The clinically grounded model is used to mathematically investigate which key immune mechanisms and bacterial targets confer immunity against Shigella and to predict which humoral immune components should be elicited to create a protective vaccine against Shigella. The model offers insight into why the EcSf2a-2 vaccine had low efficacy and demonstrates that at a group level a humoral immune response induced by EcSf2a-2 vaccine or wild-type challenge against Shigella's LPS or OMP does not appear sufficient for protection. That is, the model predicts an uncontrolled infection of gut epithelial cells that is present across all best-fit model parameterizations when fit to EcSf2a-2 vaccine or wild-type challenge data. Using sensitivity analysis, we explore which model parameter values must be altered to prevent the destructive epithelial invasion by Shigella bacteria and identify four key parameter groups as potential vaccine targets or immune correlates: 1) the rate that Shigella migrates into the lamina propria or epithelium, 2) the rate that memory B cells (BM) differentiate into antibody-secreting cells (ASC), 3) the rate at which antibodies are produced by activated ASC, and 4) the Shigella-specific BM carrying capacity. This paper underscores the need for a multifaceted approach in ongoing efforts to design an effective Shigella vaccine.

Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine

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E. Bridie Clemens

2018-03-01

Full Text Available Next-generation vaccines that utilize T cells could potentially overcome the limitations of current influenza vaccines that rely on antibodies to provide narrow subtype-specific protection and are prone to antigenic mismatch with circulating strains. Evidence from animal models shows that T cells can provide heterosubtypic protection and are crucial for immune control of influenza virus infections. This has provided hope for the design of a universal vaccine able to prime against diverse influenza virus strains and subtypes. However, multiple hurdles exist for the realisation of a universal T cell vaccine. Overall primary concerns are: extrapolating human clinical studies, seeding durable effective T cell resident memory (Trm, population human leucocyte antigen (HLA coverage, and the potential for T cell-mediated immune escape. Further comprehensive human clinical data is needed during natural infection to validate the protective role T cells play during infection in the absence of antibodies. Furthermore, fundamental questions still exist regarding the site, longevity and duration, quantity, and phenotype of T cells needed for optimal protection. Standardised experimental methods, and eventually simplified commercial assays, to assess peripheral influenza-specific T cell responses are needed for larger-scale clinical studies of T cells as a correlate of protection against influenza infection. The design and implementation of a T cell-inducing vaccine will require a consensus on the level of protection acceptable in the community, which may not provide sterilizing immunity but could protect the individual from severe disease, reduce the length of infection, and potentially reduce transmission in the community. Therefore, increasing the standard of care potentially offered by T cell vaccines should be considered in the context of pandemic preparedness and zoonotic infections, and in combination with improved antibody vaccine targeting methods

Alzheimer's disease: is a vaccine possible?

International Nuclear Information System (INIS)

Alves, R.P.S.; Yang, M.J.; Batista, M.T.; Ferreira, L.C.S.

2014-01-01

The cause of Alzheimer's disease is still unknown, but the disease is distinctively characterized by the accumulation of β-amyloid plaques and neurofibrillary tangles in the brain. These features have become the primary focus of much of the research looking for new treatments for the disease, including immunotherapy and vaccines targeting β-amyloid in the brain. Adverse effects observed in a clinical trial based on the β-amyloid protein were attributed to the presence of the target antigen and emphasized the relevance of finding safer antigen candidates for active immunization. For this kind of approach, different vaccine formulations using DNA, peptide, and heterologous prime-boost immunization regimens have been proposed. Promising results are expected from different vaccine candidates encompassing B-cell epitopes of the β-amyloid protein. In addition, recent results indicate that targeting another protein involved in the etiology of the disease has opened new perspectives for the effective prevention of the illness. Collectively, the evidence indicates that the idea of finding an effective vaccine for the control of Alzheimer's disease, although not without challenges, is a possibility

Alzheimer's disease: is a vaccine possible?

