Roč. 3, Suppl. 1 (2005), S7 ISSN 1214-021X. [Cells VI - Biological Days /18./. 24.10.2005-26.10.2005, České Budějovice] Institutional research plan: CEZ:AV0Z50520514 Keywords : tumour vaccines * HPV16 Subject RIV: EC - Immunology
Full Text Available Development of a preventive vaccine for HIV is the best hope of controlling the AIDS pandemic. HIV has, however, proved a difficult pathogen to vaccinate against because of its very high mutation rate and capability to escape immune responses. Neutralizing antibodies that can neutralize diverse field strains have so far proved difficult to induce. Adjuvanting these vaccines with cytokine plasmids and a "prime-boost," approach is being evaluated in an effort to induce both CTL and antibody responses and thereby have immune responses active against both infected cells and free viral particles, thereby necessitating fewer doses of recombinant protein to reach maximum antibodies titers. Although obstacles exist in evaluation of candidate HIV vaccines, evidence from natural history studies, new molecular tools in virology and immunology, new adjuvants, new gene expression systems, new antigen delivery systems, recent discoveries in HIV entry and pathogenesis, and promising studies of candidate vaccines in animal models have provided reasons to hope that developing a safe and effective AIDS vaccine is possible and within reach.
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Ross, Anna Laura; Bråve, Andreas; Scarlatti, Gabriella; Manrique, Amapola; Buonaguro, Luigi
The search for an HIV/AIDS vaccine is steadily moving ahead, generating and validating new concepts in terms of novel vectors for antigen delivery and presentation, new vaccine and adjuvant strategies, alternative approaches to design HIV-1 antigens for eliciting protective cross-neutralising antibodies, and identification of key mechanisms in HIV infection and modulation of the immune system. All these different perspectives are contributing to the unprecedented challenge of developing a protective HIV-1 vaccine. The high scientific value of this massive effort is its great impact on vaccinology as a whole, providing invaluable scientific information for the current and future development of new preventive vaccine as well as therapeutic knowledge-based infectious-disease and cancer vaccines. Copyright 2010 Elsevier Ltd. All rights reserved.
Yamamoto, Janet K; Sanou, Missa P; Abbott, Jeffrey R; Coleman, James K
Feline immunodeficiency virus (FIV) discovered in 1986 is a lentivirus that causes AIDS in domestic cats. FIV is classified into five subtypes (A-E), and all subtypes and circulating intersubtype recombinants have been identified throughout the world. A commercial FIV vaccine, consisting of inactivated subtype-A and -D viruses (Fel-O-Vax FIV, Fort Dodge Animal Health), was released in the United States in 2002. The United States Department of Agriculture approved the commercial release of Fel-O-Vax FIV based on two efficacy trials using 105 laboratory cats and a major safety trial performed on 689 pet cats. The prototype and commercial FIV vaccines had broad prophylactic efficacy against global FIV subtypes and circulating intersubtype recombinants. The mechanisms of cross-subtype efficacy are attributed to FIV-specific T-cell immunity. Findings from these studies are being used to define the prophylactic epitopes needed for an HIV-1 vaccine for humans.
Margaret I Johnston
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.
Kuipers, Kirsten; Van Selm, Saskia; van Opzeeland, Fred; Langereis, Jeroen D.; Verhagen, Lilly M.; Diavatopoulos, Dimitri A.; De Jonge, Marien I.
Vaccination has been one of the most successful strategies to reduce morbidity and mortality caused by respiratory infections. Recent evidence suggests that differences in the host genetic background and environmental factors may contribute to heterogeneity in the immune response to vaccination.
Patel, Rajan; Longini, Ira M; Halloran, M Elizabeth
In the event of pandemic influenza, only limited supplies of vaccine may be available. We use stochastic epidemic simulations, genetic algorithms (GA), and random mutation hill climbing (RMHC) to find optimal vaccine distributions to minimize the number of illnesses or deaths in the population, given limited quantities of vaccine. Due to the non-linearity, complexity and stochasticity of the epidemic process, it is not possible to solve for optimal vaccine distributions mathematically. However, we use GA and RMHC to find near optimal vaccine distributions. We model an influenza pandemic that has age-specific illness attack rates similar to the Asian pandemic in 1957-1958 caused by influenza A(H2N2), as well as a distribution similar to the Hong Kong pandemic in 1968-1969 caused by influenza A(H3N2). We find the optimal vaccine distributions given that the number of doses is limited over the range of 10-90% of the population. While GA and RMHC work well in finding optimal vaccine distributions, GA is significantly more efficient than RMHC. We show that the optimal vaccine distribution found by GA and RMHC is up to 84% more effective than random mass vaccination in the mid range of vaccine availability. GA is generalizable to the optimization of stochastic model parameters for other infectious diseases and population structures.
Aurisicchio, Luigi; Ciliberto, Gennaro
Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost
Chin'ombe, Nyasha; Ruhanya, Vurayai
More than decades have already elapsed since human immunodeficiency virus (HIV) was identified as the causative agent of acquired immunodeficiency syndrome (AIDS). The HIV has since spread to all parts of the world with devastating effects. In sub-saharan Africa, the HIV/AIDS epidemic has reached unprecedented proportions. Safe, effective and affordable HIV/AIDS vaccines for Africans are therefore urgently needed to contain this public health problem. Although, there are challenges, there are also scientific opportunities and strategies that can be exploited in the development of HIV/AIDS vaccines for Africa. The recent RV144 Phase III trial in Thailand has demonstrated that it is possible to develop a vaccine that can potentially elicit modest protective immunity against HIV infection. The main objective of this review is to outline the key scientific opportunities, challenges and strategies in HIV/AIDS vaccine development in Africa. PMID:26185576
Nogales, Aitor; Martínez-Sobrido, Luis
Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines. PMID:28025504
Roč. 18, č. 3 (2001), s. 475-478 ISSN 1019-6439 R&D Projects: GA MZd NC5526 Keywords : dendritic cell s * tumour vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.330, year: 2001
Roč. 47, č. 5 (2001), s. 153-155 ISSN 0015-5500 R&D Projects: GA MZd NC5526 Keywords : dendritic cell s * cancer vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.519, year: 2001
Matt David Thomas Hitchings
Full Text Available The 2014-6 West African Ebola epidemic highlights the need for rigorous, rapid clinical trial methods for vaccines. A challenge for trial design is making sample size calculations based on incidence within the trial, total vaccine effect, and intracluster correlation, when these parameters are uncertain in the presence of indirect effects of vaccination.We present a stochastic, compartmental model for a ring vaccination trial. After identification of an index case, a ring of contacts is recruited and either vaccinated immediately or after 21 days. The primary outcome of the trial is total vaccine effect, counting cases only from a pre-specified window in which the immediate arm is assumed to be fully protected and the delayed arm is not protected. Simulation results are used to calculate necessary sample size and estimated vaccine effect. Under baseline assumptions about vaccine properties, monthly incidence in unvaccinated rings and trial design, a standard sample-size calculation neglecting dynamic effects estimated that 7,100 participants would be needed to achieve 80% power to detect a difference in attack rate between arms, while incorporating dynamic considerations in the model increased the estimate to 8,900. This approach replaces assumptions about parameters at the ring level with assumptions about disease dynamics and vaccine characteristics at the individual level, so within this framework we were able to describe the sensitivity of the trial power and estimated effect to various parameters. We found that both of these quantities are sensitive to properties of the vaccine, to setting-specific parameters over which investigators have little control, and to parameters that are determined by the study design.Incorporating simulation into the trial design process can improve robustness of sample size calculations. For this specific trial design, vaccine effectiveness depends on properties of the ring vaccination design and on the
Ivancic, Jelena; Gulija, Tanja Kosutic; Forcic, Dubravko; Baricevic, Marijana; Jug, Renata; Mesko-Prejac, Majda; Mazuran, Renata
Eleven mumps vaccine strains, all containing live attenuated virus, have been used throughout the world. Although L-Zagreb mumps vaccine has been licensed since 1972, only its partial nucleotide sequence was previously determined (accession numbers , and ). Therefore, we sequenced the entire genome of L-Zagreb vaccine strain (Institute of Immunology Inc., Zagreb, Croatia). In order to investigate the genetic stability of the vaccine, sequences of both L-Zagreb master seed and currently produced vaccine batch were determined and no difference between them was observed. A phylogenetic analysis based on SH gene sequence has shown that L-Zagreb strain does not belong to any of established mumps genotypes and that it is most similar to old, laboratory preserved European strains (1950s-1970s). L-Zagreb nucleotide and deduced protein sequences were compared with other mumps virus sequences obtained from the GenBank. Emphasis was put on functionally important protein regions and known antigenic epitopes. The extensive comparisons of nucleotide and deduced protein sequences between L-Zagreb vaccine strain and other previously determined mumps virus sequences have shown that while the functional regions of HN, V, and L proteins are well conserved among various mumps strains, there can be a substantial amino acid difference in antigenic epitopes of all proteins and in functional regions of F protein. No molecular pattern was identified that can be used as a distinction marker between virulent and attenuated strains.
Rose, N F; Marx, P A; Luckay, A; Nixon, D F; Moretto, W J; Donahoe, S M; Montefiori, D; Roberts, A; Buonocore, L; Rose, J K
We developed an AIDS vaccine based on attenuated VSV vectors expressing env and gag genes and tested it in rhesus monkeys. Boosting was accomplished using vectors with glycoproteins from different VSV serotypes. Animals were challenged with a pathogenic AIDS virus (SHIV89.6P). Control monkeys showed a severe loss of CD4+ T cells and high viral loads, and 7/8 progressed to AIDS with an average time of 148 days. All seven vaccinees were initially infected with SHIV89.6P but have remained healthy for up to 14 months after challenge with low or undetectable viral loads. Protection from AIDS was highly significant (p = 0.001). VSV vectors are promising candidates for human AIDS vaccine trials because they propagate to high titers and can be delivered without injection.
Smita S. Iyer
Full Text Available Since the initial proof-of-concept studies examining the ability of antigen-encoded plasmid DNA to serve as an immunogen, DNA vaccines have evolved as a clinically safe and effective platform for priming HIV-specific cellular and humoral responses in heterologous “prime-boost” vaccination regimens. Direct injection of plasmid DNA into the muscle induces T- and B-cell responses against foreign antigens. However, the insufficient magnitude of this response has led to the development of approaches for enhancing the immunogenicity of DNA vaccines. The last two decades have seen significant progress in the DNA-based vaccine platform with optimized plasmid constructs, improved delivery methods, such as electroporation, the use of molecular adjuvants and novel strategies combining DNA with viral vectors and subunit proteins. These innovations are paving the way for the clinical application of DNA-based HIV vaccines. Here, we review preclinical studies on the DNA-prime/modified vaccinia Ankara (MVA-boost vaccine modality for HIV. There is a great deal of interest in enhancing the immunogenicity of DNA by engineering DNA vaccines to co-express immune modulatory adjuvants. Some of these adjuvants have demonstrated encouraging results in preclinical and clinical studies, and these data will be examined, as well.
Full Text Available Abstract Background The most often used mumps vaccine strains Jeryl Lynn (JL, RIT4385, Urabe-AM9, L-Zagreb and L-3 differ in immunogenicity and reactogenicity. Previous analyses showed that JL, Urabe-AM9 and L-3 are genetically heterogeneous. Results We identified the heterogeneity of L-Zagreb throughout the entire genome. Two major variants were defined: variant A being identical to the consensus sequence of viral seeds and vaccine(s and variant B which differs from variant A in three nucleotide positions. The difference between viral variants in L-Zagreb strain is insufficient for distinct viral strains to be defined. We demonstrated that proportion of variants in L-Zagreb viral population depends on cell substrate used for viral replication in vitro and in vivo. Conclusion L-Zagreb strain should be considered as a single strain composed of at least two variant viral genomes.
Kosutic-Gulija, Tanja; Forcic, Dubravko; Šantak, Maja; Ramljak, Ana; Mateljak-Lukacevic, Sanja; Mazuran, Renata
Background The most often used mumps vaccine strains Jeryl Lynn (JL), RIT4385, Urabe-AM9, L-Zagreb and L-3 differ in immunogenicity and reactogenicity. Previous analyses showed that JL, Urabe-AM9 and L-3 are genetically heterogeneous. Results We identified the heterogeneity of L-Zagreb throughout the entire genome. Two major variants were defined: variant A being identical to the consensus sequence of viral seeds and vaccine(s) and variant B which differs from variant A in three nucleotide positions. The difference between viral variants in L-Zagreb strain is insufficient for distinct viral strains to be defined. We demonstrated that proportion of variants in L-Zagreb viral population depends on cell substrate used for viral replication in vitro and in vivo. Conclusion L-Zagreb strain should be considered as a single strain composed of at least two variant viral genomes. PMID:18616793
Kosutic-Gulija, Tanja; Forcic, Dubravko; Santak, Maja; Ramljak, Ana; Mateljak-Lukacevic, Sanja; Mazuran, Renata
The most often used mumps vaccine strains Jeryl Lynn (JL), RIT4385, Urabe-AM9, L-Zagreb and L-3 differ in immunogenicity and reactogenicity. Previous analyses showed that JL, Urabe-AM9 and L-3 are genetically heterogeneous. We identified the heterogeneity of L-Zagreb throughout the entire genome. Two major variants were defined: variant A being identical to the consensus sequence of viral seeds and vaccine(s) and variant B which differs from variant A in three nucleotide positions. The difference between viral variants in L-Zagreb strain is insufficient for distinct viral strains to be defined. We demonstrated that proportion of variants in L-Zagreb viral population depends on cell substrate used for viral replication in vitro and in vivo. L-Zagreb strain should be considered as a single strain composed of at least two variant viral genomes.
Ce projet est une initiative conjointe de l'Université de Nairobi, au Kenya, et des universités du Manitoba et de Toronto, au Canada. L'objectif : faire de la Kenya AIDS Vaccine Initiative (KAVI) un centre d'excellence pour la formation aux essais de vaccins contre le VIH et à d'autres essais en matière de prévention à ...
VIH to AIDS transition has been modeled via a genetic algorithm that uses boom-boom principle and where population evolution is simulated with a cellular automaton based on SIR model. VIH to AIDS transition is signed by nucleation of infected cells and low probability of infection are obtained for different mutation rates in agreement with clinical results. A power law is obtained with a critical exponent close to the critical exponent of cubic, spherical percolation, colossal magnetic resonance, Ising Model and liquid-gas phase transition in heavy ion collisions. Computations were carried out at UAM-A Supercomputing Lab and author acknowledges financial support from Division of CBI at UAM-A.
Roman A Siddiqui
Full Text Available In HIV infection, TLR7-triggered IFN-α production exerts a direct antiviral effect through the inhibition of viral replication, but may also be involved in immune pathogenesis leading to AIDS. TLR7 could also be an important mediator of vaccine efficacy. In this study, we analyzed polymorphisms in the X-linked TLR7 gene in the rhesus macaque model of AIDS. Upon resequencing of the TLR7 gene in 36 rhesus macaques of Indian origin, 12 polymorphic sites were detected. Next, we identified three tightly linked single nucleotide polymorphisms (SNP as being associated with survival time. Genotyping of 119 untreated, simian immunodeficiency virus (SIV-infected male rhesus macaques, including an 'MHC adjusted' subset, revealed that the three TLR7 SNPs are also significantly associated with set-point viral load. Surprisingly, this effect was not observed in 72 immunized SIV-infected male monkeys. We hypothesize (i that SNP c.13G>A in the leader peptide is causative for the observed genotype-phenotype association and that (ii the underlying mechanism is related to RNA secondary structure formation. Therefore, we investigated a fourth SNP (c.-17C>T, located 17 bp upstream of the ATG translation initiation codon, that is also potentially capable of influencing RNA structure. In c.13A carriers, neither set-point viral load nor survival time were related to the c.-17C>T genotype. In c.13G carriers, by contrast, the c.-17C allele was significantly associated with prolonged survival. Again, no such association was detected among immunized SIV-infected macaques. Our results highlight the dual role of TLR7 in immunodeficiency virus infection and vaccination and imply that it may be important to control human AIDS vaccine trials, not only for MHC genotype, but also for TLR7 genotype.
Convergent ethical issues in HIV/AIDS, tuberculosis and malaria vaccine trials in Africa: Report from the WHO/UNAIDS African AIDS Vaccine Programme's Ethics, Law and Human Rights Collaborating Centre consultation, 10-11 February 2009, Durban, South Africa
Full Text Available Abstract Background Africa continues to bear a disproportionate share of the global HIV/AIDS, tuberculosis (TB and malaria burden. The development and distribution of safe, effective and affordable vaccines is critical to reduce these epidemics. However, conducting HIV/AIDS, TB, and/or malaria vaccine trials simultaneously in developing countries, or in populations affected by all three diseases, is likely to result in numerous ethical challenges. Methods In order to explore convergent ethical issues in HIV/AIDS, TB and malaria vaccine trials in Africa, the Ethics, Law and Human Rights Collaborating Centre of the WHO/UNAIDS African AIDS Vaccine Programme hosted a consultation on the Convergent Ethical Issues in HIV/AIDS, TB and Malaria Vaccine Trials in Africa in Durban, South Africa on the 10-11 February 2009. Results Key cross cutting ethical issues were prioritized during the consultation as community engagement; ancillary care obligations; care and treatment; informed consent; and resource sharing. Conclusion The consultation revealed that while there have been few attempts to find convergence on ethical issues between HIV/AIDS, TB and malaria vaccine trial fields to date, there is much common ground and scope for convergence work between stakeholders in the three fields.
Convergent ethical issues in HIV/AIDS, tuberculosis and malaria vaccine trials in Africa: Report from the WHO/UNAIDS African AIDS Vaccine Programme's Ethics, Law and Human Rights Collaborating Centre consultation, 10-11 February 2009, Durban, South Africa.
Mamotte, Nicole; Wassenaar, Douglas; Koen, Jennifer; Essack, Zaynab
Africa continues to bear a disproportionate share of the global HIV/AIDS, tuberculosis (TB) and malaria burden. The development and distribution of safe, effective and affordable vaccines is critical to reduce these epidemics. However, conducting HIV/AIDS, TB, and/or malaria vaccine trials simultaneously in developing countries, or in populations affected by all three diseases, is likely to result in numerous ethical challenges. In order to explore convergent ethical issues in HIV/AIDS, TB and malaria vaccine trials in Africa, the Ethics, Law and Human Rights Collaborating Centre of the WHO/UNAIDS African AIDS Vaccine Programme hosted a consultation on the Convergent Ethical Issues in HIV/AIDS, TB and Malaria Vaccine Trials in Africa in Durban, South Africa on the 10-11 February 2009. Key cross cutting ethical issues were prioritized during the consultation as community engagement; ancillary care obligations; care and treatment; informed consent; and resource sharing. The consultation revealed that while there have been few attempts to find convergence on ethical issues between HIV/AIDS, TB and malaria vaccine trial fields to date, there is much common ground and scope for convergence work between stakeholders in the three fields.
Gilmara Holanda da Cunha
Full Text Available Antiretroviral therapy has increased the survival of patients with HIV/AIDS, thus necessitating health promotion practice with immunization. Vaccines are critical components for protecting people living with HIV/AIDS (PLWHA. The purpose of study was to analyze the vaccination status of PLWHA in outpatient care in Fortaleza, Ceará, Brazil. Cross-sectional study performed from June 2014 to June 2015. The screening was done with patients in antiretroviral therapy, 420 patients underwent screening, but only 99 met the inclusion criteria. Data were collected for interviews using forms to characterize sociodemographic, clinical and vaccination situations. Only 14 patients had complete vaccination schedules. The most used vaccines were hepatitis B, influenza vaccine and 23-valent pneumococcal. There was no difference between men and women regarding the proportion of PLWHA with full vaccination schedule or between sex, skin color, marital status, sexual orientation, religion or occupational status. There was no difference between having or not having a complete vaccination schedule and age, years of education, family income or number of hospitalizations. CD4+ T-cells count of patients with incomplete immunization was lower than patients with complete immunization. Health education strategies can be done individually or in groups to explain the importance of vaccination and to remind about doses to be administered. Most patients did not have proper adherence to vaccination schedules, especially due to lack of guidance. Results implied that education in health is important for vaccination adhesion, knowledge of adverse events and continuation of schemes.
Parida, S.; Walsh, E.P.; Anderson, J.; Baron, M.D.; Barrett, T.
Rinderpest is an economically devastating disease of cattle (cattle plague), but a live-attenuated vaccine has been very successfully used in a global rinderpest eradication campaign. As a consequence, the endemic focus of the virus has been reduced to an area in eastern Africa known as the Kenya-Somali ecosystem. Although the vaccine is highly effective, it has a drawback in that vaccinated animals are serologically indistinguishable from those that have recovered from natural infection. In the final stages of the eradication campaign, when vaccination to control the spread of disease will only be used in emergencies to contain an outbreak, a marker vaccine would be a very useful tool to monitor possible wild virus spread outside the vaccination area. Marker vaccines for rinderpest, and other viruses with negative-sense RNA genomes, can now be produced using reverse genetics, and the development of such marker vaccines for rinderpest virus is described. (author)
Gloria S Omosa-Manyonyi
Full Text Available With the persistent challenges towards controlling the HIV epidemic, there is an ongoing need for research into HIV vaccines and drugs. Sub-Saharan African countries--worst affected by the HIV pandemic--have participated in the conduct of clinical trials for HIV vaccines. In Kenya, the Kenya AIDS Vaccine Initiative (KAVI at the University of Nairobi has conducted HIV vaccine clinical trials since 2001.Participants were recruited after an extensive informed consent process followed by screening to determine eligibility. Screening included an assessment of risk behavior, medical history and physical examination, and if clinically healthy, laboratory testing. In the absence of locally derived laboratory reference ranges, the ranges used in these trials were derived from populations in the West.Two hundred eighty-one participants were screened between 2003 and 2006 for two clinical trials. Of these, 167 (59.4% met the inclusion/exclusion criteria. Overall, laboratory abnormalities based on the non-indigenous laboratory references used were the most frequent reasons (61.4% for ineligibility. Medical abnormalities contributed 30.7% of the total reasons for ineligibility. Based on the laboratory reference intervals now developed from East and Southern Africa, those ineligible due to laboratory abnormalities would have been 46.3%. Of the eligible participants, 18.6% declined enrollment.Participant recruitment for HIV vaccine clinical trials is a rigorous and time-consuming exercise. Over 61% of the screening exclusions in clinically healthy people were due to laboratory abnormalities. It is essential that laboratory reference ranges generated from local populations for laboratory values be used in the conduct of clinical trials to avoid unnecessary exclusion of willing participants and to avoid over-reporting of adverse events for enrolled participants.Protocol IAVI VRC V001 . ClinicalTrials.gov NCT00124007 Protocol IAVI 010 (registration with
Geisbert, Thomas W.; Bailey, Michael; Geisbert, Joan B.; Asiedu, Clement; Roederer, Mario; Grazia-Pau, Maria; Custers, Jerome; Jahrling, Peter; Goudsmit, Jaap; Koup, Richard; Sullivan, Nancy J.
The immunogenicity and durability of genetic vaccines are influenced by the composition of gene inserts and choice of delivery vector. DNA vectors are a promising vaccine approach showing efficacy when combined in prime-boost regimens with recombinant protein or viral vectors, but they have shown
Claire Y-H Huang
Full Text Available We have developed a manufacturing strategy that can improve the safety and genetic stability of recombinant live-attenuated chimeric dengue vaccine (DENVax viruses. These viruses, containing the pre-membrane (prM and envelope (E genes of dengue serotypes 1-4 in the replicative background of the attenuated dengue-2 PDK-53 vaccine virus candidate, were manufactured under cGMP.After deriving vaccine viruses from RNA-transfected Vero cells, six plaque-purified viruses for each serotype were produced. The plaque-purified strains were then analyzed to select one stock for generation of the master seed. Full genetic and phenotypic characterizations of the master virus seeds were conducted to ensure these viruses retained the previously identified attenuating determinants and phenotypes of the vaccine viruses. We also assessed vector competence of the vaccine viruses in sympatric (Thai Aedes aegypti mosquito vectors.All four serotypes of master vaccine seeds retained the previously defined safety features, including all three major genetic loci of attenuation, small plaques, temperature sensitivity in mammalian cells, reduced replication in mosquito cell cultures, and reduced neurovirulence in new-born mice. In addition, the candidate vaccine viruses demonstrated greatly reduced infection and dissemination in Aedes aegypti mosquitoes, and are not likely to be transmissible by these mosquitoes. This manufacturing strategy has successfully been used to produce the candidate tetravalent vaccine, which is currently being tested in human clinical trials in the United States, Central and South America, and Asia.
Takai, Atsushi; Marusawa, Hiroyuki; Chiba, Tsutomu
Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis
Full Text Available Epstein-Barr virus is a very common human virus that infects 90% of human adults. EBV replicates in epithelial and B cells and causes infectious mononucleosis. EBV infection is also linked to various cancers, including Burkitt’s lymphoma and nasopharyngeal carcinomas, and autoimmune diseases such as multiple sclerosis. Currently, there are no effective drugs or vaccines to treat or prevent EBV infection. Herein, we applied a computer-aided strategy to design a prophylactic epitope vaccine ensemble from experimentally defined T and B cell epitopes. Such strategy relies on identifying conserved epitopes in conjunction with predictions of HLA presentation for T cell epitope selection and calculations of accessibility and flexibility for B cell epitope selection. The T cell component includes 14 CD8 T cell epitopes from early antigens and 4 CD4 T cell epitopes, targeted during the course of a natural infection and providing a population protection coverage of over 95% and 81.8%, respectively. The B cell component consists of 3 experimentally defined B cell epitopes from gp350 plus 4 predicted B cell epitopes from other EBV envelope glycoproteins, all mapping in flexible and solvent accessible regions. We discuss the rationale for the formulation and possible deployment of this epitope vaccine ensemble.
Amexis, G; Fineschi, N; Chumakov, K
The Urabe AM9 strain of mumps vaccine live is known for its genetic instability and some vaccines derived from this strain were withdrawn from the market due to an excessive number of vaccine-associated parotitis and meningitis cases. To identify the molecular basis of this instability, we determined complete nucleotide sequences of several stocks of the Urabe strain used for vaccine production by different manufacturers and of two clinical isolates from cases of vaccine-associated meningitis. In contrast to previously published studies relating the Lys335 --> Glu mutation in the viral HN gene with neurovirulence of mumps virus, we could not confirm any association of this mutation with the safety of mumps vaccine. Each of the three vaccine stocks studied had its own characteristic profile of mutations that was identified by cDNA sequencing and quantitated by mutant analysis by PCR and restriction enzyme cleavage. Determination of the mutational profile of mumps vaccine lots could allow vaccine manufacturers to characterize seed viruses and monitor the consistency of vaccine production to prevent emergence of virulent revertants.
Roč. 8, č. 3 (2008), s. 180-186 ISSN 1568-0096 Grant - others:EU-FP6-NoE Clinigene(XE) 018933 Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV 16 * genetically modified vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.316, year: 2008
Roč. 55, č. 6 (2009), s. 199-200 ISSN 0015-5500 Institutional research plan: CEZ:AV0Z50520514 Keywords : genetically modified vaccines * cancer surgery and chemotherapy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.924, year: 2009
Background Foot-and-mouth disease (FMD) is the most economically important and highly contagious disease of cloven-hoofed animals worldwide. Control of the disease has been mainly based on large-scale vaccinations with whole-virus inactivated vaccines. In recent years, a series of outbreaks of type O FMD occurred in China (including Chinese Taipei, Chinese Hong Kong) posed a tremendous threat to Chinese animal husbandry. Its causative agent, type O FMDV, has evolved into three topotypes (East–South Asia (ME-SA), Southeast Asia (SEA), Cathay (CHY)) in these regions, which represents an important obstacle to disease control. The available FMD vaccine in China shows generally good protection against ME-SA and SEA topotype viruses infection, but affords insufficient protection against some variants of the CHY topotype. Therefore, the choice of a new vaccine strain is of fundamental importance. Results The present study describes the generation of a full-length infectious cDNA clone of FMDV vaccine strain and a genetically modified virus with some amino acid substitutions in antigenic sites 1, 3, and 4, based on the established infectious clone. The recombinant viruses had similar growth properties to the wild O/HN/CHA/93 virus. All swine immunized with inactivated vaccine prepared from the O/HN/CHA/93 were fully protected from challenge with the viruses of ME-SA and SEA topotypes and partially protected against challenge with the virus of CHY topotype at 28 days post-immunization. In contrast, the swine inoculated with the genetically modified vaccine were completely protected from the infection of viruses of the three topotypes. Conclusions Some amino acid substitutions in the FMDV vaccine strain genome did not have an effect on the ability of viral replication in vitro. The vaccine prepared from genetically modified FMDV by reverse genetics significantly improved the protective efficacy to the variant of the CHY topotype, compared with the wild O/HN/CHA/93 virus
Full Text Available Abstract Background Foot-and-mouth disease (FMD is the most economically important and highly contagious disease of cloven-hoofed animals worldwide. Control of the disease has been mainly based on large-scale vaccinations with whole-virus inactivated vaccines. In recent years, a series of outbreaks of type O FMD occurred in China (including Chinese Taipei, Chinese Hong Kong posed a tremendous threat to Chinese animal husbandry. Its causative agent, type O FMDV, has evolved into three topotypes (East–South Asia (ME-SA, Southeast Asia (SEA, Cathay (CHY in these regions, which represents an important obstacle to disease control. The available FMD vaccine in China shows generally good protection against ME-SA and SEA topotype viruses infection, but affords insufficient protection against some variants of the CHY topotype. Therefore, the choice of a new vaccine strain is of fundamental importance. Results The present study describes the generation of a full-length infectious cDNA clone of FMDV vaccine strain and a genetically modified virus with some amino acid substitutions in antigenic sites 1, 3, and 4, based on the established infectious clone. The recombinant viruses had similar growth properties to the wild O/HN/CHA/93 virus. All swine immunized with inactivated vaccine prepared from the O/HN/CHA/93 were fully protected from challenge with the viruses of ME-SA and SEA topotypes and partially protected against challenge with the virus of CHY topotype at 28 days post-immunization. In contrast, the swine inoculated with the genetically modified vaccine were completely protected from the infection of viruses of the three topotypes. Conclusions Some amino acid substitutions in the FMDV vaccine strain genome did not have an effect on the ability of viral replication in vitro. The vaccine prepared from genetically modified FMDV by reverse genetics significantly improved the protective efficacy to the variant of the CHY topotype, compared with the
Ramezanpour, Bahar; Foucauld, de Jean; Kortekaas, Jeroen
On the 9th of November 2015, preceding the World Veterinary Vaccine Congress, a workshop was held to discuss how veterinary vaccines can be deployed more rapidly to appropriately respond to future epizootics in Europe. Considering their potential and unprecedented suitability for surge
Willocks, L J; Guerendiain, D; Austin, H I; Morrison, K E; Cameron, R L; Templeton, K E; DE Lima, V R F; Ewing, R; Donovan, W; Pollock, K G J
An outbreak of mumps within a student population in Scotland was investigated to assess the effect of previous vaccination on infection and clinical presentation, and any genotypic variation. Of the 341 cases, 79% were aged 18-24. Vaccination status was available for 278 cases of whom 84% had received at least one dose of mumps containing vaccine and 62% had received two. The complication rate was 5·3% (mainly orchitis), and 1·2% were admitted to hospital. Genetic sequencing of mumps virus isolated from cases across Scotland classified 97% of the samples as genotype G. Two distinct clusters of genotype G were identified, one circulating before the outbreak and the other thereafter, suggesting the virus that caused this outbreak was genetically different from the previously circulating virus. Whilst the poor vaccine effectiveness we found may be due to waning immunity over time, a contributing factor may be that the current mumps vaccine is less effective against some genotypes. Although the general benefits of the measles-mumps-rubella (MMR) vaccine should continue to be promoted, there may be value in reassessing the UK vaccination schedule and the current mumps component of the MMR vaccine.
Ramezanpour, B.; Kamphuis, Pim; Claassen, H.J.H.M.
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
Sheets, Rebecca L; Zhou, TieQun; Knezevic, Ivana
Clinical development of prophylactic HIV/AIDS vaccines presents many scientific challenges that result in challenges for regulators reviewing clinical trial applications (CTAs). The World Health Organization (WHO) has the responsibility to provide technical support to these regulators. The search for an HIV/AIDS vaccine will only succeed through well-designed, -conducted and -controlled human efficacy studies reviewed and approved by regulators in countries worldwide, particularly in countries where the epidemic has hit hardest, such as in sub-Saharan Africa and Asia. This review summarizes the current candidates in development and focuses on challenges regulators face when reviewing CTAs, such as the evolving landscape of "standard of prevention," trials in adolescents, adaptive trial designs, correlates of protection and their analysis, and access to successful vaccines. There are many unknowns in the field of HIV/AIDS vaccine development and often, there is not a clear right or wrong approach because of the scientific challenges described in this review. Consequently, regulators should not feel that decisions need be made in isolation, when there are many available international collaborative efforts and opportunities to seek expert advice. The WHO provides many such opportunities and support to regulators across the globe. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Christian M Parobek
Full Text Available Although Plasmodium vivax is a leading cause of malaria around the world, only a handful of vivax antigens are being studied for vaccine development. Here, we investigated genetic signatures of selection and geospatial genetic diversity of two leading vivax vaccine antigens--Plasmodium vivax merozoite surface protein 1 (pvmsp-1 and Plasmodium vivax circumsporozoite protein (pvcsp. Using scalable next-generation sequencing, we deep-sequenced amplicons of the 42 kDa region of pvmsp-1 (n = 44 and the complete gene of pvcsp (n = 47 from Cambodian isolates. These sequences were then compared with global parasite populations obtained from GenBank. Using a combination of statistical and phylogenetic methods to assess for selection and population structure, we found strong evidence of balancing selection in the 42 kDa region of pvmsp-1, which varied significantly over the length of the gene, consistent with immune-mediated selection. In pvcsp, the highly variable central repeat region also showed patterns consistent with immune selection, which were lacking outside the repeat. The patterns of selection seen in both genes differed from their P. falciparum orthologs. In addition, we found that, similar to merozoite antigens from P. falciparum malaria, genetic diversity of pvmsp-1 sequences showed no geographic clustering, while the non-merozoite antigen, pvcsp, showed strong geographic clustering. These findings suggest that while immune selection may act on both vivax vaccine candidate antigens, the geographic distribution of genetic variability differs greatly between these two genes. The selective forces driving this diversification could lead to antigen escape and vaccine failure. Better understanding the geographic distribution of genetic variability in vaccine candidate antigens will be key to designing and implementing efficacious vaccines.
Full Text Available The present study evaluates the immune response mediated by vaccination with cell complexes composed of irradiated B16 tumor cells and mouse fibroblasts genetically modified to produce GM-CSF. The animals were vaccinated with free B16 cells or cell complexes. We employed two gene plasmid constructions: one high producer (pMok and a low producer (p2F. Tumor transplant was performed by injection of B16 tumor cells. Plasma levels of total IgG and its subtypes were measured by ELISA. Tumor volumes were measured and survival curves were obtained. The study resulted in a cell complex vaccine able to stimulate the immune system to produce specific anti-tumor membrane proteins (TMP IgG. In the groups vaccinated with cells transfected with the low producer plasmid, IgG production was higher when we used free B16 cell rather than cell complexes. Nonspecific autoimmune response caused by cell complex was not greater than that induced by the tumor cells alone. Groups vaccinated with B16 transfected with low producer plasmid reached a tumor growth delay of 92% (p ≤ 0.01. When vaccinated with cell complex, the best group was that transfected with high producer plasmid, reaching a tumor growth inhibition of 56% (p ≤ 0.05. Significant survival (40% was only observed in the groups vaccinated with free transfected B16 cells.
Xu, Pei; Chen, Zhenhai; Phan, Shannon; Pickar, Adrian; He, Biao
Mumps is a highly contagious human disease, characterized by lateral or bilateral nonsuppurative swelling of the parotid glands and neurological complications that can result in aseptic meningitis or encephalitis. A mumps vaccination program implemented since the 1960s reduced mumps incidence by more than 99% and kept the mumps case numbers as low as hundreds of cases per year in the United States before 2006. However, a large mumps outbreak occurred in vaccinated populations in 2006 and again in 2009 in the United States, raising concerns about the efficacy of the vaccination program. Previously, we have shown that clinical isolate-based recombinant mumps viruses lacking expression of either the V protein (rMuVΔV) or the SH protein (rMuVΔSH) are attenuated in a neurovirulence test using newborn rat brains (P. Xu et al., Virology 417:126-136, 2011, http://dx.doi.org/10.1016/j.virol.2011.05.003; P. Xu et al., J. Virol. 86:1768-1776, 2012, http://dx.doi.org/10.1128/JVI.06019-11) and may be good candidates for vaccine development. In this study, we examined immunity induced by rMuVΔSH and rMuVΔV in mice. Furthermore, we generated recombinant mumps viruses lacking expression of both the V protein and the SH protein (rMuVΔSHΔV). Analysis of rMuVΔSHΔV indicated that it was stable in tissue culture cell lines. Importantly, rMuVΔSHΔV was immunogenic in mice, indicating that it is a promising candidate for mumps vaccine development.
Liu Ming; Wood, John M.; Ellis, Trevor; Krauss, Scott; Seiler, Patrick; Johnson, Christie; Hoffmann, Erich; Humberd, Jennifer; Hulse, Diane; Zhang Yun; Webster, Robert G.; Perez, Daniel R.
Options for the control of emerging and reemerging H5N1 influenza viruses include improvements in biosecurity and the use of inactivated vaccines. Commercially available H5N2 influenza vaccine prevents disease signs and reduces virus load but does not completely prevent virus shedding after challenge with H5N1 virus. By using reverse genetics, we prepared an H5N3 vaccine whose hemagglutinin is 99.6% homologous to that of A/CK/HK/86.3/02 (H5N1). We used the internal genes of A/PR/8/34 and the H5 of A/Goose/HK/437.4/99 (H5N1) after deletion of basic amino acids from its connecting peptide region. The resulting virus was not lethal to chicken embryos and grew to high HA titers in eggs, allowing preparation of HA protein-standardized vaccine in unconcentrated allantoic fluid. The N3 neuraminidase, derived from A/Duck/Germany/1215/73 (H2N3), permitted discrimination between vaccinated and naturally infected birds. The virus construct failed to replicate in quail and chickens. Similar to parental A/PR/8/34 (H1N1), it replicated in mice and ferrets and spread to the brains of mice; therefore, it should not be used as a live-attenuated vaccine. The H5N3 vaccine, at doses of 1.2 μg HA, induced HI antibodies in chickens and prevented death, signs of disease, and markedly reduced virus shedding after challenge with A/CK/HK/86.3/02 (H5N1) but did not provide sterilizing immunity. Thus, reverse genetics allows the inexpensive preparation of standardized, efficacious H5N3 poultry vaccines that may also reduce the reemergence of H5N1 genotypes
Bubeník, Jan; Mikyšková, Romana; Indrová, Marie; Vonka, V.; Šmahel, M.
Roč. 98, Suppl. 13 (2002), s. P 1001 ISSN 0020-7136. [UICC International Cancer Congress /18./. 30.06.2002-05.07.2002, Oslo] Institutional research plan: CEZ:AV0Z5052915 Keywords : HPV 16 * interleukins * vaccine therapy Subject RIV: EB - Genetics ; Molecular Biology
Full Text Available While wild type polio has been nearly eradicated there will be a need to continue immunisation programmes for some time because of the possibility of re-emergence and the existence of long term excreters of poliovirus. All vaccines in current use depend on growth of virus and most of the non-replicating (inactivated vaccines involve wild type viruses known to cause poliomyelitis. The attenuated vaccine strains involved in the eradication programme have been used to develop new inactivated vaccines as production is thought safer. However it is known that the Sabin vaccine strains are genetically unstable and can revert to a virulent transmissible form. A possible solution to the need for virus growth would be to generate empty viral capsids by recombinant technology, but hitherto such particles are so unstable as to be unusable. We report here the genetic manipulation of the virus to generate stable empty capsids for all three serotypes. The particles are shown to be extremely stable and to generate high levels of protective antibodies in animal models.
Baloch, M.J.; Soomro, B.A.
To develop improve crop varieties, the most basic elements are crossing of desirable parents to provide genetic variation for evaluation and selection of desirable plants among the progenies. In conventional plant breeding, gene transfer is achieved by back crossing or less frequently by recurrent selection. Both processes take several generations to reach to a point where genetic milieu of the parents remains. Plant breeders also face the most difficult situation when the desired gene is present in the entirely diverse species where wide crosses become inevitable. In addition, genomic disharmony, unfavourable genic interaction and chromosomal instability also account for limited success of wide hybridization in the field crops. Under such circumstances, tissue culture techniques, such as somaclonal variation, Embryo Rescue Technique and Somatic hybridization are the ultimate options. There may be other cases where desired genes are present in entirely different genera or organisms and crossings of donor with recipient is no more a concern. Plant breeders also spend much of their time manipulating quantitatively inherited traits such as yield, that have low heritability. These characters are assumed to be determined by a large number of genes each with minor and additive effects. Direct selection for such traits is less effective. Genetic Engineering approaches like isozymes and Restriction Fragment Length Polymorphism (RFLP) with heritability of 1.0 make the selection very efficient and accurate as indirect selection criteria for quantitatively inherited traits. Hence isozymes and RFLPs techniques can easily be exercised at cellular or seedling stages thus reducing the time and labour oriented screening of plants at maturity. Rather new approach such as polymerase chain reaction (PCR) will also be discussed in this article. (Orig./A.B.)
... page: //medlineplus.gov/ency/article/000594.htm HIV/AIDS To use the sharing features on this page, ... immunodeficiency virus (HIV) is the virus that causes AIDS. When a person becomes infected with HIV, the ...
Flannery, Brendan; Zimmerman, Richard K.; Gubareva, Larisa V.; Garten, Rebecca J.; Chung, Jessie R.; Nowalk, Mary Patricia; Jackson, Michael L.; Jackson, Lisa A.; Monto, Arnold S.; Ohmit, Suzanne E.; Belongia, Edward A.; McLean, Huong Q.; Gaglani, Manjusha; Piedra, Pedro A.; Mishin, Vasiliy P.; Chesnokov, Anton P.; Spencer, Sarah; Thaker, Swathi N.; Barnes, John R.; Foust, Angie; Sessions, Wendy; Xu, Xiyan; Katz, Jacqueline; Fry, Alicia M.
Background During the 2014–15 US influenza season, expanded genetic characterization of circulating influenza A(H3N2) viruses was used to assess the impact of genetic variability of influenza A(H3N2) viruses on influenza vaccine effectiveness (VE). Methods A novel pyrosequencing assay was used to determine genetic group based on hemagglutinin (HA) gene sequences of influenza A(H3N2) viruses from patients enrolled US Flu Vaccine Effectiveness network sites. Vaccine effectiveness was estimated using a test-negative design comparing vaccination among patients infected with influenza A(H3N2) viruses and uninfected patients. Results Among 9710 enrollees, 1868 (19%) tested positive for influenza A(H3N2); genetic characterization of 1397 viruses showed 1134 (81%) belonged to one HA genetic group (3C.2a) of antigenically drifted H3N2 viruses. Effectiveness of 2014–15 influenza vaccination varied by A(H3N2) genetic group from 1% (95% confidence interval [CI], −14% to 14%) against illness caused by antigenically drifted A(H3N2) group 3C.2a viruses versus 44% (95% CI, 16% to 63%) against illness caused by vaccine-like A(H3N2) group 3C.3b viruses. Conclusion Effectiveness of 2014–15 influenza vaccination varied by genetic group of influenza A(H3N2) virus. Changes in hemagglutinin genes related to antigenic drift were associated with reduced vaccine effectiveness. PMID:27190176
van Ballegooijen, W Marijn; van Houdt, Robin; Bruisten, Sylvia M; Boot, Hein J; Coutinho, Roel A; Wallinga, Jacco
The effect of vaccination programs on transmission of infectious disease is usually assessed by monitoring programs that rely on notifications of symptomatic illness. For monitoring of infectious diseases with a high proportion of asymptomatic cases or a low reporting rate, molecular sequence data combined with modern coalescent-based techniques offer a complementary tool to assess transmission. Here, the authors investigate the added value of using viral sequence data to monitor a vaccination program that was started in 1998 and was targeted against hepatitis B virus in men who have sex with men in Amsterdam, the Netherlands. The incidence in this target group, as estimated from the notifications of acute infections with hepatitis B virus, was low; therefore, there was insufficient power to show a significant change in incidence. In contrast, the genetic diversity, as estimated from the viral sequence collected from the target group, revealed a marked decrease after vaccination was introduced. Taken together, the findings suggest that introduction of vaccination coincided with a change in the target group toward behavior with a higher risk of infection. The authors argue that molecular sequence data provide a powerful additional monitoring instrument, next to conventional case registration, for assessing the impact of vaccination.
Full Text Available Abstract Background The lack of a uniform way for qualitative and quantitative evaluation of vaccine candidates under development led us to set up a standardized scheme for vaccine efficacy and safety evaluation. We developed and implemented molecular and immunology methods, and designed support tools for immunization data storage and analyses. Such collection can create a unique opportunity for immunologists to analyse data delivered from their laboratories. Results We designed and implemented GeVaDSs (Genetic Vaccine Decision Support system an interactive system for efficient storage, integration, retrieval and representation of data. Moreover, GeVaDSs allows for relevant association and interpretation of data, and thus for knowledge-based generation of testable hypotheses of vaccine responses. Conclusions GeVaDSs has been tested by several laboratories in Europe, and proved its usefulness in vaccine analysis. Case study of its application is presented in the additional files. The system is available at: http://gevads.cs.put.poznan.pl/preview/(login: viewer, password: password.
Sher L Hendrickson
Full Text Available The human mitochondrial genome includes only 13 coding genes while nuclear-encoded genes account for 99% of proteins responsible for mitochondrial morphology, redox regulation, and energetics. Mitochondrial pathogenesis occurs in HIV patients and genetically, mitochondrial DNA haplogroups with presumed functional differences have been associated with differential AIDS progression.Here we explore whether single nucleotide polymorphisms (SNPs within 904 of the estimated 1,500 genes that specify nuclear-encoded mitochondrial proteins (NEMPs influence AIDS progression among HIV-1 infected patients. We examined NEMPs for association with the rate of AIDS progression using genotypes generated by an Affymetrix 6.0 genotyping array of 1,455 European American patients from five US AIDS cohorts. Successfully genotyped SNPs gave 50% or better haplotype coverage for 679 of known NEMP genes. With a Bonferroni adjustment for the number of genes and tests examined, multiple SNPs within two NEMP genes showed significant association with AIDS progression: acyl-CoA synthetase medium-chain family member 4 (ACSM4 on chromosome 12 and peroxisomal D3,D2-enoyl-CoA isomerase (PECI on chromosome 6.Our previous studies on mitochondrial DNA showed that European haplogroups with presumed functional differences were associated with AIDS progression and HAART mediated adverse events. The modest influences of nuclear-encoded mitochondrial genes found in the current study add support to the idea that mitochondrial function plays a role in AIDS pathogenesis.
Mikyšková, Romana; Indrová, Marie; Šímová, Jana; Bieblová, Jana; Bubeník, Jan; Reiniš, Milan
Roč. 25, č. 6 (2011), s. 1683-1689 ISSN 1021-335X R&D Projects: GA ČR GA301/09/1024; GA ČR GA301/07/1410 Grant - others:EK(XE) EU-FP6-NOE018933 Institutional research plan: CEZ:AV0Z50520514 Keywords : gemcitabine * human papilloma virus * interleukin 12 * lung metastases * cellular vaccines * immunotherapy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.835, year: 2011
Billeter, M A; Naim, H Y; Udem, S A
An overview is given on the development of technologies to allow reverse genetics of RNA viruses, i.e., the rescue of viruses from cDNA, with emphasis on nonsegmented negative-strand RNA viruses (Mononegavirales), as exemplified for measles virus (MV). Primarily, these technologies allowed site-directed mutagenesis, enabling important insights into a variety of aspects of the biology of these viruses. Concomitantly, foreign coding sequences were inserted to (a) allow localization of virus replication in vivo through marker gene expression, (b) develop candidate multivalent vaccines against measles and other pathogens, and (c) create candidate oncolytic viruses. The vector use of these viruses was experimentally encouraged by the pronounced genetic stability of the recombinants unexpected for RNA viruses, and by the high load of insertable genetic material, in excess of 6 kb. The known assets, such as the small genome size of the vector in comparison to DNA viruses proposed as vectors, the extensive clinical experience of attenuated MV as vaccine with a proven record of high safety and efficacy, and the low production cost per vaccination dose are thus favorably complemented.
Wright, K E; Dimock, K; Brown, E G
The Urabe AM9 mumps vaccine is composed of a mixture of variants distinguishable by a difference at nucleotide (nt) 1081 of the hemagglutinin-neuraminidase (HN) gene (Brown, E.G., Dimock, K., Wright, K.E., 1996. The Urabe AM9 mumps vaccine is a mixture of viruses differing at amino acid (aa) 335 of the hemagglutinin-neuraminidase gene with one form associated with disease. J. Infect. Dis. 174, 619-622.). Further genetic and biological variation was detected in plaque purified viruses from the Urabe AM9 vaccine by examining the HN gene sequence, plaque morphology, cytopathic effects and growth in Vero cells, and temperature sensitivity (ts). Infection of Vero cells with plaque purified viruses with a G at nt 1081 of the HN gene produced large, clear plaques, caused significant CPE early after infection but yielded lower titres of virus than other purified viruses. None of these viruses were ts. In contrast, half of the plaque purified viruses with an A at nt 1081 were sensitive to a temperature of 39.5 degrees C. These viruses produced small plaques, caused significant CPE and grew to low titres. Two ts viruses possessed a unique aa substitution at aa 468 of HN. The remaining A(1081) viruses were not ts, produced large plaques but little CPE, and grew to titres 10-fold higher than the G(1081) viruses. Isolates of Urabe AM9 associated with post-vaccination illness were similar to these non-ts A(1081) viruses, but could be further sub-divided into two groups on the basis of a difference at aa 464 of HN. The post-vaccination isolates may represent insufficiently attenuated components of the vaccine, while the G(1081) and ts subset of A(1081) viruses may be more fully attenuated.