Energy Technology Data Exchange (ETDEWEB)

Alves, R.P.S. [Universidade de São Paulo, Instituto de Ciências Biomédicas II, Departamento de Microbiologia, Laboratório de Desenvolvimento de Vacinas, São Paulo, SP, Brasil, Laboratório de Desenvolvimento de Vacinas, Departamento de Microbiologia, Instituto de Ciências Biomédicas II, Universidade de São Paulo, São Paulo, SP (Brazil); Yang, M.J. [Instituto Butantan, Laboratório de Genética, São Paulo, SP, Brasil, Laboratório de Genética, Instituto Butantan, São Paulo, SP (Brazil); Batista, M.T.; Ferreira, L.C.S. [Universidade de São Paulo, Instituto de Ciências Biomédicas II, Departamento de Microbiologia, Laboratório de Desenvolvimento de Vacinas, São Paulo, SP, Brasil, Laboratório de Desenvolvimento de Vacinas, Departamento de Microbiologia, Instituto de Ciências Biomédicas II, Universidade de São Paulo, São Paulo, SP (Brazil)

2014-05-09

The cause of Alzheimer's disease is still unknown, but the disease is distinctively characterized by the accumulation of β-amyloid plaques and neurofibrillary tangles in the brain. These features have become the primary focus of much of the research looking for new treatments for the disease, including immunotherapy and vaccines targeting β-amyloid in the brain. Adverse effects observed in a clinical trial based on the β-amyloid protein were attributed to the presence of the target antigen and emphasized the relevance of finding safer antigen candidates for active immunization. For this kind of approach, different vaccine formulations using DNA, peptide, and heterologous prime-boost immunization regimens have been proposed. Promising results are expected from different vaccine candidates encompassing B-cell epitopes of the β-amyloid protein. In addition, recent results indicate that targeting another protein involved in the etiology of the disease has opened new perspectives for the effective prevention of the illness. Collectively, the evidence indicates that the idea of finding an effective vaccine for the control of Alzheimer's disease, although not without challenges, is a possibility.

The comprehensive ‘Communicate to Vaccinate’ taxonomy of communication interventions for childhood vaccination in routine and campaign contexts

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Jessica Kaufman

2017-05-01

Full Text Available Abstract Background Communication can be used to generate demand for vaccination or address vaccine hesitancy, and is crucial to successful childhood vaccination programmes. Research efforts have primarily focused on communication for routine vaccination. However, vaccination campaigns, particularly in low- or middle-income countries (LMICs, also use communication in diverse ways. Without a comprehensive framework integrating communication interventions from routine and campaign contexts, it is not possible to conceptualise the full range of possible vaccination communication interventions. Therefore, vaccine programme managers may be unaware of potential communication options and researchers may not focus on building evidence for interventions used in practice. In this paper, we broaden the scope of our existing taxonomy of communication interventions for routine vaccination to include communication used in campaigns, and integrate these into a comprehensive taxonomy of vaccination communication interventions. Methods Building on our taxonomy of communication for routine vaccination, we identified communication interventions used in vaccination campaigns through a targeted literature search; observation of vaccination activities in Cameroon, Mozambique and Nigeria; and stakeholder consultations. We added these interventions to descriptions of routine vaccination communication and categorised the interventions according to their intended purposes, building from an earlier taxonomy of communication related to routine vaccination. Results The comprehensive taxonomy groups communication used in campaigns and routine childhood vaccination into seven purpose categories: ‘Inform or Educate’; ‘Remind or Recall’; ‘Enhance Community Ownership’; ‘Teach Skills’; ‘Provide Support’; ‘Facilitate Decision Making’ and ‘Enable Communication’. Consultations with LMIC stakeholders and experts informed the taxonomy’s definitions and

A Review of OIE Country Status Recovery Using Vaccinate-to-Live Versus Vaccinate-to-Die Foot-and-Mouth Disease Response Policies I: Benefits of Higher Potency Vaccines and Associated NSP DIVA Test Systems in Post-Outbreak Surveillance.