Fleury, Herve; Tumiotto, Camille; Bellecave, Pantxika; Recordon-Pinson, Patricia
The scientific and medical community is seeking to cure HIV. Several pathways have been or are being explored including therapeutic vaccination. Viroimmunological studies on primary infection as well as on elite controllers have demonstrated the importance of the cytotoxic CD8 response and have mainly oriented research on vaccine constructs toward this type of response. The results of these trials are clearly not commensurate with the hope placed in them. Might there be one or more uncontrolled variables? The genetics of patients need to be taken into consideration, especially their human lymphocyte antigen (HLA) alleles. There is a need to find a balance between the conservation of cytotoxic T lymphocyte (CTL) epitopes and presentation by HLA alleles. The pathway is a narrow one between adaptation of the virus to HLA I restriction and the definition of conserved proviral CTL epitopes presentable by HLA I alleles. It is likely that the genetics of patients will need to be considered for HIV-1 vaccine studies and that multidisciplinary collaboration will be essential in this field of infectious diseases.
Zhang, Yu; Sun, Jing; Wei, Yongwei; Li, Jianrong
Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey rhinotracheitis virus, is the causative agent of turkey rhinotracheitis and is associated with swollen head syndrome in chickens. aMPV belongs to the family Paramyxoviridae which includes many important human pathogens such as human respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and human parainfluenza virus type 3 (PIV3). The family also includes highly lethal emerging pathogens such as Nipah virus and Hendra virus, as well as agriculturally important viruses such as Newcastle disease virus (NDV). For many of these viruses, there is no effective vaccine. Here, we describe a reverse genetics approach to develop live attenuated aMPV vaccines by inhibiting the viral mRNA cap methyltransferase. The viral mRNA cap methyltransferase is an excellent target for the attenuation of paramyxoviruses because it plays essential roles in mRNA stability, efficient viral protein translation and innate immunity. We have described in detail the materials and methods used to generate recombinant aMPVs that lack viral mRNA cap methyltransferase activity. We have also provided methods to evaluate the genetic stability, pathogenesis, and immunogenicity of live aMPV vaccine candidates in turkeys.
Gray, Glenda E; Mayer, Kenneth H; Elizaga, Marnie L; Bekker, Linda-Gail; Allen, Mary; Morris, Lynn; Montefiori, David; De Rosa, Stephen C; Sato, Alicia; Gu, Niya; Tomaras, Georgia D; Tucker, Timothy; Barnett, Susan W; Mkhize, Nonhlanhla N; Shen, Xiaoying; Downing, Katrina; Williamson, Carolyn; Pensiero, Michael; Corey, Lawrence; Williamson, Anna-Lise
A phase I safety and immunogenicity study investigated South African AIDS Vaccine Initiative (SAAVI) HIV-1 subtype C (HIV-1C) DNA vaccine encoding Gag-RT-Tat-Nef and gp150, boosted with modified vaccinia Ankara (MVA) expressing matched antigens. Following the finding of partial protective efficacy in the RV144 HIV vaccine efficacy trial, a protein boost with HIV-1 subtype C V2-deleted gp140 with MF59 was added to the regimen. A total of 48 participants (12 U.S. participants and 36 Republic of South Africa [RSA] participants) were randomized to receive 3 intramuscular (i.m.) doses of SAAVI DNA-C2 of 4 mg (months 0, 1, and 2) and 2 i.m. doses of SAAVI MVA-C of 1.45 × 10(9) PFU (months 4 and 5) (n = 40) or of a placebo (n = 8). Approximately 2 years after vaccination, 27 participants were rerandomized to receive gp140/MF59 at 100 μg or placebo, as 2 i.m. injections, 3 months apart. The vaccine regimen was safe and well tolerated. After the DNA-MVA regimen, CD4(+) T-cell and CD8(+) T-cell responses occurred in 74% and 32% of the participants, respectively. The protein boost increased CD4(+) T-cell responses to 87% of the subjects. All participants developed tier 1 HIV-1C neutralizing antibody responses as well as durable Env binding antibodies that recognized linear V3 and C5 peptides. The HIV-1 subtype C DNA-MVA vaccine regimen showed promising cellular immunogenicity. Boosting with gp140/MF59 enhanced levels of binding and neutralizing antibodies as well as CD4(+) T-cell responses to HIV-1 envelope. (This study has been registered at ClinicalTrials.gov under registration no. NCT00574600 and NCT01423825.). Copyright © 2016 Gray et al.
Bellver Capella, Vincente
Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs.
Lucidarme, Jay; Gilchrist, Stefanie; Newbold, Lynne S; Gray, Stephen J; Kaczmarski, Edward B; Richardson, Lynne; Bennett, Julia S; Maiden, Martin C J; Findlow, Jamie; Borrow, Ray
The poor immunogenicity of the meningococcal serogroup B (MenB) capsule has led to the development of vaccines targeting subcapsular antigens, in particular the immunodominant and diverse outer membrane porin, PorA. These vaccines are largely strain specific; however, they offer limited protection against the diverse MenB-associated diseases observed in many industrialized nations. To broaden the scope of its protection, the multicomponent vaccine (4CMenB) incorporates a PorA-containing outer membrane vesicle (OMV) alongside relatively conserved recombinant protein components, including factor H-binding protein (fHbp), Neisseria adhesin A (NadA), and neisserial heparin-binding antigen (NHBA). The expression of PorA is unique to meningococci (Neisseria meningitidis); however, many subcapsular antigens are shared with nonpathogenic members of the genus Neisseria that also inhabit the nasopharynx. These organisms may elicit cross-protective immunity against meningococci and/or occupy a niche that might otherwise accommodate pathogens. The potential for 4CMenB responses to impact such species (and vice versa) was investigated by determining the genetic distribution of the primary 4CMenB antigens among diverse members of the common childhood commensal, Neisseria lactamica. All the isolates possessed nhba but were devoid of fhbp and nadA. The nhba alleles were mainly distinct from but closely related to those observed among a representative panel of invasive MenB isolates from the same broad geographic region. We made similar findings for the immunogenic typing antigen, FetA, which constitutes a major part of the 4CMenB OMV. Thus, 4CMenB vaccine responses may impact or be impacted by nasopharyngeal carriage of commensal neisseriae. This highlights an area for further research and surveillance should the vaccine be routinely implemented.
Taís Nóbrega de Sousa
Full Text Available The dependence of Plasmodium vivax on invasion mediated by Duffy binding protein (DBP makes this protein a prime candidate for development of a vaccine. However, the development of a DBP-based vaccine might be hampered by the high variability of the protein ligand (DBP(II, known to bias the immune response toward a specific DBP variant. Here, the hypothesis being investigated is that the analysis of the worldwide DBP(II sequences will allow us to determine the minimum number of haplotypes (MNH to be included in a DBP-based vaccine of broad coverage. For that, all DBP(II sequences available were compiled and MNH was based on the most frequent nonsynonymous single nucleotide polymorphisms, the majority mapped on B and T cell epitopes. A preliminary analysis of DBP(II genetic diversity from eight malaria-endemic countries estimated that a number between two to six DBP haplotypes (17 in total would target at least 50% of parasite population circulating in each endemic region. Aiming to avoid region-specific haplotypes, we next analyzed the MNH that broadly cover worldwide parasite population. The results demonstrated that seven haplotypes would be required to cover around 60% of DBP(II sequences available. Trying to validate these selected haplotypes per country, we found that five out of the eight countries will be covered by the MNH (67% of parasite populations, range 48-84%. In addition, to identify related subgroups of DBP(II sequences we used a Bayesian clustering algorithm. The algorithm grouped all DBP(II sequences in six populations that were independent of geographic origin, with ancestral populations present in different proportions in each country. In conclusion, in this first attempt to undertake a global analysis about DBP(II variability, the results suggest that the development of DBP-based vaccine should consider multi-haplotype strategies; otherwise a putative P. vivax vaccine may not target some parasite populations.
Nóbrega de Sousa, Taís; Carvalho, Luzia Helena; Alves de Brito, Cristiana Ferreira
The dependence of Plasmodium vivax on invasion mediated by Duffy binding protein (DBP) makes this protein a prime candidate for development of a vaccine. However, the development of a DBP-based vaccine might be hampered by the high variability of the protein ligand (DBP(II)), known to bias the immune response toward a specific DBP variant. Here, the hypothesis being investigated is that the analysis of the worldwide DBP(II) sequences will allow us to determine the minimum number of haplotypes (MNH) to be included in a DBP-based vaccine of broad coverage. For that, all DBP(II) sequences available were compiled and MNH was based on the most frequent nonsynonymous single nucleotide polymorphisms, the majority mapped on B and T cell epitopes. A preliminary analysis of DBP(II) genetic diversity from eight malaria-endemic countries estimated that a number between two to six DBP haplotypes (17 in total) would target at least 50% of parasite population circulating in each endemic region. Aiming to avoid region-specific haplotypes, we next analyzed the MNH that broadly cover worldwide parasite population. The results demonstrated that seven haplotypes would be required to cover around 60% of DBP(II) sequences available. Trying to validate these selected haplotypes per country, we found that five out of the eight countries will be covered by the MNH (67% of parasite populations, range 48-84%). In addition, to identify related subgroups of DBP(II) sequences we used a Bayesian clustering algorithm. The algorithm grouped all DBP(II) sequences in six populations that were independent of geographic origin, with ancestral populations present in different proportions in each country. In conclusion, in this first attempt to undertake a global analysis about DBP(II) variability, the results suggest that the development of DBP-based vaccine should consider multi-haplotype strategies; otherwise a putative P. vivax vaccine may not target some parasite populations.
Full Text Available Radha Mahendran,1 Suganya Jeyabaskar,1 Gayathri Sitharaman,1 Rajamani Dinakaran Michael,2 Agnal Vincent Paul1 1Department of Bioinformatics, 2Centre for Fish Immunology, School of Life Sciences, Vels University, Pallavaram, Chennai, Tamil Nadu, India Abstract: Edwardsiella tarda and Flavobacterium columnare are two important intracellular pathogenic bacteria that cause the infectious diseases edwardsiellosis and columnaris in wild and cultured fish. Prediction of major histocompatibility complex (MHC binding is an important issue in T-cell epitope prediction. In a healthy immune system, the T-cells must recognize epitopes and induce the immune response. In this study, T-cell epitopes were predicted by using in silico immunoinformatics approach with the help of bioinformatics tools that are less expensive and are not time consuming. Such identification of binding interaction between peptides and MHC alleles aids in the discovery of new peptide vaccines. We have reported the potential peptides chosen from the outer membrane proteins (OMPs of E. tarda and F. columnare, which interact well with MHC class I alleles. OMPs from E. tarda and F. columnare were selected and analyzed based on their antigenic and immunogenic properties. The OMPs of the genes TolC and FCOL_04620, respectively, from E. tarda and F. columnare were taken for study. Finally, two epitopes from the OMP of E. tarda exhibited excellent protein–peptide interaction when docked with MHC class I alleles. Five epitopes from the OMP of F. columnare had good protein–peptide interaction when docked with MHC class I alleles. Further in vitro studies can aid in the development of potential peptide vaccines using the predicted peptides. Keywords: E. tarda, F. columnare, edwardsiellosis, columnaris, T-cell epitopes, MHC class I, peptide vaccine, outer membrane proteins
Full Text Available Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, sub-unit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in L. donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen1-/- in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated
Albright, Kendra S.; Gavigan, Karen
HIV/AIDS infections are growing at an alarming rate for young adults. In 2009, youth, ages 13-29, accounted for 39% of all new HIV infections in the U.S. (Division of HIV/ AIDS Prevention, Centers for Disease Control (CDC), 2011). South Carolina ranks eighth in the nation for new HIV cases, while the capital city of Columbia ranks seventh…
In a research milestone reported in the June 20 issue of the journal Science, scientists have developed a minimally modified version of HIV-1, the virus that causes AIDS in infected humans, that is capable of causing progressive infection and AIDS i
By Frank Blanchard, Staff Writer, and Jeff Lifson, Guest Writer In a research milestone reported in the June 20 issue of the journal Science, scientists have developed a minimally modified version of HIV-1, the virus that causes AIDS in infected humans, that is capable of causing progressive infection and AIDS in monkeys. The advance should help create more authentic animal
Lloyd-Jones, Katie; Mahapatra, Mana; Upadhyaya, Sasmita; Paton, David J; Babu, Aravindh; Hutchings, Geoff; Parida, Satya
Foot-and-mouth disease (FMD) is endemic in Eastern Africa with circulation of multiple serotypes of the virus in the region. Most of the outbreaks are caused by serotype O followed by serotype A. The lack of concerted FMD control programmes in Africa has provided little incentive for vaccine producers to select vaccines that are tailored to circulating regional isolates creating further negative feedback to deter the introduction of vaccine-based control schemes. In this study a total of 80 serotype O FMD viruses (FMDV) isolated from 1993 to 2012 from East and North Africa were characterized by virus neutralisation tests using bovine antisera to three existing (O/KEN/77/78, O/Manisa and O/PanAsia-2) and three putative (O/EA/2002, O/EA/2009 and O/EA/2010) vaccine strains and by capsid sequencing. Genetically, these viruses were grouped as either of East African origin with subdivision into four topotypes (EA-1, 2, 3 and 4) or of Middle-East South Asian (ME-SA) topotype. The ME-SA topotype viruses were mainly detected in Egypt and Libya reflecting the trade links with the Middle East countries. There was good serological cross-reactivity between the vaccine strains and most of the field isolates analysed, indicating that vaccine selection should not be a major constraint for control of serotype O FMD by vaccination, and that both local and internationally available commercial vaccines could be used. The O/KEN/77/78 vaccine, commonly used in the region, exhibited comparatively lower percent in vitro match against the predominant topotypes (EA-2 and EA-3) circulating in the region whereas O/PanAsia-2 and O/Manisa vaccines revealed broader protection against East African serotype O viruses, even though they genetically belong to the ME-SA topotype. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Lechuga, Julia; Swain, Geoffrey; Weinhardt, Lance S.
The human papillomavirus (HPV) is a precursor of cervical cancer. In 2006, the Federal Drug Administration licensed a vaccine to protect against four types of HPV. Three years postlicensure of the vaccine, HPV vaccination is still fraught with controversy. To date, research suggests that contrary to popular notions, parents are less concerned with controversies on moral issues and more with uncertainty regarding because long-term safety of a drug is resolved after licensure. This study was designed to understand whether mothers from diverse ethnicities perceive a need for a decision support tool. Results suggest that the design of a culturally tailored decision support tool may help guide parents through the decision-making process. PMID:21444922
Lechuga, Julia; Swain, Geoffrey; Weinhardt, Lance S
The human papillomavirus (HPV) is a precursor of cervical cancer. In 2006, the Federal Drug Administration licensed a vaccine to protect against four types of HPV. Three years postlicensure of the vaccine, HPV vaccination is still fraught with controversy. To date, research suggests that contrary to popular notions, parents are less concerned with controversies on moral issues and more with uncertainty regarding because long-term safety of a drug is resolved after licensure. This study was designed to understand whether mothers from diverse ethnicities perceive a need for a decision support tool. Results suggest that the design of a culturally tailored decision support tool may help guide parents through the decision-making process.
Gelaye, E.; Belay, A.; Melesse, A.G.; Jenberie, S.; Yami, M.; Loitsch, A.; Tuppurainen, E.; Grabherr, R.; Diallo, A.; Lamien, C.E.
Sheeppox virus (SPPV), goatpox virus (GTPV) and lumpy skin disease virus (LSDV) of the genus Capripoxvirus (CaPV) cause capripox disease in sheep, goats and cattle, respectively. These viruses are not strictly host-specific and their geographical distribution is complex. In Ethiopia, where sheep, goats and cattle are all affected, a live attenuated vaccine strain (KS1-O180) is used for immunization of both small ruminants and cattle. Although occurrences of the disease in vaccinated cattle are frequently reported, information on the circulating isolates and their relation to the vaccine strain in use are still missing. The present study addressed the parameters associated with vaccination failure in Ethiopia
Clarke, Jihong Liu; Waheed, Mohammad Tahir; Lössl, Andreas G; Martinussen, Inger; Daniell, Henry
Aquaculture, the fastest growing food-producing sector, now accounts for nearly 50 % of the world's food fish (FAO in The state of world fisheries and aquaculture. FAO, Rome, 2010). The global aquaculture production of food fish reached 62.7 million tonnes in 2011 and is continuously increasing with an estimated production of food fish of 66.5 million tonnes in 2012 (a 9.4 % increase in 1 year, FAO, www.fao.org/fishery/topic/16140 ). Aquaculture is not only important for sustainable protein-based food fish production but also for the aquaculture industry and economy worldwide. Disease prevention is the key issue to maintain a sustainable development of aquaculture. Widespread use of antibiotics in aquaculture has led to the development of antibiotic-resistant bacteria and the accumulation of antibiotics in the environment, resulting in water and soil pollution. Thus, vaccination is the most effective and environmentally-friendly approach to combat diseases in aquaculture to manage fish health. Furthermore, when compared to >760 vaccines against human diseases, there are only about 30 fish vaccines commercially available, suggesting the urgent need for development and cost-effective production of fish vaccines for managing fish health, especially in the fast growing fish farming in Asia where profit is minimal and therefore given high priority. Plant genetic engineering has made significant contributions to production of biotech crops for food, feed, valuable recombinant proteins etc. in the past three decades. The use of plants for vaccine production offers several advantages such as low cost, safety and easy scaling up. To date a large number of plant-derived vaccines, antibodies and therapeutic proteins have been produced for human health, of which a few have been made commercially available. However, the development of animal vaccines in plants, especially fish vaccines by genetic engineering, has not yet been addressed. Therefore, there is a need to exploit
Sanders, Barbara P; Edo-Matas, Diana; Papic, Natasa; Schuitemaker, Hanneke; Custers, Jerome H H V
Safety of vaccines can be compromised by contamination with adventitious agents. One potential source of adventitious agents is a vaccine seed, typically derived from historic clinical isolates with poorly defined origins. Here we generated synthetic poliovirus seeds derived from chemically synthesized DNA plasmids encoding the sequence of wild-type poliovirus strains used in marketed inactivated poliovirus vaccines. The synthetic strains were phenotypically identical to wild-type polioviruses as shown by equivalent infectious titers in culture supernatant and antigenic content, even when infection cultures are scaled up to 10-25L bioreactors. Moreover, the synthetic seeds were genetically stable upon extended passaging on the PER.C6 cell culture platform. Use of synthetic seeds produced on the serum-free PER.C6 cell platform ensures a perfectly documented seed history and maximum control over starting materials. It provides an opportunity to maximize vaccine safety which increases the prospect of a vaccine end product that is free from adventitious agents. Copyright © 2015 Elsevier Ltd. All rights reserved.
Gannavaram, Sreenivas; Dey, Ranadhir; Avishek, Kumar; Selvapandiyan, Angamuthu; Salotra, Poonam; Nakhasi, Hira L
Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood-borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, subunit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in Leishmania donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters, and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines, e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen(-/-) in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal
Gannavaram, Sreenivas; Dey, Ranadhir; Avishek, Kumar; Selvapandiyan, Angamuthu; Salotra, Poonam; Nakhasi, Hira L.
Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood-borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, subunit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in Leishmania donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters, and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines, e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen−/− in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal
Haddad-Boubaker, S; Ould-Mohamed-Abdallah, M V; Ben-Yahia, A; Triki, H
Recombination is one of the major mechanisms of evolution in poliovirus. In this work, recombination was assessed in children during vaccination with OPV and among circulating vaccine strains isolated in Tunisia during the last 15 years in order to identify a possible role of recombination in the response to the vaccine or the acquisition of an increased transmissibility. This study included 250 poliovirus isolates: 137 vaccine isolates, excreted by children during primary vaccination with OPV and 113 isolates obtained from acute flaccid paralytic (AFP) cases and healthy contacts. Recombination was first assessed using a double PCR-RFLP, and sequencing. Nineteen per cent of recombinant strains were identified: 20% of strains excreted by vaccinees among 18% of circulating strains. The proportion of recombinant in isolates of serotype1 was very low in the two groups while the proportions of recombinants in serotypes 2 and 3 were different. In vaccinees, the frequency of recombinants in serotype3 decreased during the course of vaccination: 54% after the first dose, 32% after the second and 14% after the third dose. These results suggest that recombination enhances the ability of serotype3 vaccine strains to induce an immune response. Apart from recent vaccination, it may contribute to a more effective transmissibility of vaccine strains among human population. Copyright © 2009 Elsevier Masson SAS. All rights reserved.
Sheets, Rebecca L; Rangavajhula, Vijaya; Pullen, Jeffrey K; Butler, Chris; Mehra, Vijay; Shapiro, Stuart; Pensiero, Michael
The Division of AIDS Vaccine Research Program funds the discovery and development of HIV/AIDS vaccine candidates. Basic researchers, having discovered a potential vaccine in the laboratory, next want to take that candidate into the clinic to test the concept in humans, to see if it translates. Many of them have heard of "cGMP" and know that they are supposed to make a "GMP product" to take into the clinic, but often they are not very familiar with what "cGMP" means and why these good practices are so important. As members of the Vaccine Translational Research Branch, we frequently get asked "can't we use the material we made in the lab in the clinic?" or "aren't Phase 1 studies exempt from cGMP?" Over the years, we have had many experiences where researchers or their selected contract manufacturing organizations have not applied an appropriate degree of compliance with cGMP suitable for the clinical phase of development. We share some of these experiences and the lessons learned, along with explaining the importance of cGMP, just what cGMP means, and what they can assure, in an effort to de-mystify this subject and facilitate the rapid and safe translational development of HIV vaccines. Published by Elsevier Ltd.
Sheets, Rebecca L.; Rangavajhula, Vijaya; Pullen, Jeffrey K.; Butler, Chris; Mehra, Vijay; Shapiro, Stuart
The Division of AIDS Vaccine Research Program funds the discovery and development of HIV/AIDS vaccine candidates. Basic researchers, having discovered a potential vaccine in the laboratory, next want to take that candidate into the clinic to test the concept in humans, to see if it translates. Many of them have heard of “cGMP” and know that they are supposed to make a “GMP product” to take into the clinic, but often they are not very familiar with what “cGMP” means and why these good practices are so important. As members of the Vaccine Translational Research Branch, we frequently get asked “can’t we use the material we made in the lab in the clinic?” or “aren’t Phase 1 studies exempt from cGMP?” Over the years, we have had many experiences where researchers or their selected contract manufacturing organizations have not applied an appropriate degree of compliance with cGMP suitable for the clinical phase of development. We share some of these experiences and the lessons learned, along with explaining the importance of cGMP, just what cGMP means, and what they can assure, in an effort to de-mystify this subject and facilitate the rapid and safe translational development of HIV vaccines. PMID:25698494
Sibeli B S Cembranelli
Full Text Available Entamoeba gingivalis is considered an oral commensal but demonstrates a pathogenic potential associated with periodontal disease in immunocompromised individuals. Therefore, this study evaluated the occurrence, opportunistic conditions, and intraspecific genetic variability of E. gingivalis in HIV(+/AIDS patients. Entamoeba gingivalis was studied using fresh examination (FE, culture, and PCR from bacterial plaque samples collected from 82 HIV(+/AIDS patients. Genetic characterization of the lower ribosomal subunit of region 18S (18S-SSU rRNA was conducted in 9 positive samples using low-stringency single specific primer PCR (LSSP-PCR and sequencing analysis. Entamoeba gingivalis was detected in 63.4% (52/82 of the samples. No association was detected between the presence of E. gingivalis and the CD4(+ lymphocyte count (≤200 cells/mm(3 (p = 0.912 or viral load (p = 0.429. The LSSP-PCR results helped group E. gingivalis populations into 2 polymorphic groups (68.3% similarity: group I, associated with 63.6% (7/11 of the samples, and group II, associated with 36.4% (4/11 of the samples, which shared 74% and 83.7% similarity and association with C and E isolates from HIV(- individuals, respectively. Sequencing of 4 samples demonstrated 99% identity with the reference strain ATCC 30927 and also showed 2 divergent clusters, similar to those detected by LSSP-PCR. Opportunistic behavior of E. gingivalis was not detected, which may be related to the use of highly active antiretroviral therapy by all HIV(+/AIDS patients. The high occurrence of E. gingivalis in these patients can be influenced by multifactorial components not directly related to the CD4(+ lymphocyte counts, such as cholesterol and the oral microbiota host, which could mask the potential opportunistic ability of E. gingivalis. The identification of the 18S SSU-rRNA polymorphism by LSSP-PCR and sequencing analysis provides the first evidence of genetic variability in E. gingivalis
Moghram, Basem Ameen; Nabil, Emad; Badr, Amr
T-cell epitope structure identification is a significant challenging immunoinformatic problem within epitope-based vaccine design. Epitopes or antigenic peptides are a set of amino acids that bind with the Major Histocompatibility Complex (MHC) molecules. The aim of this process is presented by Antigen Presenting Cells to be inspected by T-cells. MHC-molecule-binding epitopes are responsible for triggering the immune response to antigens. The epitope's three-dimensional (3D) molecular structure (i.e., tertiary structure) reflects its proper function. Therefore, the identification of MHC class-II epitopes structure is a significant step towards epitope-based vaccine design and understanding of the immune system. In this paper, we propose a new technique using a Genetic Algorithm for Predicting the Epitope Structure (GAPES), to predict the structure of MHC class-II epitopes based on their sequence. The proposed Elitist-based genetic algorithm for predicting the epitope's tertiary structure is based on Ab-Initio Empirical Conformational Energy Program for Peptides (ECEPP) Force Field Model. The developed secondary structure prediction technique relies on Ramachandran Plot. We used two alignment algorithms: the ROSS alignment and TM-Score alignment. We applied four different alignment approaches to calculate the similarity scores of the dataset under test. We utilized the support vector machine (SVM) classifier as an evaluation of the prediction performance. The prediction accuracy and the Area Under Receiver Operating Characteristic (ROC) Curve (AUC) were calculated as measures of performance. The calculations are performed on twelve similarity-reduced datasets of the Immune Epitope Data Base (IEDB) and a large dataset of peptide-binding affinities to HLA-DRB1*0101. The results showed that GAPES was reliable and very accurate. We achieved an average prediction accuracy of 93.50% and an average AUC of 0.974 in the IEDB dataset. Also, we achieved an accuracy of 95
Gao, Li; Qi, Xiaole; Li, Kai; Gao, Honglei; Gao, Yulong; Qin, Liting; Wang, Yongqiang; Wang, Xiaomei
Due to the problems associated with traditional methods for infectious bursal disease virus (IBDV) vaccine development and the pressure of evolution and variation of very virulent strains, it is urgent to develop IBDV vaccine rapidly with novel approaches. Using reverse genetics, the aim of this study was to generate a tailored vaccine strain (rGtHLJVP2) with its VP2 gene similar to very virulent IBDV (vvIBDV) to prevent the prevalence of IBDV. Characteristics of rGtHLJVP2 were evaluated in both cell culture and SPF chickens. rGtHLJVP2 replicated well as its parental strain Gt in vitro and in vivo. Immunization of SPF chickens with rGtHLJVP2 resulted in comparable antibody titers against IBDV as that of the medium virulent live vaccine B87, which was significant higher than that of attenuated vaccine Gt. Challenge studies with 10(4)ELD(50) of prevalent homogeneous or heterogeneous vvIBDV revealed complete (100%) protection in the groups immunized with rGtHLJVP2. No significant clinical and pathological lesions were observed in chickens immunized with rGtHLJVP2. Our data demonstrated that rGtHLJVP2 could be used as a novel vaccine candidate for prevention against vvIBDV. Copyright © 2011. Published by Elsevier Ltd.
Liman, Martin; Peiser, Lieselotte; Zimmer, Gert; Pröpsting, Marcus; Naim, Hassan Y; Rautenschlein, Silke
In this study we demonstrated the use of an oculonasally delivered poly(D,L-lactic-co-glycolic acid) microparticle (PLGA-MP)-based and genetically engineered vaccination strategy in the avian system. An avian Metapneumovirus (aMPV) fusion (F) protein-encoding plasmid vaccine and the corresponding recombinant protein vaccine were produced and bound to or encapsulated by PLGA-MP, respectively. The PLGA-MP as the controlled release system was shown in vitro to not induce any cytopathic effects and to efficiently deliver the F protein-based aMPV-vaccines to avian cells for further processing. Vaccination of turkeys was carried out by priming with an MP-bound F protein-encoding plasmid vaccine and a booster-vaccination with an MP-encapsulated recombinant F protein. Besides the prime-boost F-specific vaccinated birds, negative control birds inoculated with a mock-MP prime-boost regimen as well as non-vaccinated birds and live vaccinated positive control birds were included in the study. The MP-based immunization of turkeys via the oculonasal route induced systemic humoral immune reactions as well as local and systemic cellular immune reactions, and had no adverse effects on the upper respiratory tract. The F protein-specific prime-boost strategy induced partial protection. After challenge the F protein-specific MP-vaccinated birds showed less clinical signs and histopathological lesions than control birds of mock MP-vaccinated and non-vaccinated groups did. The vaccination improved viral clearance and induced accumulation of local and systemic CD4+ T cells when compared to the mock MP-vaccination. It also induced systemic aMPV-neutralizing antibodies. The comparison of mock- and F protein-specific MP-vaccinated birds to non-vaccinated control birds suggests that aMPV-specific effects as well as adjuvant effects mediated by MP may have contributed to the overall protective effect.
Qin, Xiaosheng; Huang, Guohe; Liu, Lei
A genetic-algorithm-aided stochastic optimization (GASO) model was developed in this study for supporting regional air quality management under uncertainty. The model incorporated genetic algorithm (GA) and Monte Carlo simulation techniques into a general stochastic chance-constrained programming (CCP) framework and allowed uncertainties in simulation and optimization model parameters to be considered explicitly in the design of least-cost strategies. GA was used to seek the optimal solution of the management model by progressively evaluating the performances of individual solutions. Monte Carlo simulation was used to check the feasibility of each solution. A management problem in terms of regional air pollution control was studied to demonstrate the applicability of the proposed method. Results of the case study indicated the proposed model could effectively communicate uncertainties into the optimization process and generate solutions that contained a spectrum of potential air pollutant treatment options with risk and cost information. Decision alternatives could be obtained by analyzing tradeoffs between the overall pollutant treatment cost and the system-failure risk due to inherent uncertainties.
Goot, van der J.A.; Boven, van M.; Stegeman, A.; Water, van de S.G.P.; Jong, de M.C.M.; Koch, G.
Domestic ducks play an important role in the epidemiology of H5N1 avian influenza. Although it is known that vaccines that have a high homology with the challenge virus are able to prevent infection in ducks, little is yet known about the ability of genetically more distant vaccines in preventing
Afifi Manal A
Egypt. Egyptian H5N1-AIVs are constantly undergoing genetic changes and reveal a complex pattern of drifts. These findings raise the concerns about the value of using influenza vaccines in correlation with the development of antigenic drift in influenza epidemics.
Neafsey, Daniel E; Juraska, Michal; Bedford, Trevor
Background The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the c......Background The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes...... protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. Results In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.......3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine...
Yan, Dongrei; Li, Xiaolei; Zhang, Yong; Yang, Jianfang; Zhu, Shuangli; Wang, Dongyan; Zhang, Chuangye; Zhu, Hui; Xu, Wenbo
The World Health Organization redefined the type 2 vaccine-derived poliovirus (VDPV) in 2010. To study the genetic characteristics and evolution of type 2 VDPV under this new definition, we conducted genome sequencing and analyses of type 2 VDPVs isolated from one patient with acute flaccid paralysis in Shanxi province (China) in 2014. Nucleotide sequencing revealed that the full-length of type 2 VDPV is 7439 bases encoding 2207 amino acids with no insertion or deletion of nucleotides compared with Sabin2. One nucleotide substitution identified as a key determinant of the attenuated phenotype of the Sabin 2 strain (A-G reversion at nucleotide nt 481 in the 5-end of the untranslated region) had reverted in the Shanxi type 2 VDPV. The other known key determinant of the attenuated phenotype of the Sabin 2 strain (U-->C reversion at nt2909 in the VP1 coding region that caused a Ile143Thr substitution in VP1) had not reverted in the Shanxi VDPV. The Shanxi type 2 VDPV was S2/S1 recombinant, the crossover site of which mapped to the 3-end of the 3D region (between nt 6247 and nt 6281). A phylogentic tree based on the VP1 coding region showed that evolution of the Shanxi type 2 VDPV was independent of other type 2 VDPVs detected worldwide. We estimated that the strain circulated for approximately = 11 months in the population according to the known evolution rate. The present study confirmed that the Chinese Polio Laboratory Network could discover the VDPV promptly and that it played an important part in maintenance of a polio-free China.
Koyama, Yoshiyuki; Ito, Tomoko; Hasegawa, Aya; Eriguchi, Masazumi; Inaba, Toshio; Ushigusa, Takahiro; Sugiura, Kikuya
To examine the potential of exosomes derived from the tumor cells, which had been genetically modified to express a Mycobacterium tuberculosis antigen, as a cancer vaccine aimed at overcoming the weak immunogenicity of tumor antigens. We transfected B16 melanoma cells with a plasmid encoding the M. tuberculosis antigen, early secretory antigenic target-6 (ESAT-6). The secreted exosomes bearing both tumor-associated antigens and the pathogenic antigen (or their epitopes) were collected. When the exosomes were injected into foot pads of mice, they significantly (p exosomes significantly suppressed (p exosomes derived from the non-transfected B16 cells showed no effect on tumor growth, although both exosomes should have similar tumor antigens. Exosomes bearing both tumor antigens and the M. tuberculosis antigen (or their epitopes) have a high potential as a candidate for cancer vaccine to overcome the immune escape by tumor cells.
Complex clinical outcomes, such as adverse reaction to vaccination, arise from the concerted interactions among the myriad components of a biological system. Therefore, comprehensive etiological models can be developed only through the integrated study of multiple types of experi...
Talwar, G P; Diwan, M; Razvi, F; Malhotra, R
Vast changes are taking place in vaccinology consequent to the introduction of new technologies. Amongst the vaccines included in the Expanded Programme of Immunization (EPI), the pertussis vaccine has been replaced by acellular purified fractions devoid of side-effects. Non-pathogenic but immunogenic mutants of tetanus and diptheria toxins are likely to replace the toxoids. An effective vaccine against hepatitis B prepared by recombinant technology is in large-scale use. Conjugated vaccines against Haemophilus influenzae b, S. pneumococcus and meningococcus are now available, as also vaccines against mumps, rubella and measles. Combination vaccines have been devised to limit the number of injections. Vaccine delivery systems have been developed to deliver multiple doses of the vaccine at a single contact point. A genetically-engineered oral vaccine for typhoid imparts better and longer duration of immunity. Oral vaccines for cholera and other enteric infections are under clinical trials. The nose as a route for immunization is showing promise for mucosal immunity and for anti-inflammatory experimental vaccines against multiple sclerosis and insulin-dependent diabetes mellitus. The range of vaccines has expanded to include pathogens resident in the body such as Helicobacter pylori (duodenal ulcer), S. mutans (dental caries), and human papilloma virus (carcinoma of the cervix). An important progress is the recognition that DNA alone can constitute the vaccines, inducing both humoral and cell-mediated immune responses. A large number of DNA vaccines have been made and shown interesting results in experimental animals. Live recombinant vaccines against rabies and rinderpest have proven to be highly effective for controlling these infections in the field, and those for AIDS are under clinical trial. Potent adjuvants have added to the efficacy of the vaccines. New technologies have emerged to 'humanize' mouse monoclonals by genetic engineering and express these
Alexander W. Tarr
Full Text Available In the 26 years since the discovery of Hepatitis C virus (HCV a major global research effort has illuminated many aspects of the viral life cycle, facilitating the development of targeted antivirals. Recently, effective direct-acting antiviral (DAA regimens with >90% cure rates have become available for treatment of chronic HCV infection in developed nations, representing a significant advance towards global eradication. However, the high cost of these treatments results in highly restricted access in developing nations, where the disease burden is greatest. Additionally, the largely asymptomatic nature of infection facilitates continued transmission in at risk groups and resource constrained settings due to limited surveillance. Consequently a prophylactic vaccine is much needed. The HCV envelope glycoproteins E1 and E2 are located on the surface of viral lipid envelope, facilitate viral entry and are the targets for host immunity, in addition to other functions. Unfortunately, the extreme global genetic and antigenic diversity exhibited by the HCV glycoproteins represents a significant obstacle to vaccine development. Here we review current knowledge of HCV envelope protein structure, integrating knowledge of genetic, antigenic and functional diversity to inform rational immunogen design.
Issa, Mohammad Nouh; Ashhab, Yaqoub
Brucella melitensis Rev.1 is an avirulent strain that is widely used as a live vaccine to control brucellosis in small ruminants. Although an assembled draft version of Rev.1 genome has been available since 2009, this genome has not been investigated to characterize this important vaccine. In the present work, we used the draft genome of Rev.1 to perform a thorough genomic comparison and sequence analysis to identify and characterize the panel of its unique genetic markers. The draft genome of Rev.1 was compared with genome sequences of 36 different Brucella melitensis strains from the Brucella project of the Broad Institute of MIT and Harvard. The comparative analyses revealed 32 genetic alterations (30 SNPs, 1 single-bp insertion and 1 single-bp deletion) that are exclusively present in the Rev.1 genome. In silico analyses showed that 9 out of the 17 non-synonymous mutations are deleterious. Three ABC transporters are among the disrupted genes that can be linked to virulence attenuation. Out of the 32 mutations, 11 Rev.1 specific markers were selected to test their potential to discriminate Rev.1 using a bi-directional allele-specific PCR assay. Six markers were able to distinguish between Rev.1 and a set of control strains. We succeeded in identifying a panel of 32 genome-specific markers of the B. melitensis Rev.1 vaccine strain. Extensive in silico analysis showed that a considerable number of these mutations could severely affect the function of the associated genes. In addition, some of the discovered markers were able to discriminate Rev.1 strain from a group of control strains using practical PCR tests that can be applied in resource-limited settings. Copyright © 2016 Elsevier Ltd. All rights reserved.
David J. Dowling
Full Text Available Background. Group B Neisseria meningitidis, an endotoxin-producing gram-negative bacterium, causes the highest incidence of group B meningococcus (MenB disease in the first year of life. The Bexsero vaccine is indicated in Europe from 8 weeks of age. Endotoxin components of outer membrane vesicles (OMVs or soluble lipopolysaccharide (LPS represent a potential source of inflammation and residual reactogenicity. The purpose of this study was to compare novel candidate MenB vaccine formulations with licensed vaccines, including Bexsero, using age-specific in vitro culture systems.Methods. OMVs from wild type and inactivated lpxL1 gene mutant N. meningitidis strains were characterized in human neonatal and adult in vitro whole blood assays and dendritic cell arrays. OMVs were benchmarked against licensed vaccines, including Bexsero and whole cell pertussis formulations, with respect to Th-polarizing cytokine and PGE2 production, as well as cell surface activation markers (HLA-DR, CD86, CCR7. OMV immunogenicity was assessed in mice.Results. ΔlpxLI native OMVs demonstrated significantly less cytokine induction in human blood and DCs than Bexsero and most of the other pediatric vaccines (e.g., PedvaxHib, EasyFive, Bacillus Calmette–Guérin (BCG tested. Despite a much lower inflammatory profile in vitro than Bexsero, ΔlpxLI native OMVs still had moderate DC maturing ability and induced robust anti-N. meningitidis antibody responses after murine immunization.Conclusions. A meningococcal vaccine comprised of attenuated LPS-based OMVs with a limited inflammatory profile in vitro induces robust antigen-specific immunogenicity in vivo.
Zemp, Franz; Rajwani, Jahanara; Mahoney, Douglas J
The family Rhabdoviridae (RV) comprises a large, genetically diverse collection of single-stranded, negative sense RNA viruses from the order Mononegavirales. Several RV members are being developed as live-attenuated vaccine vectors for the prevention or treatment of infectious disease and cancer. These include the prototype recombinant Vesicular Stomatitis Virus (rVSV) and the more recently developed recombinant Maraba Virus, both species within the genus Vesiculoviridae. A relatively strong safety profile in humans, robust immunogenicity and genetic malleability are key features that make the RV family attractive vaccine platforms. Currently, the rVSV vector is in preclinical development for vaccination against numerous high-priority infectious diseases, with clinical evaluation underway for HIV/AIDS and Ebola virus disease. Indeed, the success of the rVSV-ZEBOV vaccine during the 2014-15 Ebola virus outbreak in West Africa highlights the therapeutic potential of rVSV as a vaccine vector for acute, life-threatening viral illnesses. The rVSV and rMaraba platforms are also being tested as 'oncolytic' cancer vaccines in a series of phase 1-2 clinical trials, after being proven effective at eliciting immune-mediated tumour regression in preclinical mouse models. In this review, we discuss the biological and genetic features that make RVs attractive vaccine platforms and the development and ongoing testing of rVSV and rMaraba strains as vaccine vectors for infectious disease and cancer.
Ojima, Toshiyasu; Iwahashi, Makoto; Nakamura, Masaki; Matsuda, Kenji; Nakamori, Mikihito; Ueda, Kentaro; Naka, Teiji; Katsuda, Masahiro; Miyazawa, Motoki; Yamaue, Hiroki
Granulocyte macrophage colony-stimulating factor (GM-CSF) is a key cytokine for the generation and stimulation of dendritic cells (DCs), and it may also play a pivotal role in promoting the survival of DCs. In this study, the feasibility of creating a cancer vaccine using DCs adenovirally transduced with the carcinoembryonic antigen (CEA) gene and the GM-CSF gene was examined. In addition, the effect of the co-transduction of GM-CSF gene on the lifespan of these genetically modified DCs was determined. A cytotoxic assay using peripheral blood mononuclear cell (PBMC)-derived cytotoxic T lymphocytes (CTLs) was performed in a 4-h 51Cr release assay. The apoptosis of DCs was examined by TdT-mediated dUTP-FITC nick end labeling (TUNEL) assay. CEA-specific CTLs were generated from PBMCs stimulated with genetically modified DCs expressing CEA. The cytotoxicity of these CTLs was augmented by co-transduction of DCs with the GM-CSF gene. Co-transduction of the GM-CSF gene into DCs inhibited apoptosis of these DCs themselves via up-regulation of Bcl-x(L) expression, leading to the extension of the lifespan of these DCs. Furthermore, the transduction of the GM-CSF gene into DCs also suppressed the incidence of apoptosis of DCs induced by transforming growth factor-beta1 (TGFbeta-1). Immunotherapy using these genetically modified DCs may therefore be useful with several advantages as follows: i) adenoviral toxicity to DCs can be reduced; ii) the lifespan of vaccinated DCs can be prolonged; and iii) GM-CSF may protect DCs from apoptosis induced by tumor-derived TGFbeta-1 in the regional lymph nodes.
van Ballegooijen, W. Marijn; van Houdt, Robin; Bruisten, Sylvia M.; Boot, Hein J.; Coutinho, Roel A.; Wallinga, Jacco
The effect of vaccination programs on transmission of infectious disease is usually assessed by monitoring programs that rely on notifications of symptomatic illness. For monitoring of infectious diseases with a high proportion of asymptomatic cases or a low reporting rate, molecular sequence data
Wang, Xiaoping; Lin, Huanping; Wang, Qiaoxia
Purposes: To construct a recombinant vaccine alpha-fetoprotein (AFP)-heat shock protein (HSP70) complex, and study its ability to induce specific CTL response and its protective effect against AFP-producing tumor. Material/Methods: A recombinant vaccine was constructed by conjugating mouse alpha-fetoprotein to heat shock protein 70. By way of intracutaneous injection, mice were primed and boosted with recombinant vaccine mAFP/HSP70, whereas single mAFP or HSP70 injection as controls. The ELISPOT and ELISA were used to measure the frequency of cells producing the cytokine IFN-γ in splenocytes and the level of anti-AFP antibody of serum from immunized mice respectively. In vivo tumor challenge were carried out to assess the immune effect of the recombinant vaccine. Results: By recombinant mAFP/HSP70 vaccine immunization, the results of ELISPOT and ELISA showed that the number of splenic cells producing IFN-γ and the level of anti-AFP antibody of serum were significantly higher in mAFP/HSP70 group than those in mAFP and HSP70 groups (108.50±11.70 IFN-γ spots/106 cells vs 41.60±10.40 IFN-γ spots/106 cells, 7.32±3.14 IFN-γ spots/106 cells, P<0.01; 156.32±10.42 μg/mL vs 66.52±7.35 μg/mL, 5.73±2.89 μg/mL, P<0.01). The tumor volume in mAFP/HSP70 group was significantly smaller than that in mAFP and HSP70 groups (42.44±7.14 mm3 vs 392.23±12.46 mm3, 838.63±13.84 mm3, P<0.01). Conclusions: The study further confirmed the function of heat shock protein 70's immune adjuvant. Sequential immunization with recombinant mAFP/HSP70 vaccine could generate effective antitumor immunity on AFP-producing tumor. The recombined mAFP/HSP70 vaccine may be suitable for serving as an immunotherapy for hepatocellular carcinoma.
Salaheldin, Ahmed H; Veits, Jutta; Abd El-Hamid, Hatem S; Harder, Timm C; Devrishov, Davud; Mettenleiter, Thomas C; Hafez, Hafez M; Abdelwhab, Elsayed M
Vaccination of poultry to control highly pathogenic avian influenza virus (HPAIV) H5N1 is used in several countries. HPAIV H5N1 of clade 2.2.1 which is endemic in Egypt has diversified into two genetic clades. Clade 22.214.171.124 represents antigenic drift variants in vaccinated commercial poultry while clade 126.96.36.199 variants are detected in humans and backyard poultry. Little is known about H5N1 infection in vaccinated turkeys under field conditions. Here, we describe an HPAI H5N1 outbreak in a vaccinated meat-turkey flock in Egypt. Birds were vaccinated with inactivated H5N2 and H5N1 vaccines at 8 and 34 days of age, respectively. At 72 nd day of age (38 days post last vaccination), turkeys exhibited mild respiratory signs, cyanosis of snood and severe congestion of the internal organs. Survivors had a reduction in feed consumption and body gain. A mortality of ~29% cumulated within 10 days after the onset of clinical signs. Laboratory diagnosis using RT-qPCRs revealed presence of H5N1 but was negative for H7 and H9 subtypes. A substantial antigenic drift against different serum samples from clade 188.8.131.52 and clade 184.108.40.206 was observed. Based on full genome sequence analysis the virus belonged to clade 220.127.116.11 but clustered with recent H5N1 viruses from 2015 in poultry in Israel, Gaza and Egypt in a novel subclade designated here 18.104.22.168a which is distinct from 2014/2015 22.214.171.124 viruses. These viruses possess 126.96.36.199 clade-specific genetic signatures and also mutations in the HA similar to those in clade 188.8.131.52 that enabled evasion from humoral immune response. Taken together, this manuscript describes a recent HPAI H5N1 outbreak in vaccinated meat-turkeys in Egypt after infection with a virus representing novel distinct 184.108.40.206a subclade. Infection with HPAIV H5N1 in commercial turkeys resulted in significant morbidity and mortality despite of vaccination using H5 vaccines. The isolated virus showed antigenic drift and clustered in a novel cluster designated here
Several evidences were presented during the meeting in London entitled "Origins of AIDS and the HIV epidemic," debating the idea that AIDS was an accidental result of a polio vaccination campaign conducted by a virologist, Hilary Koprowski, and colleagues in the late 1950s among thousands of people in the Belgian Congo. The meeting carefully examined the CHAT theory presented by a writer, Edward Hooper, in his book "The River" and has raised questions on the correlation between vaccination sites and early records of HIV-1, and on the estimated amount of HIV particles that would get through each stage of the process of creating CHAT. Overall, the meeting agreed to reject the CHAT theory of AIDS for it has no basis, since Koprowski and colleagues denied the use of chimpanzee kidneys, which Hooper openly suggests in his book. The meeting noted that the disease's origins remain a mystery.
Full Text Available Here we describe a prime-boost regimen of vaccination in Macaca fascicularis that combines priming with novel anionic microspheres designed to deliver the biologically active HIV-1 Tat protein and boosting with Tat in Alum. This regimen of immunization modulated the IgG subclass profile and elicited a balanced Th1-Th2 type of humoral and cellular responses. Remarkably, following intravenous challenge with SHIV89.6Pcy243, vaccinees significantly blunted acute viremia, as compared to control monkeys, and this control was associated with significantly lower CD4+ T cell depletion rate during the acute phase of infection and higher ability to resume the CD4+ T cell counts in the post-acute and chronic phases of infection. The long lasting control of viremia was associated with the persistence of high titers anti-Tat antibodies whose profile clearly distinguished vaccinees in controllers and viremics. Controllers, as opposed to vaccinated and viremic cynos, exhibited significantly higher pre-challenge antibody responses to peptides spanning the glutamine-rich and the RGD-integrin-binding regions of Tat. Finally, among vaccinees, titers of anti-Tat IgG1, IgG3 and IgG4 subclasses had a significant association with control of viremia in the acute and post-acute phases of infection. Altogether these findings indicate that the Tat/H1D/Alum regimen of immunization holds promise for next generation vaccines with Tat protein or other proteins for which maintenance of the native conformation and activity are critical for optimal immunogenicity. Our results also provide novel information on the role of anti-Tat responses in the prevention of HIV pathogenesis and for the design of new vaccine candidates.
Daniell, Henry; Chan, Hui-Ting; Pasoreck, Elise K
Plastid-made biopharmaceuticals treat major metabolic or genetic disorders, including Alzheimer's, diabetes, hypertension, hemophilia, and retinopathy. Booster vaccines made in chloroplasts prevent global infectious diseases, such as tuberculosis, malaria, cholera, and polio, and biological threats, such as anthrax and plague. Recent advances in this field include commercial-scale production of human therapeutic proteins in FDA-approved cGMP facilities, development of tags to deliver protein drugs to targeted human cells or tissues, methods to deliver precise doses, and long-term stability of protein drugs at ambient temperature, maintaining their efficacy. Codon optimization utilizing valuable information from sequenced chloroplast genomes enhanced expression of eukaryotic human or viral genes in chloroplasts and offered unique insights into translation in chloroplasts. Support from major biopharmaceutical companies, development of hydroponic production systems, and evaluation by regulatory agencies, including the CDC, FDA, and USDA, augur well for advancing this novel concept to the clinic and revolutionizing affordable healthcare.
Yee, Pinn Tsin Isabel; Laa Poh, Chit
Enterovirus-A71 (EV-A71) is an etiological agent of the hand, foot and mouth disease (HFMD). EV-A71 infection produces high fever and ulcers in children. Some EV-A71 strains produce severe infections leading to pulmonary edema and death. Although the protective efficacy of the inactivated vaccine (IV) was ≥90% against mild HFMD, there was approximately 80% protection against severe HFMD. The monovalent EV-A71 IV elicits humoral immunity but lacks long-term immunogenicity. Spontaneous mutations of the EV-A71 genome could lead to antigenicity changes and the virus may not be neutralized by antibodies elicited by the IV. A better alternative would be the live attenuated vaccine (LAV) that elicits cellular and humoral immunity. The LAV induces excellent antigenicity and chances of reversion is reduced by presence of multiple mutations which could reduce pathogenicity. Besides CV-A16, outbreaks have been caused by CV-A6 and CV-A10, hence the development of bivalent and trivalent vaccines is required. Copyright © 2017 Elsevier Inc. All rights reserved.
Moyo, Sabrina J.; Blomberg, Bjørn; Hanevik, Kurt; Kommedal, Oyvind; Vainio, Kirsti; Maselle, Samuel Y.; Langeland, Nina
Background Tanzania currently rolls out vaccination against rotavirus-diarrhea, a major cause of child illness and death. As the vaccine covers a limited number of rotavirus variants, this study describes the molecular epidemiology of rotavirus among children under two years in Dar es Salaam, Tanzania, prior to implementation of vaccination. Methods Stool specimens, demographic and clinical information, were collected from 690 children admitted to hospital due to diarrhea (cases) and 545 children without diarrhea (controls) during one year. Controls were inpatient or children attending child health clinics. Rotavirus antigen was detected using ELISA and positive samples were typed by multiplex semi-nested PCR and sequencing. Results The prevalence of rotavirus was higher in cases (32.5%) than in controls (7.7%, Protavirus prevalence was higher in cool (23.9%) than hot months (17.1%) of the year (P = 0.012). We also observed significant seasonal variation of G genotypes. Rotavirus was most frequently found in the age group of four to six months. The prevalence of rotavirus in cases was lower in stunted children (28.9%) than in non-stunted children (40.1%, P = 0.003) and lower in HIV-infected (15.4%, 4/26) than in HIV-uninfected children (55.3%, 42/76, PRotavirus infection and circulating genotypes showed seasonal variation. This study also suggests that rotavirus may not be an opportunistic pathogen in children infected with HIV. PMID:24844631
Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs and genes that exhibit presence/absence variation have provided informative marker sets for bacterial and viral genotyping. Identification of marker sets optimised for these purposes has been based on maximal generalized discriminatory power as measured by Simpson's Index of Diversity, or on the ability to identify specific variants. Here we describe the Not-N algorithm, which is designed to identify small sets of genetic markers diagnostic for user-specified subsets of known genetic variants. The algorithm does not treat the user-specified subset and the remaining genetic variants equally. Rather Not-N analysis is designed to underpin assays that provide 0% false negatives, which is very important for e.g. diagnostic procedures for clinically significant subgroups within microbial species. Results The Not-N algorithm has been incorporated into the "Minimum SNPs" computer program and used to derive genetic markers diagnostic for multilocus sequence typing-defined clonal complexes, hepatitis C virus (HCV subtypes, and phylogenetic clades defined by comparative genome hybridization (CGH data for Campylobacter jejuni, Yersinia enterocolitica and Clostridium difficile. Conclusion Not-N analysis is effective for identifying small sets of genetic markers diagnostic for microbial sub-groups. The best results to date have been obtained with CGH data from several bacterial species, and HCV sequence data.
Cacao (Theobroma cacao L.), the tree from which cocoa butter and chocolate is derived, is conserved in field genebanks. The largest of these ex situ collections in the public domain is the International Cocoa Genebank, Trinidad (ICG,T). Reduction of genetic redundancy is essential to improve the acc...
Lehner, Thomas; Hoelscher, Michael; Clerici, Mario; Gotch, Frances; Pedneault, Louise; Tartaglia, Jim; Gray, Clive; Mestecky, Jiri; Sattentau, Quentin; van de Wijgert, Janneke; Toure, Coumba; Osmanov, Saladin; Schmidt, Reinold E.; Debre, Patrice; Romaris, Manuel; Hoeveler, Arnd; Di Fabio, Simonetta
The European Commission (EC) has strong commitments and recognises the need to continue to ensure that HIV/AIDS research efforts receive global attention. The EC is facing this challenge in a global context and has made substantial investments together with European Developing Countries Clinical
Jesse D Deere
Full Text Available Despite tremendous progress in our understanding of human immunodeficiency virus (HIV natural history and advances in HIV treatment, there is neither an approved vaccine nor a cure for infection. Here, we describe the development and characterization of a novel replicating vaccine vector utilizing Cytomegalovirus (CMV and a TLR5 adjuvant. After partial truncation of the central, immunodominant hypervariable domain, flagellin (fliC from Salmonella was cloned downstream of a codon optimized gag gene from simian immunodeficiency virus (SIV and transiently expressed in telomerized rhesus fibroblast (TeloRF cells in culture. Lysates generated from these transfected cells induced the tumor necrosis factor alpha (TNF-α, in a mouse macrophage cell line, in a TLR5-dependent manner. The Gag/FliC expression construct was cloned into a bacterial artificial chromosome encoding the rhesus CMV (RhCMV genome, and infectious RhCMV was generated following transfection of TeloRF cells. This virus stably expressed an SIV Gag/FliC fusion protein through four serial passages. Lysates generated from infected cells induced TNF-α in a TLR5-dependent manner. Western blot analysis of infected cell lysates verified expression of a Gag/FliC fusion protein using a SIV p27 capsid monoclonal antibody. Lastly, rhesus macaques inoculated with this novel RhCMV virus demonstrated increased inflammatory responses at the site of inoculation seven days post-infection when compared to the parental RhCMV. These results demonstrate that an artificially constructed replicating RhCMV expressing an SIV Gag/FliC fusion protein is capable of activating TLR5 in a macrophage cell line in vitro and induction of an altered inflammatory response in vivo. Ongoing animals studies are aimed at determining vaccine efficacy, including subsequent challenge with pathogenic SIV.
Guerrero, Rubén D.; Arango, Carlos A.; Reyes, Andrés
We propose a methodology to design optimal pulses for achieving quantum optimal control on molecular systems. Our approach constrains pulse shapes to linear combinations of a fixed number of experimentally relevant pulse functions. Quantum optimal control is obtained by maximizing a multi-target fitness function using genetic algorithms. As a first application of the methodology, we generated an optimal pulse that successfully maximized the yield on a selected dissociation channel of a diatomic molecule. Our pulse is obtained as a linear combination of linearly chirped pulse functions. Data recorded along the evolution of the genetic algorithm contained important information regarding the interplay between radiative and diabatic processes. We performed a principal component analysis on these data to retrieve the most relevant processes along the optimal path. Our proposed methodology could be useful for performing quantum optimal control on more complex systems by employing a wider variety of pulse shape functions
Guerrero, Rubén D., E-mail: email@example.com [Department of Physics, Universidad Nacional de Colombia, Bogota (Colombia); Arango, Carlos A. [Department of Chemical Sciences, Universidad Icesi, Cali (Colombia); Reyes, Andrés [Department of Chemistry, Universidad Nacional de Colombia, Bogota (Colombia)
We propose a methodology to design optimal pulses for achieving quantum optimal control on molecular systems. Our approach constrains pulse shapes to linear combinations of a fixed number of experimentally relevant pulse functions. Quantum optimal control is obtained by maximizing a multi-target fitness function using genetic algorithms. As a first application of the methodology, we generated an optimal pulse that successfully maximized the yield on a selected dissociation channel of a diatomic molecule. Our pulse is obtained as a linear combination of linearly chirped pulse functions. Data recorded along the evolution of the genetic algorithm contained important information regarding the interplay between radiative and diabatic processes. We performed a principal component analysis on these data to retrieve the most relevant processes along the optimal path. Our proposed methodology could be useful for performing quantum optimal control on more complex systems by employing a wider variety of pulse shape functions.
... Influenza Types Seasonal Avian Swine Variant Pandemic Other HIV/AIDS and the Flu Questions & Answers Language: English ( ... people with HIV and AIDS. Should people with HIV/AIDS receive the inactivated influenza vaccine? People with ...
Rijn, van P.A.; Water, van de S.G.P.; Gennip, van H.G.P.
Bluetongue virus (BTV) includes 24 serotypes and recently even more serotypes are proposed. Mass vaccination campaigns highlight the need for differential diagnostics in vaccinated populations. Bluetongue disease is routinely diagnosed by serological and virological tests by which differentiation
Iredale, R.; Rapport, F.; Sivell, S.; Jones, W.; Edwards, A.; Gray, J.; Elwyn, G.
RATIONALE: Patients concerned about a family history of breast cancer can face difficult decisions about screening, prophylactic surgery and genetic testing. Decision aids can facilitate patient decision making and currently include leaflets and computerized tools. These are largely aimed at the
Full Text Available Chickens lack the retinoic acid-inducible gene I (RIG-I and sense avian influenza virus (AIV infections by means of the melanoma differentiation-associated gene 5 product (chMDA5. Plasmid-driven expression of the N-terminal half of chMDA5 containing the caspase activation and recruitment domains [chMDA5(1-483] triggers interferon-β responses in chicken cells. We hypothesized that mimicking virus infection by chMDA5(1-483 expression may enhance vaccine-induced adaptive immunity. In order to test this, the potential genetic adjuvant properties of chMDA5(1-483 were evaluated in vivo in combination with a suboptimal quantity of a plasmid DNA vaccine expressing haemagglutinin (HA of H5N1 AIV. Co-administration of the HA plasmid with plasmid DNA for chMDA5(1-483 expression resulted in approximately 10-fold higher HA-specific antibody responses than injection of the HA plasmid mixed with empty vector DNA as control. Accordingly, compared with HA DNA vaccination alone, the chMDA5(1-483-adjuvanted HA DNA vaccine mediated enhanced protection against a lethal H5N1 challenge infection in chickens, with reduced clinical signs and cloacal virus shedding. These data demonstrate that innate immune activation by expression of signaling domains of RIG-I-like receptors can be exploited to enhance vaccine efficacy.
Younan, Patrick; Kowalski, John; Kiem, Hans-Peter
The combination of genetic modification and hematopoietic stem cell (HSC) transplantation may provide the necessary means to develop an alternative treatment option to conventional antiretroviral therapy. As HSCs give rise to all hematopoietic cell types susceptible to HIV infection, modification of HSCs is an ideal strategy for the development of infection-resistant immune cell populations. Although promising results have been obtained in multiple animal models, additional evidence is needed to convincingly demonstrate the feasibility of this approach as a treatment of HIV-1 infected patients. Here, we review the potential of HSC transplantation and the recently identified limitations of this approach. Using the Berlin Patient as a model for a functional cure, we contrast the confines of autologous versus allogeneic transplantation. Finally, we suggest that although autologous, gene-modified HSC-transplantation may significantly reduce plasma viremia, reaching the lower detection limits currently obtainable through daily HAART will remain a challenging endeavor that will require innovative combinatorial therapies.
Full Text Available The combination of genetic modification and hematopoietic stem cell (HSC transplantation may provide the necessary means to develop an alternative treatment option to conventional antiretroviral therapy. As HSCs give rise to all hematopoietic cell types susceptible to HIV infection, modification of HSCs is an ideal strategy for the development of infection-resistant immune cell populations. Although promising results have been obtained in multiple animal models, additional evidence is needed to convincingly demonstrate the feasibility of this approach as a treatment of HIV-1 infected patients. Here, we review the potential of HSC transplantation and the recently identified limitations of this approach. Using the Berlin Patient as a model for a functional cure, we contrast the confines of autologous versus allogeneic transplantation. Finally, we suggest that although autologous, gene-modified HSC-transplantation may significantly reduce plasma viremia, reaching the lower detection limits currently obtainable through daily HAART will remain a challenging endeavor that will require innovative combinatorial therapies.
Bubeník, Jan; Šímová, Jana
Roč. 14, č. 1 (2009), s. 169-173 ISSN 1107-0625 R&D Projects: GA ČR GA301/06/0774; GA ČR GA301/07/1410 EU Projects: European Commission(XE) 18933 - CLINIGENE Institutional research plan: CEZ:AV0Z50520514 Keywords : residual tumour disease * HPV16 * cellular vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.600, year: 2009
Zagury, J F; Sill, A; Blattner, W; Lachgar, A; Le Buanec, H; Richardson, M; Rappaport, J; Hendel, H; Bizzini, B; Gringeri, A; Carcagno, M; Criscuolo, M; Burny, A; Gallo, R C; Zagury, D
To investigate which immune parameters, such as antibodies against HIV-1 specificities, or viral parameters, such as p24 antigenemia, are predictive of disease progression. We performed studies on serum collected from individuals exhibiting two extremes of disease evolution--67 fast progressors (FP) and 182 nonprogressors (NP)--at their enrollment. After a 1- to 2-year clinical follow-up of 104 nonprogressors after their enrollment, we could determine the best serologic predictors for disease progression. We investigated levels of antibodies to tetanus toxoid and to HIV antigens including Env, Gag, Nef, and Tat proteins, as well as p24 antigenemia, viremia, CD4 cell count, and interferon-alpha (IFN-alpha) titers in FPs and NPs, and we correlated these data with clinical and biologic signs of progression. p24 Antigenemia, a marker of viral replication, and anti-Tat antibodies were highly and inversely correlated in both groups (P < .001). Furthermore, anti-p24 antibodies and low serum IFN-alpha levels were correlated to the NP versus the FP cohort. Finally, among NPs, only antibodies to Tat and not to the other HIV specificities (Env, Nef, Gag) were significantly predictive of clinical stability during their follow-up. Antibodies toward HIV-1 Tat, which are inversely correlated to p24 antigenemia, appear as a critical marker for a lack of disease progression. This study strongly suggests that rising anti-Tat antibodies through active immunization may be beneficial in AIDS vaccine development to control viral replication.
MacLennan, Calman A.; Saul, Allan
With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented. PMID:25136089
Xu, Wanhong; Zhang, Zhidong; Nfon, Charles; Yang, Ming
Foot-and-mouth disease serotype O viruses (FMDV/O) are responsible for the most outbreaks in FMD endemic countries. O1/BFS is one of the recommended FMD/O vaccine strains by World Reference Laboratory for FMD. In the current study, FMDV/O1 BFS vaccine strain and serotype O field isolates (45) were analyzed phylogenetically and antigenically to gain more insight into the genetic and antigenic characteristics of the vaccine strain and field isolates. O1/BFS showed similarity with 89% of the field isolates using a virus neutralization test (VNT). The P1 region encoding the FMDV capsid was sequenced and analysed for 46 strains of FMDV/O. Phylogenetic analysis showed these viruses originated from five continents and covered eight of 11 reported topotypes. Five isolates that demonstrated low antigenic similarities with O1/BFS were analyzed for their antigenic variation at the known neutralizing antigenic sites. Three of the five isolates demonstrated unique amino acid substitutions at various antigenic sites. No unique amino acid substitutions were observed for the other two unmatched isolates. Positively selected residues were identified on the surface of the FMD virus capsid supporting that it is important to continuously monitor field isolates for their antigenic and phenotypic changes. In conclusion, the vaccine strain O1/BFS is likely to confer protection against 89% of the 45 FMDV/O isolates based on VNT. Thus O1/BFS vaccine strain is still suitable for use in global FMD serotype O outbreak control. Combining data from phylogenetic, molecular and antigenic analysis can provide improvements in the process of vaccine selection. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.
Mazurowski, Maciej A; Habas, Piotr A; Zurada, Jacek M; Tourassi, Georgia D
This paper presents an optimization framework for improving case-based computer-aided decision (CB-CAD) systems. The underlying hypothesis of the study is that each example in the knowledge database of a medical decision support system has different importance in the decision making process. A new decision algorithm incorporating an importance weight for each example is proposed to account for these differences. The search for the best set of importance weights is defined as an optimization problem and a genetic algorithm is employed to solve it. The optimization process is tailored to maximize the system's performance according to clinically relevant evaluation criteria. The study was performed using a CAD system developed for the classification of regions of interests (ROIs) in mammograms as depicting masses or normal tissue. The system was constructed and evaluated using a dataset of ROIs extracted from the Digital Database for Screening Mammography (DDSM). Experimental results show that, according to receiver operator characteristic (ROC) analysis, the proposed method significantly improves the overall performance of the CAD system as well as its average specificity for high breast mass detection rates
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Hossein Ghayoumi Zadeh
Full Text Available Background: Breast cancer is one of the most prevalent cancers among women today. The importance of breast cancer screening, its role in the timely identification of patients, and the reduction in treatment expenses are considered to be among the highest sanitary priorities of a modern country. Thermal imaging clearly possesses a special role in this stage due to rapid diagnosis and use of harmless rays.Methods: We used a thermal camera for imaging of the patients. Important parameters were derived from the images for their posterior analysis with the aid of a genetic algorithm. The principal components that were entered in a fuzzy neural network for clustering breast cancer were identified.Results: The number of images considered for the test included a database of 200 patients out of whom 15 were diagnosed with breast cancer via mammography. Results of the base method show a sensitivity of 93%. The selection of parameters in the combination module gave rise measured errors, which in training of the fuzzy-neural network were of the order of clustering 1.0923×10-5, which reached 2%.Conclusion: The study indicates that thermal image scanning coupled with the presented method based on artificial intelligence can possess a special status in screening women for breast cancer due to the use of harmless non-radiation rays. There are cases where physicians cannot decisively say that the observed pattern in theimage is benign or malignant. In such cases, the response of the computer model can be a valuable support tool for the physician enabling an accurate diagnosis based on the type of imaging pattern as a response from the computer model.
Sahiner, Berkman; Chan, Heang-Ping; Petrick, Nicholas; Helvie, Mark A.; Goodsitt, Mitchell M.
A genetic algorithm (GA) based feature selection method was developed for the design of high-sensitivity classifiers, which were tailored to yield high sensitivity with high specificity. The fitness function of the GA was based on the receiver operating characteristic (ROC) partial area index, which is defined as the average specificity above a given sensitivity threshold. The designed GA evolved towards the selection of feature combinations which yielded high specificity in the high-sensitivity region of the ROC curve, regardless of the performance at low sensitivity. This is a desirable quality of a classifier used for breast lesion characterization, since the focus in breast lesion characterization is to diagnose correctly as many benign lesions as possible without missing malignancies. The high-sensitivity classifier, formulated as the Fisher's linear discriminant using GA-selected feature variables, was employed to classify 255 biopsy-proven mammographic masses as malignant or benign. The mammograms were digitized at a pixel size of 0.1mmx0.1mm, and regions of interest (ROIs) containing the biopsied masses were extracted by an experienced radiologist. A recently developed image transformation technique, referred to as the rubber-band straightening transform, was applied to the ROIs. Texture features extracted from the spatial grey-level dependence and run-length statistics matrices of the transformed ROIs were used to distinguish malignant and benign masses. The classification accuracy of the high-sensitivity classifier was compared with that of linear discriminant analysis with stepwise feature selection (LDA sfs ). With proper GA training, the ROC partial area of the high-sensitivity classifier above a true-positive fraction of 0.95 was significantly larger than that of LDA sfs , although the latter provided a higher total area (A z ) under the ROC curve. By setting an appropriate decision threshold, the high-sensitivity classifier and LDA sfs correctly
Reimann, Ilona; Blome, Sandra; Beer, Martin
Chimeric pestiviruses have shown great potential as marker vaccine candidates against pestiviral infections. Exemplarily, we describe here the construction and testing of the most promising classical swine fever vaccine candidate "CP7_E2alf" in detail. The description is focused on classical cloning technologies in combination with reverse genetics.
Ting-Yu Angela Liao
Full Text Available Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.
Liao, Ting-Yu Angela; Lau, Alice; Joseph, Sunil; Hytönen, Vesa; Hmama, Zakaria
Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb) antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.
Stryjewska, Agnieszka; Kiepura, Katarzyna; Librowski, Tadeusz; Lochyński, Stanisław
Monoclonal antibodies, modern vaccines and gene therapy have become a major field in modern biotechnology, especially in the area of human health and fascinating developments achieved in the past decades are impressive examples of an interdisciplinary interplay between medicine, biology and engineering. Among the classical products from cells one can find viral vaccines, monoclonal antibodies, and interferons, as well as recombinant therapeutic proteins. Gene therapy opens up challenging new areas. In this review, a definitions of these processes are given and fields of application and products, as well as the future prospects, are discussed.
An international colloquium on AIDS held near Paris from October 26-28, 1989, unlike the World Conference on AIDS in Montreal the year before, was able to find reasons for optimism. Significant progress was reported in immunotherapy and in chemotherapy. Successful experiments in vaccinating monkeys against the AIDS virus were reported from the US, France, and Zaire. Time is needed to prove the efficacy of the vaccines because of the slow development in AIDS. A vaccine is being tested by Jonas Salk and collaborators in 75 seropositive volunteers who do not yet show full blown disease but who have very low levels of T4 lymphocytes. Plans are underway for a larger test on 500 seropositive patients at different stages of infection. According to Salk, the new chemical and logical approach toward AIDS will allow combinations of immunotherapy and chemotherapy to destroy the virus. R. Gallo of France listed as accomplishments of the past year a better understanding of the virus, improved case management techniques, increased ability to control Kaposi's sarcoma, considerable progress in the search for a vaccine, and detection of immune proteins that affect the virus. New biological markers permit establishment of correlations between cellular modifications and the progress of the disease as well as the precise effects of treatment. The new immune system drugs immuthiol and DDI are expected to reach the market soon. Patients very soon will be able to receive less toxic alternative treatments, which can be combined for greater efficacy once their toxic interactions are understood.
Leuenberger, Mona; Frigerio, Simona; Wild, Peter J; Noetzli, Franziska; Korol, Dimitri; Zimmermann, Dieter R; Gengler, Carole; Probst-Hensch, Nicole M; Moch, Holger; Tinguely, Marianne
The biological behavior of chronic lymphocytic leukemia and small lymphocytic lymphoma is unpredictable. Nonetheless, non-mutated IgV(H) gene rearrangement, ATM (11q22-23) and p53 (17p13) deletion are recognized as unfavorable prognosticators in chronic lymphocytic leukemia. The mRNA expression of activation-induced cytidine deaminase (AID), an enzyme indispensable for somatic hypermutation processes, was claimed to be predictive of non-mutated chronic lymphocytic leukemia cells in blood. Here, we evaluated AID protein expression compared with known molecular and immunohistochemical prognostic indicators in 71 chronic lymphocytic leukemia/small lymphocytic lymphoma patients using a tissue microarray approach. We found AID heterogeneously expressed in tumor cells as shown by colocalization analysis for CD5 and CD23. Ki-67 positive paraimmunoblasts of the proliferation centers displayed the highest expression. This observation is reflected by a significant association of AID positivity with a high proliferation rate (P=0.012). ATM deletion was detected in 10% (6/63) of patients and p53 deletion in 19% (13/67) of patients. Moreover, both ATM (P=0.002) and p53 deletion (P=0.004) were significantly associated with AID. IgV(H) gene mutation was seen in 45% (27/60) of patients. Twenty-five percent (17/69) of patients with AID-positive chronic lymphocytic leukemia/small lymphocytic lymphoma displayed a shorter survival than AID-negative chronic lymphocytic leukemia/small lymphocytic lymphoma patients (61 vs 130 months, P=0.001). Although there was a trend, we could not show an association with the IgV(H) gene mutation status. Taken together, our study shows that AID expression is an indicator of an unfavorable prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma patients, although it is not a surrogate marker for the IgV(H) status. Furthermore, the microenvironment of proliferation centers seems to influence AID regulation and might be an initiating factor
Joosten, H.; Strunk, A. L. M.; Meijer, S.; Boers, J. E.; Aries, M.J.H.; Abbes, A. P.; Engel, H.; Beukhof, J. R.
Several genetic disorders can present in adult patients with renal insufficiency. Genetic renal disease other than ADPKD accounts for ESRD in 3% of the adult Dutch population. Because of this low prevalence and their clinical heterogeneity most adult nephrologists are less familiar with these
MuŽíková, G; Laga, R
Vaccines have helped considerably in eliminating some life-threatening infectious diseases in past two hundred years. Recently, human medicine has focused on vaccination against some of the world's most common infectious diseases (AIDS, malaria, tuberculosis, etc.), and vaccination is also gaining popularity in the treatment of cancer or autoimmune diseases. The major limitation of current vaccines lies in their poor ability to generate a sufficient level of protective antibodies and T cell responses against diseases such as HIV, malaria, tuberculosis and cancers. Among the promising vaccination systems that could improve the potency of weakly immunogenic vaccines belong macromolecular carriers (water soluble polymers, polymer particels, micelles, gels etc.) conjugated with antigens and immunistumulatory molecules. The size, architecture, and the composition of the high molecular-weight carrier can significantly improve the vaccine efficiency. This review includes the most recently developed (bio)polymer-based vaccines reported in the literature.
Waterbeemd, van de B.; Streefland, M.; Ley, de P.; Zomer, B.; Dijken, van H.; Martens, D.E.; Wijffels, R.H.; Pol, van der L.A.
The use of detergent-extracted outer membrane vesicles (OMVs) is an established approach for development of a multivalent PorA vaccine against N. meningitidis serogroup B. Selective removal of lipopolysaccharide (LPS) decreases toxicity, but promotes aggregation and narrows the immune response.
Šímová, Jana; Reiniš, Milan; Sobota, Vesna; Čapková, Jana; Bubeník, Jan; Jandlová, Táňa
Roč. 46, č. 1 (2000), s. 11-16 ISSN 0015-5500 R&D Projects: GA MZd NC5526; GA MZd NC4501; GA ČR GA312/98/0826; GA ČR GA312/99/0542 Institutional research plan: CEZ:AV0Z5052915 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.351, year: 2000
Limou, Sophie; Coulonges, Cédric; Herbeck, Joshua T.; van Manen, Daniëlle; An, Ping; Le Clerc, Sigrid; Delaneau, Olivier; Diop, Gora; Taing, Lieng; Montes, Matthieu; van't Wout, Angélique B.; Gottlieb, Geoffrey S.; Therwath, Amu; Rouzioux, Christine; Delfraissy, Jean-François; Lelièvre, Jean-Daniel; Lévy, Yves; Hercberg, Serge; Dina, Christian; Phair, John; Donfield, Sharyne; Goedert, James J.; Buchbinder, Susan; Estaquier, Jérôme; Schächter, François; Gut, Ivo; Froguel, Philippe; Mullins, James I.; Schuitemaker, Hanneke; Winkler, Cheryl; Zagury, Jean-François
Background. The compilation of previous genomewide association studies of AIDS shows a major polymorphism in the HCP5 gene associated with both control of the viral load and long-term nonprogression (LTNP) to AIDS. Methods. To look for genetic variants that affect LTNP without necessary control of the viral load, we reanalyzed the genomewide data of the unique LTNP Genomics of Resistance to Immunodeficiency Virus (GRIV) cohort by excluding “elite controller” patients, who were controlling the viral load at very low levels (<100 copies/mL). Results. The rs2234358 polymorphism in the CXCR6 gene was the strongest signal (P = 2.5 × 10−7; odds ratio, 1.85) obtained for the genomewide association study comparing the 186 GRIV LTNPs who were not elite controllers with 697 uninfected control subjects. This association was replicated in 3 additional independent European studies, reaching genomewide significance of Pcombined = 9.7 × 10−10. This association with LTNP is independent of the combined CCR2-CCR5 locus and the HCP5 polymorphisms. Conclusion. The statistical significance, the replication, and the magnitude of the association demonstrate that CXCR6 is likely involved in the molecular etiology of AIDS and, in particular, in LTNP, emphasizing the power of extreme-phenotype cohorts. CXCR6 is a chemokine receptor that is known as a minor coreceptor in human immunodeficiency virus type 1 infection but could participate in disease progression through its role as a mediator of inflammation. PMID:20704485
Gilbert, M Thomas P; Rambaut, Andrew; Wlasiuk, Gabriela
HIV-1 group M subtype B was the first HIV discovered and is the predominant variant of AIDS virus in most countries outside of sub-Saharan Africa. However, the circumstances of its origin and emergence remain unresolved. Here we propose a geographic sequence and time line for the origin of subtype...... B and the emergence of pandemic HIV/AIDS out of Africa. Using HIV-1 gene sequences recovered from archival samples from some of the earliest known Haitian AIDS patients, we find that subtype B likely moved from Africa to Haiti in or around 1966 (1962-1970) and then spread there for some years before...... HIV/AIDS epidemic outside sub-Saharan Africa and the most genetically diverse subtype B epidemic, which might present challenges for HIV-1 vaccine design and testing. The emergence of the pandemic variant of subtype B was an important turning point in the history of AIDS, but its spread was likely...
Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...
Full Text Available Anti-cancer DNA vaccines have attracted growing interest as a simple and non-invasive method for both the treatment and prevention of tumors induced by human papillomaviruses. Nonetheless, the low immunogenicity of parenterally administered vaccines, particularly regarding the activation of cytotoxic CD8+ T cell responses, suggests that further improvements in both vaccine composition and administration routes are still required. In the present study, we report the immune responses and anti-tumor effects of a DNA vaccine (pgD-E7E6E5 expressing three proteins (E7, E6, and E5 of the human papillomavirus type 16 genetically fused to the glycoprotein D of the human herpes simplex virus type 1, which was administered to mice by the intradermal (id route using a gene gun. A single id dose of pgD-E7E6E5 (2 µg/dose induced a strong activation of E7-specific interferon-γ (INF-γ-producing CD8+ T cells and full prophylactic anti-tumor effects in the vaccinated mice. Three vaccine doses inhibited tumor growth in 70% of the mice with established tumors. In addition, a single vaccine dose consisting of the co-administration of pgD-E7E6E5 and the vector encoding interleukin-12 or granulocyte-macrophage colony-stimulating factor further enhanced the therapeutic anti-tumor effects and conferred protection to 60 and 50% of the vaccinated mice, respectively. In conclusion, id administration of pgD-E7E6E5 significantly enhanced the immunogenicity and anti-tumor effects of the DNA vaccine, representing a promising administration route for future clinical trials.
Whole genome characterization of a novel porcine reproductive and respiratory syndrome virus 1 isolate: Genetic evidence for recombination between Amervac vaccine and circulating strains in mainland China.
Chen, Nanhua; Liu, Qiaorong; Qiao, Mingming; Deng, Xiaoyu; Chen, Xizhao; Sun, Ming
Genotype 1 porcine reproductive and respiratory syndrome virus (PRRSV 1) have been continuously isolated in China in recent years. Complete genome sequences of these isolates are important to investigate the prevalence and evolution of Chinese PRRSV 1. Herein, we describe the isolation of a novel PRRSV 1 isolate, denominated HLJB1, in the Heilongjiang province of China. Complete genome sequencing of HLJB1 showed that it shares 90.66% and 58.21% nucleotide identities with PRRSV 1 and 2 prototypic strains Lelystad virus and ATCC VR-2332, respectively. HLJB1 has a unique 5-amino-acid insertion in nsp2, which has never been described in other PRRSV 1 isolates. Whole genome-based phylogenetic analysis revealed that all Chinese PRRSV 1 isolates are clustered in pan-European subtype 1 and can be divided into four subgroups. HLJB1 resides in the subgroup of BJEU06-1-like isolates but is also closely related to the Amervac-like isolates. Additionally, recombination analyses suggested that HLJB1 is a recombinant from the Amervac vaccine and the BJEU06-1 isolate. To our best knowledge, our results provide the first genetic evidence for recombination between Amervac vaccine and circulating strains. These findings are also beneficial for studying the origin and evolution of PRRSV 1 in China. Copyright © 2017. Published by Elsevier B.V.
Pruna, Dario; Balestri, Paolo; Zamponi, Nelia; Grosso, Salvatore; Gobbi, Giuseppe; Romeo, Antonino; Franzoni, Emilio; Osti, Maria; Capovilla, Giuseppe; Longhi, Riccardo; Verrotti, Alberto
Reports of childhood epilepsies in temporal association with vaccination have had a great impact on the acceptance of vaccination programs by health care providers, but little is known about this possible temporal association and about the types of seizures following vaccinations. For these reasons the Italian League Against Epilepsy (LICE), in collaboration with other Italian scientific societies, has decided to generate Guidelines on Vaccinations and Epilepsy. The aim of Guidelines on Vaccinations and Epilepsy is to present recent unequivocal evidence from published reports on the possible relationship between vaccines and epilepsy in order to provide information about contraindications and risks of vaccinations in patients with epilepsy. The following main issues have been addressed: (1) whether contraindications to vaccinations exist in patients with febrile convulsions, epilepsy, and/or epileptic encephalopathies; and (2) whether any vaccinations can cause febrile seizures, epilepsy, and/or epileptic encephalopathies. Diphtheria-tetanus-pertussis (DTP) vaccination and measles, mumps, and rubella vaccination (MMR) increase significantly the risk of febrile seizures. Recent observations and data about the relationships between vaccination and epileptic encephalopathy show that some cases of apparent vaccine-induced encephalopathy could in fact be caused by an inherent genetic defect with no causal relationship with vaccination. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.
Lauro Ferreira da Silva Pinto Neto
Full Text Available This cross-sectional study assessed the immunization status of human immune deficiency virus (HIV-infected patients receiving care at an outpatient clinic in Brazil. The sociodemographic characteristics, CD4 count and HIV viral load of 281 out of 612 adult outpatients were analyzed. A total of 331 patients were excluded because of no availability of vaccination cards. Chi-square or Fisher's exact test were used. Immunization coverage was higher for diphtheria/tetanus (59.79% and hepatitis B (56.7%, and lowest for hepatitis A (6.8% and for meningococcal group C (6%. Only 11.74% of the patients had received the influenza virus vaccine yearly since their HIV-infection diagnosis. No vaccination against influenza (p < 0.034 or hepatitis B (p < 0.029 were associated with CD4 counts <500 cells/mL; no vaccination against flu or pneumococcus were associated with detectable HIV viral load (p < 0.049 and p < 0.002, respectively. Immunization coverage is still very low among HIV-infected adults in this setting despite recommendations and high infection-related mortality.
Ram Vinay Pandey
Full Text Available Traditional Sanger sequencing as well as Next-Generation Sequencing have been used for the identification of disease causing mutations in human molecular research. The majority of currently available tools are developed for research and explorative purposes and often do not provide a complete, efficient, one-stop solution. As the focus of currently developed tools is mainly on NGS data analysis, no integrative solution for the analysis of Sanger data is provided and consequently a one-stop solution to analyze reads from both sequencing platforms is not available. We have therefore developed a new pipeline called MutAid to analyze and interpret raw sequencing data produced by Sanger or several NGS sequencing platforms. It performs format conversion, base calling, quality trimming, filtering, read mapping, variant calling, variant annotation and analysis of Sanger and NGS data under a single platform. It is capable of analyzing reads from multiple patients in a single run to create a list of potential disease causing base substitutions as well as insertions and deletions. MutAid has been developed for expert and non-expert users and supports four sequencing platforms including Sanger, Illumina, 454 and Ion Torrent. Furthermore, for NGS data analysis, five read mappers including BWA, TMAP, Bowtie, Bowtie2 and GSNAP and four variant callers including GATK-HaplotypeCaller, SAMTOOLS, Freebayes and VarScan2 pipelines are supported. MutAid is freely available at https://sourceforge.net/projects/mutaid.
Pandey, Ram Vinay; Pabinger, Stephan; Kriegner, Albert; Weinhäusel, Andreas
Traditional Sanger sequencing as well as Next-Generation Sequencing have been used for the identification of disease causing mutations in human molecular research. The majority of currently available tools are developed for research and explorative purposes and often do not provide a complete, efficient, one-stop solution. As the focus of currently developed tools is mainly on NGS data analysis, no integrative solution for the analysis of Sanger data is provided and consequently a one-stop solution to analyze reads from both sequencing platforms is not available. We have therefore developed a new pipeline called MutAid to analyze and interpret raw sequencing data produced by Sanger or several NGS sequencing platforms. It performs format conversion, base calling, quality trimming, filtering, read mapping, variant calling, variant annotation and analysis of Sanger and NGS data under a single platform. It is capable of analyzing reads from multiple patients in a single run to create a list of potential disease causing base substitutions as well as insertions and deletions. MutAid has been developed for expert and non-expert users and supports four sequencing platforms including Sanger, Illumina, 454 and Ion Torrent. Furthermore, for NGS data analysis, five read mappers including BWA, TMAP, Bowtie, Bowtie2 and GSNAP and four variant callers including GATK-HaplotypeCaller, SAMTOOLS, Freebayes and VarScan2 pipelines are supported. MutAid is freely available at https://sourceforge.net/projects/mutaid.
Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by the ...
Full Text Available Neosporosis, caused by the apicomplexan parasite Neospora caninum, represents one of the economically most important causes of abortion in cattle. During pregnancy, the parasite infects the placental tissue and the fetus, which can lead to stillbirth, abortion, or birth of weak calves. Alternatively, calves are born without clinical symptoms, but they can carry over the parasite to the next generation. In addition, N. caninum causes neuromuscular disease in dogs. The economic importance of neosporosis has prompted researchers to invest in the development of measures to prevent infection of cattle by vaccination. A good vaccine must stimulate protective cellular immune responses as well as antibody responses at mucosal sites and, systemically, must activate T-helper cells to produce relevant cytokines, and must elicit specific antibodies that aid in limiting parasite proliferation, e.g., by interference with host cell invasion, activation of complement, and/or opsonization of parasites to have them killed by macrophages. Different types of vaccines have been investigated, either in bovines or in the mouse model. These include live vaccines such as naturally less virulent isolates of N. caninum, attenuated strains generated by irradiation or chemical means, or genetically modified transgenic strains. Live vaccines were shown to be very effective; however, there are serious disadvantages in terms of safety, costs of production, and stability of the final product. Subunit vaccines have been intensively studied, as they would have clear advantages such as reduced costs in production, processing and storage, increased stability and shelf life. The parasite antigens involved in adhesion and invasion of host cells, such as surface constituents, microneme-, rhoptry- and dense granule-components represent interesting targets. Subunit vaccines have been applied as bacterially expressed recombinant antigens or as DNA vaccines. Besides monovalent vaccines
Ding, Pan; Gong, Xue-Qing
Titanium dioxide (TiO2) is an important metal oxide that has been used in many different applications. TiO2 has also been widely employed as a model system to study basic processes and reactions in surface chemistry and heterogeneous catalysis. In this work, we investigated the (011) surface of rutile TiO2 by focusing on its reconstruction. Density functional theory calculations aided by a genetic algorithm based optimization scheme were performed to extensively sample the potential energy surfaces of reconstructed rutile TiO2 structures that obey (2 × 1) periodicity. A lot of stable surface configurations were located, including the global-minimum configuration that was proposed previously. The wide variety of surface structures determined through the calculations performed in this work provide insight into the relationship between the atomic configuration of a surface and its stability. More importantly, several analytical schemes were proposed and tested to gauge the differences and similarities among various surface structures, aiding the construction of the complete pathway for the reconstruction process.
Progress is reported on the following research projects: genetic effects of high LET radiations; genetic regulation, alteration, and repair; chromosome replication and the division cycle of Escherichia coli; effects of radioisotope decay in the DNA of microorganisms; initiation and termination of DNA replication in Bacillus subtilis; mutagenesis in mouse myeloma cells; lethal and mutagenic effects of near-uv radiation; effect of 8-methoxypsoralen on photodynamic lethality and mutagenicity in Escherichia coli; DNA repair of the lethal effects of far-uv; and near uv irradiation of bacterial cells
Christensen, Kaare; McGue, Matt
The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...
Oram, Richard A; Patel, Kashyap; Hill, Anita; Shields, Beverley; McDonald, Timothy J; Jones, Angus; Hattersley, Andrew T; Weedon, Michael N
With rising obesity, it is becoming increasingly difficult to distinguish between type 1 diabetes (T1D) and type 2 diabetes (T2D) in young adults. There has been substantial recent progress in identifying the contribution of common genetic variants to T1D and T2D. We aimed to determine whether a score generated from common genetic variants could be used to discriminate between T1D and T2D and also to predict severe insulin deficiency in young adults with diabetes. We developed genetic risk scores (GRSs) from published T1D- and T2D-associated variants. We first tested whether the scores could distinguish clinically defined T1D and T2D from the Wellcome Trust Case Control Consortium (WTCCC) (n = 3,887). We then assessed whether the T1D GRS correctly classified young adults (diagnosed at 20-40 years of age, the age-group with the most diagnostic difficulty in clinical practice; n = 223) who progressed to severe insulin deficiency 0.280 (>50th centile in those with T1D) is indicative of T1D (50% sensitivity, 95% specificity). A low T1D GRS (young adults with diabetes, T1D GRS alone predicted progression to insulin deficiency (AUC 0.87 [95% CI 0.82-0.92]; P young adults with diabetes who will require insulin treatment. This will be an important addition to correctly classifying individuals with diabetes when clinical features and autoimmune markers are equivocal. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Baker, David P.; Collins, John M.; Leon, Juan
Numerous epidemiological studies from the early years of the tragic HIV and AIDS pandemic in sub-Saharan Africa identified formal education as a risk factor increasing the chance of infection. Instead of playing its usual role as a preventative factor, as has been noted in many other public health cases, until the mid-1990s educated African men…
Bubeník, Jan; Vonka, V.; Šímová, Jana; Rössner ml., Pavel
Roč. 2, Suppl. 1 (1998), s. 117 ISSN 1107-3756. [World Congress on Advances in Oncology /3./ and International Symposium on Molecular Medicine /1./. 15.10.1998-17.10.1998, Island of Crete] Subject RIV: EB - Genetics ; Molecular Biology
of development. Food vaccines may also help to suppress autoimmunity disorders such as Type-1. Diabetes. Key words: Edible vaccines, oral vaccines, antigen expression, food vaccines. INTRODUCTION. Vaccination involves the stimulation of the immune system to prepare it for the event of an invasion from a particular ...
... During Pregnancy Frequently Asked Questions about Vaccine Recalls Historical Vaccine Safety Concerns FAQs about GBS and Menactra ... CISA Resources for Healthcare Professionals Evaluation Current Studies Historical Background 2001-12 Publications Technical Reports Vaccine Safety ...
Barmpalexis, Panagiotis; Grypioti, Agni; Eleftheriadis, Georgios K; Fatouros, Dimitris G
In the present study, liquisolid formulations were developed for improving dissolution profile of aprepitant (APT) in a solid dosage form. Experimental studies were complemented with artificial neural networks and genetic programming. Specifically, the type and concentration of liquid vehicle was evaluated through saturation-solubility studies, while the effect of the amount of viscosity increasing agent (HPMC), the type of wetting (Soluplus® vs. PVP) and solubilizing (Poloxamer®407 vs. Kolliphor®ELP) agents, and the ratio of solid coating (microcrystalline cellulose) to carrier (colloidal silicon dioxide) were evaluated based on in vitro drug release studies. The optimum liquisolid formulation exhibited improved dissolution characteristics compared to the marketed product Emend®. X-ray diffraction (XRD), scanning electron microscopy (SEM) and a novel method combining particle size analysis by dynamic light scattering (DLS) and HPLC, revealed that the increase in dissolution rate of APT in the optimum liquisolid formulation was due to the formation of stable APT nanocrystals. Differential scanning calorimetry (DSC) and attenuated total reflection FTIR spectroscopy (ATR-FTIR) revealed the presence of intermolecular interactions between APT and liquisolid formulation excipients. Multilinear regression analysis (MLR), artificial neural networks (ANNs), and genetic programming (GP) were used to correlate several formulation variables with dissolution profile parameters (Y 15min and Y 30min ) using a full factorial experimental design. Results showed increased correlation efficacy for ANNs and GP (RMSE of 0.151 and 0.273, respectively) compared to MLR (RMSE = 0.413).
Krystal Teasley Hamorsky
Full Text Available INTRODUCTION: Cholera toxin B subunit (CTB is a component of an internationally licensed oral cholera vaccine. The protein induces neutralizing antibodies against the holotoxin, the virulence factor responsible for severe diarrhea. A field clinical trial has suggested that the addition of CTB to killed whole-cell bacteria provides superior short-term protection to whole-cell-only vaccines; however, challenges in CTB biomanufacturing (i.e., cost and scale hamper its implementation to mass vaccination in developing countries. To provide a potential solution to this issue, we developed a rapid, robust, and scalable CTB production system in plants. METHODOLOGY/PRINCIPAL FINDINGS: In a preliminary study of expressing original CTB in transgenic Nicotiana benthamiana, the protein was N-glycosylated with plant-specific glycans. Thus, an aglycosylated CTB variant (pCTB was created and overexpressed via a plant virus vector. Upon additional transgene engineering for retention in the endoplasmic reticulum and optimization of a secretory signal, the yield of pCTB was dramatically improved, reaching >1 g per kg of fresh leaf material. The protein was efficiently purified by simple two-step chromatography. The GM1-ganglioside binding capacity and conformational stability of pCTB were virtually identical to the bacteria-derived original B subunit, as demonstrated in competitive enzyme-linked immunosorbent assay, surface plasmon resonance, and fluorescence-based thermal shift assay. Mammalian cell surface-binding was corroborated by immunofluorescence and flow cytometry. pCTB exhibited strong oral immunogenicity in mice, inducing significant levels of CTB-specific intestinal antibodies that persisted over 6 months. Moreover, these antibodies effectively neutralized the cholera holotoxin in vitro. CONCLUSIONS/SIGNIFICANCE: Taken together, these results demonstrated that pCTB has robust producibility in Nicotiana plants and retains most, if not all, of major
Reumkens, Kelly; Tummers, Marly H E; Gietel-Habets, Joyce J G; van Kuijk, Sander M J; Aalfs, Cora M; van Asperen, Christi J; Ausems, Margreet G E M; Collée, Margriet; Dommering, Charlotte J; Kets, C Marleen; van der Kolk, Lizet E; Oosterwijk, Jan C; Tjan-Heijnen, Vivianne C G; van der Weijden, Trudy; de Die-Smulders, Christine E M; van Osch, Liesbeth A D M
An online decision aid to support persons having a genetic predisposition to cancer and their partners during reproductive decision-making was developed. A two-phase usability test was conducted among 12 couples (N = 22; 2 persons participated without their partner) at risk for hereditary cancer and 15 health care providers. Couples and health care providers expressed similar suggestions for improvements, and evaluated the modified decision aid as acceptable, easy to use, and comprehensible. The final decision aid was pilot tested (N = 16) with paired sample t tests comparing main outcomes (decisional conflict, knowledge, realistic expectations regarding the reproductive options and decision self-efficacy) before (T0), immediately (T1) and 2 weeks after (T2) use of the decision aid. Pilot testing indicated decreased decisional conflict scores, increased knowledge, and improved realistic expectations regarding the reproductive options, at T1 and T2. No effect was found for couples' decision self-efficacy. The positive findings during usability testing were thus reflected in the pilot study. The decision aid will be further evaluated in a nationwide pretest-posttest study to facilitate implementation in the onco-genetic counselling setting. Ultimately, it is expected that the decision aid will enable end-users to make an informed decision.
... Vaccine Safety Vaccines Work Vaccine Types Vaccine Ingredients Vaccines by Disease Chickenpox ... Typhoid Fever Whooping Cough (Pertussis) Yellow Fever Who and When Infants, Children, and Teens ...
Piso, B; Wild, C
Looking across boarders reveals that the national immunization programs of various countries differ in their vaccination schedules and decisions regarding the implementation and funding of new vaccines. The aim of this review is to identify decision aids and crucial criteria for a rational decision-making process on vaccine introduction and to develop a theoretical framework for decision-making based on available literature. Systematic literature search supplemented by hand-search. We identified five published decision aids for vaccine introduction and program planning in industrialized countries. Their comparison revealed an overall similarity with some differences in the approach as well as criteria. Burden of disease and vaccine characteristics play a key role in all decision aids, but authors vary in their views on the significance of cost-effectiveness analyses. Other relevant factors that should be considered before vaccine introduction are discussed to highly differing extents. These factors include the immunization program itself as well as its conformity with other programs, its feasibility, acceptability, and equity, as well as ethical, legal and political considerations. Assuming that the most comprehensive framework possible will not provide a feasible tool for decision-makers, we suggest a stepwise procedure. Though even the best rational approach and most comprehensive evaluation is limited by remaining uncertainties, frameworks provide at least a structured approach to evaluate the various aspects of vaccine implementation decision-making. This process is essential in making consistently sound decisions and will facilitate the public's confidence in the decision and its realization.
This initiative supports phases 2 and 3 clinical trials of an experimental Ebola vaccine. The experimental vaccine is based on an attenuated recombinant Vesicular Stomatitis Virus vector (VSV-EBOV). The Public Health Agency of Canada developed the vaccine and licensed it to NewLink Genetics and Merck. Early vaccine ...
Nay, Karah; Hoopes, Karl
This is a flip chart type booklet with first aid information for horses, including checking vitals, pulse rate, respiration, mucus membrane color and capillary refill, signs of colic, deworming, vaccinations recommended for Utah, hoof care, and dental care.
González-Romo, Fernando; Picazo, Juan J
Recent and important advances in the fields of immunology, genomics, functional genomics, immunogenetics, immunogenomics, bioinformatics, microbiology, genetic engineering, systems biology, synthetic biochemistry, proteomics, metabolomics and nanotechnology, among others, have led to new approaches in the development of vaccines. The better identification of ideal epitopes, the strengthening of the immune response due to new adjuvants, and the search of new routes of vaccine administration, are good examples of advances that are already a reality and that will favour the development of more vaccines, their use in indicated population groups, or its production at a lower cost. There are currently more than 130 vaccines are under development against the more wished (malaria or HIV), difficult to get (CMV or RSV), severe re-emerging (Dengue or Ebola), increasing importance (Chagas disease or Leishmania), and nosocomial emerging (Clostridium difficile or Staphylococcus aureus) infectious diseases. Copyright © 2015. Published by Elsevier España, S.L.U.
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.
Kakinami, Lisa; Newman, Peter A.; Lee, Sung-Jae; Duan, Naihua
The development of safe and efficacious preventive HIV vaccines offers the best long-term hope of controlling the AIDS pandemic. Nevertheless, suboptimal uptake of safe and efficacious vaccines that already exist suggest that HIV vaccine acceptability cannot be assumed, particularly among communities most vulnerable to HIV. The present study aimed to identify barriers and motivators to future HIV vaccine acceptability among low socioeconomic, ethnically diverse men and women in Los Angeles County. Participants completed a cross-sectional survey assessing their attitudes and beliefs regarding future HIV vaccines. Hypothetical HIV vaccine scenarios were administered to determine HIV vaccine acceptability. Two-sided t-tests were performed, stratified by gender, to examine the association between vaccine acceptability and potential barriers and motivators. Barriers to HIV vaccine acceptability differed between men and women. For women, barriers to HIV vaccine acceptability were related to their intimate relationships (p Motivators for women included the ability to conceive a child without worrying about contracting HIV (p Motivators for men included feeling safer with sex partners (p motivator for both men and women (p <0.10). Gender-specific interventions may increase vaccine acceptability among men and women at elevated risk for HIV infection. Among women, interventions need to focus on addressing barriers due to gendered power dynamics in relationships and discrimination in health care. Among men, education that addresses fears and misconceptions about adverse effects of HIV vaccination on health and the importance of vaccination as one component of integrated HIV prevention may increase vaccine acceptability. PMID:18484322
Ogholikhan, Sina; Schwarz, Kathleen B.
Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B ...
Kalveram, Birte; Lihoradova, Olga; Indran, Sabarish V; Ikegami, Tetsuro
Rift Valley fever virus (RVFV), which causes hemorrhagic fever, neurological disorders or blindness in humans, and a high rate abortion and fetal malformation in ruminants, has been classified as a HHS/USDA overlap select agent and a risk group 3 pathogen. It belongs to the genus Phlebovirus in the family Bunyaviridae and is one of the most virulent members of this family. Several reverse genetics systems for the RVFV MP-12 vaccine strain as well as wild-type RVFV strains, including ZH548 and ZH501, have been developed since 2006. The MP-12 strain (which is a risk group 2 pathogen and a non-select agent) is highly attenuated by several mutations in its M- and L-segments, but still carries virulent S-segment RNA, which encodes a functional virulence factor, NSs. The rMP12-C13type (C13type) carrying 69% in-frame deletion of NSs ORF lacks all the known NSs functions, while it replicates as efficient as does MP-12 in VeroE6 cells lacking type-I IFN. NSs induces a shut-off of host transcription including interferon (IFN)-beta mRNA and promotes degradation of double-stranded RNA-dependent protein kinase (PKR) at the post-translational level. IFN-beta is transcriptionally upregulated by interferon regulatory factor 3 (IRF-3), NF-kB and activator protein-1 (AP-1), and the binding of IFN-beta to IFN-alpha/beta receptor (IFNAR) stimulates the transcription of IFN-alpha genes or other interferon stimulated genes (ISGs), which induces host antiviral activities, whereas host transcription suppression including IFN-beta gene by NSs prevents the gene upregulations of those ISGs in response to viral replication although IRF-3, NF-kB and activator protein-1 (AP-1) can be activated by RVFV7. Thus, NSs is an excellent target to further attenuate MP-12, and to enhance host innate immune responses by abolishing the IFN-beta suppression function. Here, we describe a protocol for generating a recombinant MP-12 encoding mutated NSs, and provide an example of a screening method to identify
Canada's international response to the HIV/AIDS epidemic is largely built around the work of the Canadian HIV Vaccine Initiative (CHVI). CHVI proposes to increase the capacity of Canada and low- and middle-income countries to respond to the HIV/AIDS pandemic by developing new HIV vaccines and other preventive ...
Ferreira, T B; Alves, P M; Aunins, J G; Carrondo, M J T
Vaccines are the most effective and inexpensive prophylactic tool in veterinary medicine. Ideally, vaccines should induce a lifelong protective immunity against the target pathogen while not causing clinical or pathological signs of diseases in the vaccinated animals. However, such ideal vaccines are rare in the veterinary field. Many vaccines are either of limited effectiveness or have harmful side effects. In addition, there are still severe diseases with no effective vaccines. A very important criterion for an ideal vaccine in veterinary medicine is low cost; this is especially important in developing countries and even more so for poultry vaccination, where vaccines must sell for a few cents a dose. Traditional approaches include inactivated vaccines, attenuated live vaccines and subunit vaccines. Recently, genetic engineering has been applied to design new, improved vaccines. Adenovirus vectors are highly efficient for gene transfer in a broad spectrum of cell types and species. Moreover, adenoviruses often induce humoral, mucosal and cellular immune responses to antigens encoded by the inserted foreign genes. Thus, adenoviruses have become a vector of choice for delivery and expression of foreign proteins for vaccination. Consequently, the market requirements for adenovirus vaccines are increasing, creating a need for production methodologies of concentrated vectors with warranted purity and efficacy. This review summarizes recent developments and approaches of adenovirus production and purification as the application of these vectors, including successes and failures in clinical applications to date.
Clinton, Chelsea; Sridhar, Devi
In this report we assess who pays for cooperation in global health through an analysis of the financial flows of WHO, the World Bank, the Global Fund to Fight HIV/AIDS, TB and Malaria, and Gavi, the Vaccine Alliance. The past few decades have seen the consolidation of influence in the disproportionate roles the USA, UK, and the Bill & Melinda Gates Foundation have had in financing three of these four institutions. Current financing flows in all four case study institutions allow donors to finance and deliver assistance in ways that they can more closely control and monitor at every stage. We highlight three major trends in global health governance more broadly that relate to this development: towards more discretionary funding and away from core or longer-term funding; towards defined multi-stakeholder governance and away from traditional government-centred representation and decision-making; and towards narrower mandates or problem-focused vertical initiatives and away from broader systemic goals. Copyright © 2017 Elsevier Ltd. All rights reserved.
Aubert, M; Aumaître, H; Beytout, J; Bloch, K; Bouhour, D; Callamand, P; Chave, C; Cheymol, J; Combadière, B; Dahlab, A; Denis, F; De Pontual, L; Dodet, B; Dommergues, M-A; Dufour, V; Gagneur, A; Gaillat, J; Gaudelus, J; Gavazzi, G; Gillet, Y; Gras-le-Guen, C; Haas, H; Hanslik, T; Hau-Rainsard, I; Larnaudie, S; Launay, O; Lorrot, M; Loulergue, P; Malvy, D; Marchand, S; Picherot, G; Pinquier, D; Pulcini, C; Rabaud, C; Regnier, F; Reinert, P; Sana, C; Savagner, C; Soubeyrand, B; Stephan, J-L; Strady, C
The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve - but for how long ? - the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine
Yen, Catherine; Tate, Jacqueline E; Hyde, Terri B; Cortese, Margaret M; Lopman, Benjamin A; Jiang, Baoming; Glass, Roger I; Parashar, Umesh D
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
Cremers, Amelieke J H; Mobegi, Fredrick M; de Jonge, Marien I; van Hijum, Sacha A F T; Meis, Jacques F; Hermans, Peter W M; Ferwerda, Gerben; Bentley, Stephen D; Zomer, Aldert L
The 7-valent pneumococcal conjugated vaccine (PCV7) has affected the genetic population of Streptococcus pneumoniae in pediatric carriage. Little is known however about pneumococcal population genomics in adult invasive pneumococcal disease (IPD) under vaccine pressure. We sequenced and serotyped
Jacobson, Robert M; St Sauver, Jennifer L; Finney Rutten, Lila J
Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
Barrett, A D
Although there are approximately 68 flaviviruses recognized, vaccines have been developed to control very few human flavivirus diseases. Licensed live attenuated vaccines have been developed for yellow fever (strain 17D) and Japanese encephalitis (strain SA14-14-2) viruses, and inactivated vaccines have been developed for Japanese encephalitis and tick-borne encephalitis viruses. The yellow fever live attenuated 17D vaccine is one of the most efficacious and safe vaccines developed to date and has been used to immunize more than 300 million people. A number of experimental vaccines are being developed, most notably for dengue. Candidate tetravalent live attenuated dengue vaccines are undergoing clinical trials. Other vaccines are being developed using reverse genetics, DNA vaccines, and recombinant immunogens. In addition, the yellow fever 17D vaccine has been used as a backbone to generate chimeric viruses containing the premembrane and envelope protein genes from other flaviviruses. The "Chimerivax" platform has been used to construct chimeric Japanese encephalitis and dengue viruses that are in different phases of development. Similar strategies are being used by other laboratories.
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.
Improved humoral and cellular immune response against the gp120 V3 loop of HIV-1 following genetic immunization with a chimeric DNA vaccine encoding the V3 inserted into the hepatites B surface antigen
Fomsgaard, A.; Nielsen, H.V.; Bryder, K.
response and a uniform strong anti-HBs CTL response already 1 week p.i. in all mice. DNA vaccination with the chimeric MN V2/HBsAg plasmid elicited humoral responses against both viruses within 3-6 weeks which peaked at 6-12 weeks and remained stable for at least 25 weeks. In addition, specific CTL...... responses were induced in all mice against both MN V3 and HBsAg already within the first 3 weeks, lasting at least 11 weeks. Thus, HBsAg acts as a `genetic vaccine adjuvant' augmenting and accelerating the cellular and humoral immune response against the inserted MN V3 loop. Such chimeric HIV-HbsAg plasmid...
Improved humoral and cellular immune responses against the gp120 V3 loop of HIV-1 following genetic immunization with a chimeric DNA vaccine encoding the V3 inserted into the hepatitis B surface antigen
Fomsgaard, A; Nielsen, H V; Bryder, K
response and a uniform strong anti-HBs CTL response already 1 week p.i. in all mice. DNA vaccination with the chimeric MN V3/HBsAg plasmid elicited humoral responses against both viruses within 3-6 weeks which peaked at 6-12 weeks and remained stable for at least 25 weeks. In addition, specific CTL...... responses were induced in all mice against both MN V3 and HBsAg already within the first 3 weeks, lasting at least 11 weeks. Thus, HBsAg acts as a 'genetic vaccine adjuvant' augmenting and accelerating the cellular and humoral immune response against the inserted MN V3 loop. Such chimeric HIV-HBsAg plasmid...
L.E. Duijzer (Evelot); W.L. van Jaarsveld (Willem); J. Wallinga (Jacco); R. Dekker (Rommert)
textabstractFor a large number of infectious diseases, vaccination is the most effective way to prevent an epidemic. However, the vaccine stockpile is hardly ever sufficient to treat the entire population, which brings about the challenge of vaccine allocation. To aid decision makers facing this
Full Text Available HIV infection and AIDS is increasingly becoming a major public health problem in our country. Currently, the reported cases represent only the 'tip of the iceberg' of the problem. In view of the fact that no cure or vaccine for the disease has yet been found, spreading knowledge and removing misconceptions is about the only way that AIDS can be effectively tackled.This handbook, developed by Prof. Shankar Chowdhury and associates, seeks to address all levels of medical and non-medical AIDS workers, as well as the layman. It deals with topics ranging from biology of the virus, symptoms and transmission of disease, to prevention, counselling for infected persons and action plan for AIDS education.The biology of the virus and the immune system is described in simple terms, as well as methods of testing for HIV, and what these test results mean. The progression of disease in adults and children, development of symptoms, diagnostic criteria for AIDS, treatment and outcome of disease is dealt with. How AIDS spreads between people, and the health risk for health workers and families is examined. The various ways in which transmission of HIV can be prevented is looked at in detail, including public health measures, national and internatonal action, and ethical and human rights issues involved.
Verdier, Francois; Barrow, Paul C.; Burge, Joeelle
Vaccines play a major role in the prevention of human birth defects by protecting the pregnant woman from teratogenic or otherwise harmful infections. Until now, it has not been common practice to perform preclinical developmental toxicity tests for new vaccines. Despite the excellent safety record of vaccines, increased attention is now being given to the feasibility of screening new vaccines for developmental hazards in animals before their use in humans. Contrary to previous assumptions, many vaccines are now given to potentially pregnant women. Any new components of the vaccine formulation (adjuvants, excipients, stabilisers, preservatives, etc...) could also be tested for influences on development, although based on past experience the risks are limited by the very low dosages used. The conferred immunity following vaccination lasts for several years. Therefore, the developing conceptus may theoretically be exposed to the induced antibodies and/or sensitised T-cells, even if the pregnant woman was last vaccinated during childhood (particularly if she encounters the antigen during pregnancy through exposure to infection). However, it should be kept in mind that viral or bacterial infections represent a higher risk for a pregnant woman than the potential adverse effects related to vaccination or the associated immune response. Non-clinical safety studies may be employed as an aid for hazard identification. In these studies interactions of the vaccine with the maternal immune system or with the developmental systems of the offspring are considered. Post-natal examinations are necessary to detect all possible manifestations of developmental toxicity, such as effects on the immune system. Species selection for the preclinical studies is based on immunogenicity to the vaccine and the relative timing and rate of transfer of maternal antibodies to the offspring. A single study design is proposed for the pre- and post-natal developmental assessments of vaccines in
Hemming, Maria; Vesikari, Timo
Two live-attenuated oral vaccines (Rotarix™ and Rotateq®) against rotavirus gastroenteritis were licensed in 2006 and have been introduced into National Immunization Programs (NIPs) of several countries. Large scale use of rotavirus vaccines might cause antigenic pressure on circulating rotavirus types or lead to selection of new rotaviruses thus decreasing vaccine efficacy. We examined the nucleotide and amino acid sequences of the surface proteins VP7 and VP4 (cleaved to VP8(*) and VP5(*)) of a total of 108 G1P rotavirus strains collected over a 20-year period from 1992, including the years 2006-2009 when rotavirus vaccine (mainly Rotarix™) was available, and the years 2009-2012 after implementation of RotaTeq® vaccine into the NIP of Finland. In G1 VP7 no changes at amino acid level were observed. In VP8(*) periodical fluctuation of the sublineage over the study period was found with multiple changes both at nucleotide and amino acid levels. Most amino acid changes were in the dominant antigenic epitopes of VP8(*). A change in VP8(*) sublineage occurred between 2008 and 2009, with a temporal correlation to the use of Rotarix™ up to 30% coverage in the period. In contrast, no antigenic changes in the VP8(*) protein appeared to be correlated to the exclusive use of RotaTeq® vaccine after 2009. Nevertheless, long-term surveillance of antigenic changes in VP4 and also VP7 proteins in wild-type rotavirus strains is warranted in countries with large scale use of the currently licensed live oral rotavirus vaccines. Copyright © 2013 Elsevier B.V. All rights reserved.
Dennis J Faix
Full Text Available Population-based febrile respiratory illness surveillance conducted by the Department of Defense contributes to an estimate of vaccine effectiveness. Between January and March 2011, 64 cases of 2009 A/H1N1 (pH1N1, including one fatality, were confirmed in immunized recruits at Fort Jackson, South Carolina, suggesting insufficient efficacy for the pH1N1 component of the live attenuated influenza vaccine (LAIV.To test serologic protection, serum samples were collected at least 30 days post-vaccination from recruits at Fort Jackson (LAIV, Parris Island (LAIV and trivalent inactivated vaccine [TIV] at Cape May, New Jersey (TIV and responses measured against pre-vaccination sera. A subset of 78 LAIV and 64 TIV sera pairs from recruits who reported neither influenza vaccination in the prior year nor fever during training were tested by microneutralization (MN and hemagglutination inhibition (HI assays. MN results demonstrated that seroconversion in paired sera was greater in those who received TIV versus LAIV (74% and 37%. Additionally, the fold change associated with TIV vaccination was significantly different between circulating (2011 versus the vaccine strain (2009 of pH1N1 viruses (ANOVA p value = 0.0006. HI analyses revealed similar trends. Surface plasmon resonance (SPR analysis revealed that the quantity, IgG/IgM ratios, and affinity of anti-HA antibodies were significantly greater in TIV vaccinees. Finally, sequence analysis of the HA1 gene in concurrent circulating 2011 pH1N1 isolates from Fort Jackson exhibited modest amino acid divergence from the vaccine strain.Among military recruits in 2011, serum antibody response differed by vaccine type (LAIV vs. TIV and pH1N1 virus year (2009 vs. 2011. We hypothesize that antigen drift in circulating pH1N1 viruses contributed to reduce vaccine effectiveness at Fort Jackson. Our findings have wider implications regarding vaccine protection from circulating pH1N1 viruses in 2011-2012.
Educational aids include printed matter, aural media, visual media, audiovisual media and objects. A distinction is made between learning aids, which include blackboards, overhead projectors, flipcharts, wallcharts and pinboards, and learning aids, which include textbooks, worksheets, documentation and experimental equipment. The various aids are described and their use explained. The aids available at the School for Nuclear Technology of the Karlsruhe Nuclear Research Centre are described
Muzumdar, Jagannath M; Cline, Richard R
To provide an overview of supply and demand issues in the vaccine industry and the policy options that have been implemented to resolve these issues. Medline, Policy File, and International Pharmaceutical Abstracts were searched to locate academic journal articles. Other sources reviewed included texts on the topics of vaccine history and policy, government agency reports, and reports from independent think tanks. Keywords included vaccines, immunizations, supply, demand, and policy. Search criteria were limited to English language and human studies. Articles pertaining to vaccine demand, supply, and public policy were selected and reviewed for inclusion. By the authors. Vaccines are biologic medications, therefore making their development and production more difficult and costly compared with "small-molecule" drugs. Research and development costs for vaccines can exceed $800 million, and development may require 10 years or more. Strict manufacturing regulations and facility upgrades add to these costs. Policy options to increase and stabilize the supply of vaccines include those aimed at increasing supply, such as government subsidies for basic vaccine research, liability protection for manufacturers, and fast-track approval for new vaccines. Options to increase vaccine demand include advance purchase commitments, government stockpiles, and government financing for select populations. High development costs and multiple barriers to entry have led to a decline in the number of vaccine manufacturers. Although a number of vaccine policies have met with mixed success in increasing the supply of and demand for vaccines, a variety of concerns remain, including developing vaccines for complex pathogens and increasing immunization rates with available vaccines. New policy innovations such as advance market commitments and Medicare Part D vaccine coverage have been implemented and may aid in resolving some of the problems in the vaccine industry.
Data, Maps - SC Public Health Diseases and Conditions Flu Tuberculosis STD/HIV and Viral Hepatitis Zika Illnesses E. coli Listeriosis Salmonella Hepatitis A Shellfish Monitoring and Regulation Certified Shippers Vaccines Teen and Preteen Vaccines Vaccines Needed for School Admission Related Topics Perinatal Hepatitis
Mahapatra, Mana; Yuvaraj, S; Madhanmohan, M; Subramaniam, S; Pattnaik, B; Paton, D J; Srinivasan, V A; Parida, Satya
Foot-and-mouth disease (FMD) virus serotype O is the most common cause of FMD outbreaks in India and three of the six lineages that have been described are most frequently detected, namely Ind2001, PanAsia and PanAsia 2. We report the full capsid sequence of 21 serotype O viruses isolated from India between 2002 and 2012. All these viruses belong to the Middle East-South Asia (ME-SA) topotype. The serological cross-reactivity of a bovine post-vaccination serum pool raised against the current Indian vaccine strain, O/IND/R2/75,was tested by virus neutralisation test with the 23 Indian field isolates, revealing a good match between the vaccine and the field isolates. The cross reactivity of the O/IND/R2/75 vaccine with 19 field isolates from other countries (mainly from Asia and Africa) revealed a good match to 79% of the viruses indicating that the vaccine strain is broadly cross-reactive and could be used to control FMD in other countries. Comparison of the capsid sequences of the serologically non-matching isolates with the vaccine strain sequence identified substitutions in neutralising antigenic sites 1 and 2, which could explain the observed serological differences. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Duijzer, Evelot; Jaarsveld, Willem; Wallinga, Jacco; Dekker, Rommert
textabstractFor a large number of infectious diseases, vaccination is the most effective way to prevent an epidemic. However, the vaccine stockpile is hardly ever sufficient to treat the entire population, which brings about the challenge of vaccine allocation. To aid decision makers facing this challenge, we provide insights into the structure of this problem. We first investigate the dependence of health benefit on the fraction of people that receive vaccination, where we define health bene...
People working on the CERN site who wish to be vaccinated may go to the Infirmary (ground-floor, bldg. 57), with their vaccine, without a prior appointment. The vaccine can be reimbursed directly by Uniqa providing you attach the receipt and the prescription that you will receive from the Medical Service the day of your injection at the infirmary. Ideally, the vaccination should take place between 1st October and 30th November 2007 (preferably between 14:00 and 16:00). CERN staff aged 50 or over are recommended to have influenza vaccinations. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and those convalescing from serious medical problems or after serious surgical operations. The Medical Service will not administer vaccines for family members or retired staff members, who must contact their normal family doctor. Medical Service
Arndt, Channing; Jones, Edward Samuel; Tarp, Finn
of the main relationships; (ii) estimating the impact of aid on a range of final and intermediate outcomes; and (iii) quantifying a simplied representation of the full structural form, where aid impacts on growth through key intermediate outcomes. A coherent picture emerges: aid stimulates growth and reduces......Controversy over the aggregate impact of foreign aid has focused on reduced form estimates of the aid-growth link. The causal chain, through which aid affects developmental outcomes including growth, has received much less attention. We address this gap by: (i) specifying a structural model...... poverty through physical capital investment and improvements in health....
AIDS (acquired immune deficiency syndrome) is caused by HIV (human immunodeficiency virus), and is a syndrome that ... life-threatening illnesses. There is no cure for AIDS, but treatment with antiviral medicine can suppress symptoms. ...
Foreign aid has evolved significantly since the Second World War in response to a dramatically changing global political and economic context. This article (a) reviews this process and associated trends in the volume and distribution of foreign aid; (b) reviews the goals, principles and instituti......Foreign aid has evolved significantly since the Second World War in response to a dramatically changing global political and economic context. This article (a) reviews this process and associated trends in the volume and distribution of foreign aid; (b) reviews the goals, principles...... and institutions of the aid system; and (c) discusses whether aid has been effective. While much of the original optimism about the impact of foreign aid needed modification, there is solid evidence that aid has indeed helped further growth and poverty reduction...
Full Text Available Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver.
Ogholikhan, Sina; Schwarz, Kathleen B.
Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406
People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service
CERN Medical Service
People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor.CERN Medical Service
People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service
People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical service
Ruben, F L
Influenza is a modern day plague. In the young, the clinical picture is classical, but in the elderly, the disease may go unsuspected until complications such as pneumonia develop. Influenza A and B viruses are responsible, and these viruses mutate with great regularity. Antibodies to the HA and NA surface antigens of influenza viruses, both naturally and vaccine induced, are protective. The earliest influenza vaccines were crude, toxic, and ineffective. With modern purification techniques, the egg-grown viruses have been turned into safe, immunogenic, and effective killed-virus vaccines--whole virus and split virus. Surveillance permits the correct virus strains to be incorporated into each new vaccine. Those who have been experiencing the worst effects of influenza have been identified. These individuals need to be immunized each year. In the future, live influenza virus vaccines may offer the benefits of ease of administration and longer-lasting protection. Synthetic peptides, genetically engineered antigens, and even nonantigen (anti-idiotype) vaccines are possible, but such vaccines will require adjuvant enhancement. For the present, greater efforts must be made to use existing influenza vaccines.
Worldwide, at least 22 million people have been infected with HIV. The overwhelming majority of these cases, however, are in sub-Saharan Africa, Thailand, and India; approximately 15-20 million people are infected with the total number rapidly increasing. Approximately two million people are infected in the West, and the rate and extent of HIV infection are either plateauing or decreasing. In the West, HIV is contracted primarily through homosexual contact and IV drug use. HIV1-B is the prevalent strain of HIV in such settings. HIV in South Asia and sub-Saharan Africa, however, is mainly transmitted through heterosexual contact and consists of HIV-1 strains A, C, and E. There are therefore two distinct HIV epidemics taking place. Professor Max Essex of the Harvard AIDS Institute noted in his address at a conference on infectious diseases in New Delhi, India, that most planned vaccines and therapy for AIDS were developed in the West and thus targeted to combat HIV1-B. It seems likely, however, that other HIV subtypes will also take hold in the West and that an heterosexual epidemic of considerable magnitude should be anticipated. The high rate of HIV genetic mutation is of concern for both AIDS prevention and treatment. Essex further pointed out that the growing cost of treating AIDS patients with increasingly long lives has prompted a shift in the core of AIDS research from therapy to prevention. That levels of awareness about HIV/AIDS and the extent of sex education among youth are higher in more developed countries compared to in developing countries may play a role in the relatively lower incidence of new HIV cases in the West.
Full Text Available Antonio Miguel,1 Luis Sendra,1 Verónica Noé,2 Carles J Ciudad,2 Francisco Dasí,3,4 David Hervas,5 María José Herrero,1,6 Salvador F Aliño17 1Department of Pharmacology, Faculty of Medicine, University of Valencia, 2Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Barcelona, 3Research University Hospital of Valencia, INCLIVA Health Research Institute, 4Department of Physiology, Faculty of Medicine, University of Valencia Foundation, 5Biostatistics Unit, 6Pharmacogenetics Unit, Instituto de Investigación Sanitaria La Fe (IIS La Fe, 7Clinical Pharmacology Unit, ACM Hospital Universitario y Politécnico La Fe, Valencia, Spain Abstract: The antitumor response after therapeutic vaccination has a limited effect and seems to be related to the presence of T regulatory cells (Treg, which express the immunoregulatory molecules CTLA4 and Foxp3. The blockage of CTLA4 using antibodies has shown an effective antitumor response conducing to the approval of the human anti-CTLA4 antibody ipilimumab by the US Food and Drug Administration. On the other hand, Foxp3 is crucial for Treg development. For this reason, it is an attractive target for cancer treatment. This study aims to evaluate whether combining therapeutic vaccination with CTLA4 or Foxp3 gene silencing enhances the antitumor response. First, the “in vitro” cell entrance and gene silencing efficacy of two tools, 2'-O-methyl phosphorotioate-modified oligonucleotides (2'-OMe-PS-ASOs and polypurine reverse Hoogsteen hairpins (PPRHs, were evaluated in EL4 cells and cultured primary lymphocytes. Following B16 tumor transplant, C57BL6 mice were vaccinated with irradiated B16 tumor cells engineered to produce granulocyte-macrophage colony-stimulating factor (GM-CSF and were intraperitoneally treated with CTLA4 and Foxp3 2'-OMe-PS-ASO before and after vaccination. Tumor growth, mice survival, and CTLA4 and Foxp3 expression in blood cells were measured. The following
HIV/AIDS is high and that is why most patients cannot access HIV/AIDS treatment even though these drugs are supposed to .... Laboratory in New Mexico, Dr. Gerald Myers, and ... tuberculosis, and vaccinations against smallpox represented ...
Schalk, Johanna A C; Mooi, Frits R; Berbers, Guy A M; Aerts, Leon A G J M van; Ovelgönne, Hans; Kimman, Tjeerd G
DNA vaccines are based on the transfer of genetic material, encoding an antigen, to the cells of the vaccine recipient. Despite high expectations of DNA vaccines as a result of promising preclinical data their clinical utility remains unproven. However, much data is gathered in preclinical and
Bubeník, Jan; Šímová, Jana; Mikyšková, Romana; Vonka, V.
Roč. 27, č. 4 (2004), s. 161D ISSN 0147-958X. [International Congress of Immunology /12./ and Annual Conference of FOCIS /4./. Montreal, 18.07.2004-23.07.2004] Institutional research plan: CEZ:AV0Z5052915 Keywords : HPV 16 * tumour vaccines * dendritic cells Subject RIV: EC - Immunology Impact factor: 1.051, year: 2004
Holland, A.; Whittington, J.; Cohen, O.; Curfs, L.; Delahaye, F.; Dudley, O.; Horsthemke, B.; Lindgren, A. -C.; Nourissier, C.; Sharma, N.; Vogels, A.
Background: Prader-Willi Syndrome (PWS) is a rare genetically determined neurodevelopmental disorder with a complex phenotype that changes with age. The rarity of the syndrome and the need to control for different variables such as genetic sub-type, age and gender limits clinical studies of sufficient size in any one country. A clinical research…
diseases. Keywords. DNA vaccine, immune response, antibodies, infectious diseases. GENERAL .... tein vaccines require expensive virus/protein purification tech- niques as ... sphere continue to remain major health hazards in developing nations. ... significance since it can be produced at a very low cost and can be stored ...
Vaccination involves priming the immune system with an antigenic agent that mimics a virus or bacterium, which results in immunity against the “real” microorganism. Collective vaccination policies have played an important role in the control of infectious disease worldwide. They can serve the
Wagner, Ernst; Kircheis, Ralf; Crommelin, D.; Van Slooten, Maaike; Storm, Gert
The invention relates to a tumour vaccine with a tumour antigen base. In addition to a source of tumour antigens, the vaccine contains a release system for the delayed release of the active agent IFN- gamma , the active dose of IFN- gamma being 50 ng to 5 mu g. The IFN- gamma is released over a
Why get vaccinated?Rotavirus is a virus that causes diarrhea, mostly in babies and young children. The diarrhea can be severe, and lead ... and fever are also common in babies with rotavirus.Before rotavirus vaccine, rotavirus disease was a common ...
Konstantin A. Tsetsarkin
Full Text Available An arthropod-borne virus, Zika virus (ZIKV, has recently emerged as a major human pathogen. Associated with complications during perinatal development and Guillain-Barré syndrome in adults, ZIKV raises new challenges for understanding the molecular determinants of flavivirus pathogenesis. This underscores the necessity for the development of a reverse genetic system based on an epidemic ZIKV strain. Here, we describe the generation and characterization in cell cultures of an infectious cDNA clone of ZIKV isolated from the 2015 epidemic in Brazil. The cDNA-derived ZIKV replicated efficiently in a variety of cell lines, including those of both neuronal and placental origin. We observed that the growth of cDNA-derived virus was attenuated compared to the growth of the parental isolate in most cell lines, which correlates with substantial differences in sequence heterogeneity between these viruses that were determined by deep-sequencing analysis. Our findings support the role of genetic diversity in maintaining the replicative fitness of viral populations under changing conditions. Moreover, these results indicate that caution should be exercised when interpreting the results of reverse-genetics experiments in attempts to accurately predict the biology of natural viruses. Finally, a Vero cell-adapted cDNA clone of ZIKV was generated that can be used as a convenient platform for studies aimed at the development of ZIKV vaccines and therapeutics.
Esmaeilzadeh, Abdolreza; Farshbaf, Alieh; Erfanmanesh, Maryam
HIV and AIDS is one of the biggest challenges all over the world. There are an approximately 34 million people living with the virus, and a large number of them become infected each year. Although there are some antiviral drugs for HIV viral load reduction, they are not sufficient. There is no cure for AIDS. Nowadays natural resistance or immunity has absorbed attentions. Because in some HIV positive patients progression trend is slow or even they indicate resistance to AIDS. One of the most interesting approaches in this category is CCR5 gene. CCR5 is a main cc-chemokine co-receptor that facilitates HIV-1 entry to macrophage and CD4(+) T cells. To now, many polymorphisms have been known by CCR5 gene that produces a truncated protein with no function. So, HIV-1 could not entry to immune-cells and the body resistant to HIV/AIDS. Δ32/Δ32 and m303/m303 homozygotes are example of mutations that could create this resistance mechanism. There is a new treatment, such as Hematopoietic Stem Cell transplantation (HSCT) in Berlin and Boston patients for Δ32/Δ32 mutation. It could eliminate co-receptor antagonist and highly-active-anti retroviral therapy (HAART) drugs problems such as toxicity, low safety and side-effects. Now there, the aim of this hypothesis will be evaluation of a new mutation CCR5 m303/m303 as autologous HSCT. This novel hypothesis indicates that autologous HSCT for m303/m303 could be effective treatment for anyone HIV/AIDS affected patient worldwide. Copyright © 2015 Elsevier Ltd. All rights reserved.
Edlefsen, Paul T; Gilbert, Peter B; Rolland, Morgane
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.
Richey, Lisa Ann; Ponte, Stefano
A critical account of the rise of celebrity-driven “compassionate consumption” Cofounded by the rock star Bono in 2006, Product RED exemplifies a new trend in celebrity-driven international aid and development, one explicitly linked to commerce, not philanthropy. Brand Aid offers a deeply informed...
Foreign aid has evolved significantly since the Second World War in response to a dramatically changing global political and economic context. This article (a) reviews this process and associated trends in the volume and distribution of foreign aid; (b) reviews the goals, principles...
Rodrigues, Charlene M C; Pinto, Marta V; Sadarangani, Manish; Plotkin, Stanley A
Currently used vaccines have had major effects on eliminating common infections, largely by duplicating the immune responses induced by natural infections. Now vaccinology faces more complex problems, such as waning antibody, immunosenescence, evasion of immunity by the pathogen, deviation of immunity by the microbiome, induction of inhibitory responses, and complexity of the antigens required for protection. Fortunately, vaccine development is now incorporating knowledge from immunology, structural biology, systems biology and synthetic chemistry to meet these challenges. In addition, international organisations are developing new funding and licensing pathways for vaccines aimed at pathogens with epidemic potential that emerge from tropical areas. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Full Text Available BACKGROUND: The aim of this study was to analyse the genetic patterns of Hemagglutinin (HA genes of influenza A strains circulating on Corsica Island during the 2006-2009 epidemic seasons and the 2009-2010 pandemic season. METHODS: Nasopharyngeal samples from 371 patients with influenza-like illness (ILI were collected by General Practitioners (GPs of the Sentinelles Network through a randomised selection routine. RESULTS: Phylogenetic analysis of HA revealed that A/H3N2 strains circulating on Corsica were closely related to the WHO recommended vaccine strains in each analyzed season (2006-2007 to 2008-2009. Seasonal Corsican influenza A/H1N1 isolated during the 2007-2008 season had drifted towards the A/Brisbane/59/2007 lineage, the A/H1N1 vaccine strain for the 2008-2009 season. The A/H1N1 2009 (A/H1N1pdm strains isolated on Corsica Island were characterized by the S220T mutation specific to clade 7 isolates. It should be noted that Corsican isolates formed a separate sub-clade of clade 7 as a consequence of the presence of the fixed substitution D222E. The percentages of the perfect match vaccine efficacy, estimated by using the p(epitope model, against influenza viruses circulating on Corsica Island varied substantially across the four seasons analyzed, and tend to be highest for A/H1N1 compared with A/H3N2 vaccines, suggesting that cross-immunity seems to be stronger for the H1 HA gene. CONCLUSION: The molecular analysis of the HA gene of influenza viruses that circulated on Corsica Island between 2006-2010 showed for each season the presence of a dominant lineage characterized by at least one fixed mutation. The A/H3N2 and A/H1N1pdm isolates were characterized by multiples fixation at antigenic sites. The fixation of specific mutations at each outbreak could be explained by the combination of a neutral phenomenon and a founder effect, favoring the presence of a dominant lineage in a closed environment such as Corsica Island.
Full Text Available When HIV was discovered and established as the cause of AIDS in 1983–1984, many people believed that a vaccine would be rapidly developed. However, 30 years have passed and we are still struggling to develop an elusive vaccine. In trying to achieve that goal, different scientific paradigms have been explored. Although major progress has been made in understanding the scientific basis for HIV vaccine development, efficacy trials have been critical in moving the field forward. Major lessons learned are: the development of an HIV vaccine is an extremely difficult challenge; the temptation of just following the fashion should be avoided; clinical trials are critical, especially large-scale efficacy trials; HIV vaccine research will require long-term commitment; and sustainable collaborations are needed to accelerate the development of an HIV vaccine. Concrete actions must be implemented with the sense of urgency imposed by the severity of the AIDS epidemic.
Østerhus, Sven Frederick
The Cochrane Library was systematically searched for meta-analyses regarding influenza vaccination of various populations, both healthy and sick. An effect in reducing the number of cases of influenza, influenza-like illness or complications to influenza was found in some studies, but, generally......, the quality of the studies was low, and several studies lacked hard clinical endpoints. Data on adverse effects were scarce. More randomised controlled trials investigating the effects of influenza vaccination are warranted....
... Influenza Types Seasonal Avian Swine Variant Pandemic Other Flu Vaccine Safety Information Questions & Answers Language: English (US) ... safety of flu vaccines monitored? Egg Allergy Are flu vaccines safe? Flu vaccines have good safety record. ...
... Seasonal Avian Swine Variant Pandemic Other Thimerosal in Flu Vaccine Questions & Answers Language: English (US) Español Recommend ... and/or fungi from contaminating the vaccine. Do flu vaccines contain thimerosal? Flu vaccines in multi-dose ...
... an ENT Doctor Near You Ear Infection and Vaccines Ear Infection and Vaccines Patient Health Information News ... or may need reinsertion over time. What about vaccines? A vaccine is a preparation administered to stimulate ...
Gian Vincenzo Zuccotti
Full Text Available Streptococcus pneumoniae (SP is a gram-positive bacterium with more than 90 known serotypes causing around 11% of all deaths worldwide in children aged 1-59 months. A new era in prevention of SP-related diseases started in at the beginning of 2000s when a 7-valent pneumococcal conjugate vaccine (PCV7 was recommended as the vaccine of choice in pediatric age. PCV7 dramatically reduced invasive pneumococcal diseases (IPD among children with indirect effects noted among other age groups as well. However, thanks to a strict surveillance network, an increase in non-vaccine serotypes (NVTs causing IPD was noted worldwide and in late 2000s a new second generation vaccine (13-valent pneumococcal conjugate vaccine-PCV13 with an expanded serotype coverage was licensed. Due to the lack of solid effectiveness data, up to know it is difficult to predict how the composition of NVTs will change after the large-scale introduction of PCV13 or whether the characteristics of the serotypes will change. Long-term surveillance of both IPD, pneumonia, acute otitis media and carriage will be crucial to ascertain whether these second generation vaccines are having the desired effect of reducing the incidence of diseases in the long term. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research
Fink, R.K.; Callow, R.A.; Larson, T.K.; Ransom, V.H.
An expert system called the ATHENA AIDE that assists in the preparation of input models for the ATHENA thermal-hydraulics code has been developed by researchers at the Idaho National Engineering Laboratory. The ATHENA AIDE uses a menu driven graphics interface and rule-based and object-oriented programming techniques to assist users of the ATHENA code in performing the tasks involved in preparing the card image input files required to run ATHENA calculations. The ATENA AIDE was developed and currently runs on single-user Xerox artificial intelligence workstations. Experience has shown that the intelligent modeling environment provided by the ATHENA AIDE expert system helps ease the modeling task by relieving the analyst of many mundane, repetitive, and error prone procedures involved in the construction of an input model. This reduces errors in the resulting models, helps promote standardized modeling practices, and allows models to be constructed more quickly than was previously possible
... Relations Cyber Infrastructure Computational Biology Equal Employment Opportunity Ethics Global Research Office of Mission Integration and Financial Management Strategic Planning Workforce Effectiveness Workplace Solutions Technology Transfer Intellectual Property Division of AIDS ...
Shulman, Lester M; Martin, Javier; Sofer, Danit; Burns, Cara C; Manor, Yossi; Hindiyeh, Musa; Gavrilin, Eugene; Wilton, Thomas; Moran-Gilad, Jacob; Gamzo, Ronni; Mendelson, Ella; Grotto, Itamar
Israel has >95% polio vaccine coverage with the last 9 birth cohorts immunized exclusively with inactivated polio vaccine (IPV). Using acute flaccid paralysis and routine, monthly countrywide environmental surveillance, no wild poliovirus circulation was detected between 1989 and February 2013, after which wild type 1 polioviruses South Asia genotype (WPV1-SOAS) have persistently circulated in southern Israel and intermittently in other areas without any paralytic cases as determined by intensified surveillance of environmental and human samples. We aimed to characterize antigenic and neurovirulence properties of WPV1-SOAS silently circulating in a highly vaccinated population. WPV1-SOAS capsid genes from environmental and stool surveillance isolates were sequenced, their neurovirulence was determined using transgenic mouse expressing the human poliovirus receptor (Tg21-PVR) mice, and their antigenicity was characterized by in vitro neutralization using human sera, epitope-specific monoclonal murine anti-oral poliovirus vaccine (OPV) antibodies, and sera from IPV-immunized rats and mice. WPV1 amino acid sequences in neutralizing epitopes varied from Sabin 1 and Mahoney, with little variation among WPV1 isolates. Neutralization by monoclonal antibodies against 3 of 4 OPV epitopes was lost. Three-fold lower geometric mean titers (Z = -4.018; P < .001, Wilcoxon signed-rank test) against WPV1 than against Mahoney in human serum correlated with 4- to 6-fold lower neutralization titers in serum from IPV-immunized rats and mice. WPV1-SOAS isolates were neurovirulent (50% intramuscular paralytic dose in Tg21-PVR mice: log10(7.0)). IPV-immunized mice were protected against WPV1-induced paralysis. Phenotypic and antigenic profile changes of WPV1-SOAS may have contributed to the intense silent transmission, whereas the reduced neurovirulence may have contributed to the absence of paralytic cases in the background of high population immunity. © The Author 2014. Published by
Basra, Gurjot; Jajoria, Praveen; Gonzalez, Emilio
Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease. Multiple scientific articles have documented that vaccinations for influenza, MMR, and HBV, to name a few, could be triggers of RA in genetically predisposed individuals. However, there is limited data regarding the association of swine flu vaccine (H1N1) and RA. We report the case of a Mexican American female who developed RA right after vaccination with H1N1 vaccine. Genetically, RA has consistently been associated with an epitope in the third hypervariable region of the HLA-DR β chains, known as the "shared epitope", which is found primarily in DR4 and DR1 regions. The presence of HLA-DRB1 alleles is associated with susceptibility to RA in Mexican Americans. Hence, certain individuals with the presence of the "shared epitope" may develop RA following specific vaccinations. To our knowledge, this is the first reported case of RA following vaccination with the swine flu vaccine.
The Sun article, "Employers finding that AIDS in the workplace is a managerial nightmare" (April 3), did not accurately portray the status of AIDS in the workplace. The AIDS virus, HTLV III, is transmitted by body fluids, primarily semen and blood, and there is no known risk of transmitting the virus by casual contact in the workplace. The Center for Disease Control (CDC) released guidelines for child care workers last August. Guidelines on preventing transmission of AIDS in the workplace were issued by CDC in November 1985. These guidelines specifically discussed health care, personal service, and food service workers. The recommendations were against routine screening. Furthermore, employment should not be restricted on the basis of a positive HTLV III antibody test. A person with HTLV III infection should be exempt from the workplace only if there are circumstances interfering with job performance. In Maryland, the Governor's Task Force on AIDS has gone on record as endorsing CDC guidelines related to employment. Furthermore, the task force condemns discrimination based on the disease AIDS, AIDS Related Complex (ARC), or HTLV III infection. Increasingly AIDS patients are being considered legally disabled and therefore are protected by federal and state laws prohibiting discrimination on the basis of a handicap. Marylanders who are subjected to mandatory HTLV III screening in the workplace, or if discriminated against on the basis of HTLV III inefction, should contact the Maryland Commission on Human Relations, the Maryland Department of Health and Mental Hygiene, or the Health Education Resource Organization (HERO). All 3 of these resources guarantee confidentiality. It is only by employees reporting incidents that a nightmare in the workplace can be avoided in Maryland. full text
Poirot, P; Martin, J F
When Jonas Salk announced in the mid-50s the availability of a new vaccine against poliomyelitis, the world had the impression that it was now controlling infectious diseases. In fact, the success of this vaccine has been considerable and although some innovations lead to the launch of vaccines against flu, measles, rubella or mumps, the world vaccine market remained remarkably stable till the mid-80s. However, since 1984 (launch of the hepatitis B vaccine) there have been very substantial changes and further change is expected in the next ten years in the world market. Today, big companies are making a concentrated supply: Pasteur Mérieux with its subsidiary Connaught, SmithKline Beecham who acquired the Belgian company RIT, and Merck & Co. who is joining its forces with Pasteur Mérieux. Medium sized and small companies remain and reflect the situation of the past, but must work hard to secure their long term existence eventhough the world demand is going to double before the year 2000. Very substantial technological innovations explain to a large extent the development of the supply: progress in molecular biology, and particularly genetic engineering, lead to recombinant vaccines of which hepatitis B is the best example with worldwide sales in the range of $600 million a year. Similarly, conjugation technologies have allowed the development of new vaccines against meningitis, particularly Haemophilus influenzae type b. More recently, an efficacious vaccine against hepatitis A has been launched and many new products will be marketed in the next years against herpes, Lyme disease, and agents of other meningitis, etc.(ABSTRACT TRUNCATED AT 250 WORDS)
Full Text Available Staphylococcus aureus is a leading cause of bovine intramammary infections (IMIs that can evolve into difficult-to-treat chronic mastitis. To date, no vaccine formulation has shown high protective efficacy against S. aureus IMI, partly because this bacterium can efficiently evade the immune system. For instance, S. aureus small colony variants (SCVs have intracellular abilities and can persist without producing invasive infections. As a first step towards the development of a live vaccine, this study describes the elaboration of a novel attenuated mutant of S. aureus taking advantage of the SCV phenotype. A genetically stable SCV was created through the deletion of the hemB gene, impairing its ability to adapt and revert to the invasive phenotype. Further attenuation was obtained through inactivation of gene vraG (SACOL0720 which we previously showed to be important for full virulence during bovine IMIs. After infection of bovine mammary epithelial cells (MAC-T, the double mutant (ΔvraGΔhemB was less internalized and caused less cell destruction than that seen with ΔhemB and ΔvraG, respectively. In a murine IMI model, the ΔvraGΔhemB mutant was strongly attenuated, with a reduction of viable counts of up to 5-log10 CFU/g of mammary gland when compared to the parental strain. A complete clearance of ΔvraGΔhemB from glands was observed whereas mortality rapidly (48h occurred with the wild-type strain. Immunization of mice using subcutaneous injections of live ΔvraGΔhemB raised a strong immune response as judged by the high total IgG titers measured against bacterial cell extracts and by the high IgG2a/IgG1 ratio observed against the IsdH protein. Also, ΔvraGΔhemB had sufficient common features with bovine mastitis strains so that the antibody response also strongly recognized strains from a variety of mastitis associated spa types. This double mutant could serve as a live-attenuated component in vaccines to improve cell-mediated immune
Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca
The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.
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.
Li, Lei; Saade, Fadi; Petrovsky, Nikolai
DNA vaccines have evolved greatly over the last 20 years since their invention, but have yet to become a competitive alternative to conventional protein or carbohydrate based human vaccines. Whilst safety concerns were an initial barrier, the Achilles heel of DNA vaccines remains their poor immunogenicity when compared to protein vaccines. A wide variety of strategies have been developed to optimize DNA vaccine immunogenicity, including codon optimization, genetic adjuvants, electroporation and sophisticated prime-boost regimens, with each of these methods having its advantages and limitations. Whilst each of these methods has contributed to incremental improvements in DNA vaccine efficacy, more is still needed if human DNA vaccines are to succeed commercially. This review foresees a final breakthrough in human DNA vaccines will come from application of the latest cutting-edge technologies, including "epigenetics" and "omics" approaches, alongside traditional techniques to improve immunogenicity such as adjuvants and electroporation, thereby overcoming the current limitations of DNA vaccines in humans. Copyright © 2012 Elsevier B.V. All rights reserved.
Trebbien, Ramona; Fischer, Thea K; Krause, Tyra Grove
BACKGROUND: In Denmark, influenza A virus of the subtype H3N2 has been dominating the 2016/17 season, as in most countries of the Northern Hemisphere. OBJECTIVES: This study was conducted as part of the Danish seasonal influenza surveillance programme to genetically characterize circulating H3N2...
Krummenacher, P.; Renaud, B.; Marechal, F.; Favrat, D.
This report presents a new methodological approach for the optimal design of energy-integrated batch processes. The main emphasis is put on indirect and, to some extend, on direct heat exchange networks with the possibility of introducing closed or open storage systems. The study demonstrates the feasibility of optimising with genetic algorithms while highlighting the pros and cons of this type of approach. The study shows that the resolution of such problems should preferably be done in several steps to better target the expected solutions. Demonstration is made that in spite of relatively large computer times (on PCs) the use of genetic algorithm allows the consideration of both continuous decision variables (size, operational rating of equipment, etc.) and integer variables (related to the structure at design and during operation). Comparison of two optimisation strategies is shown with a preference for a two-steps optimisation scheme. One of the strengths of genetic algorithms is the capacity to accommodate heuristic rules, which can be introduced in the model. However, a rigorous modelling strategy is advocated to improve robustness and adequate coding of the decision variables. The practical aspects of the research work are converted into a software developed with MATLAB to solve the energy integration of batch processes with a reasonable number of closed or open stores. This software includes the model of superstructures, including the heat exchangers and the storage alternatives, as well as the link to the Struggle algorithm developed at MIT via a dedicated new interface. The package also includes a user-friendly pre-processing using EXCEL, which is to facilitate to application to other similar industrial problems. These software developments have been validated both on an academic and on an industrial type of problems. (author)
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 ...
Les chèvres seront vaccinées à l'aide du nouveau vaccin recombinant vivant ou inactivé, puis infectées de façon expérimentale par la bactérie Mccp afin de déterminer si le vaccin offre une protection. Ce projet utilisera des outils de biologie synthétique de pointe pour mettre au point un vaccin contre la PPCC qui se ...
Griebel, Philip J
The control and prevention of bovine viral diarrhea virus (BVDV) infections has provided substantial challenges. Viral genetic variation, persistent infections, and viral tropism for immune cells have complicated disease control strategies. Vaccination has, however, provided an effective tool to prevent acute systemic infections and increase reproductive efficiency through fetal protection. There has been substantial controversy about the safety and efficacy of BVDV vaccines, especially when comparing killed versus modified-live viral (MLV) vaccines. Furthermore, numerous vaccination protocols have been proposed to protect the fetus and ensure maternal antibody transfer to the calf. These issues have been further complicated by reports of immune suppression during natural infections and following vaccination. While killed BVDV vaccines provide the greatest safety, their limited immunogenicity makes multiple vaccinations necessary. In contrast, MLV BVDV vaccines induce a broader range of immune responses with a longer duration of immunity, but require strategic vaccination to minimize potential risks. Vaccination strategies for breeding females and young calves, in the face of maternal antibody, are discussed. With intranasal vaccination of young calves it is possible to avoid maternal antibody interference and induce immune memory that persists for 6-8 months. Thus, with an integrated vaccination protocol for both breeding cows and calves it is possible to maximize disease protection while minimizing vaccine risks.
Full Text Available ABSTRAKPenyakit demam Dengue endemik di lebih dari 100 negara di dunia. Obat anti virus Dengue efektif belum ditemukan danpengendalian vektor dinilai kurang efektif, sehingga diperlukan upaya pencegahan dengan vaksinasi. Vaksin Dengue yangideal adalah murah, mencakup 4 serotipe, efektif dalam memberikan kekebalan, cukup diberikan sekali seumur hidup, aman,memberi kekebalan jangka panjang, stabil dalam penyimpanan dan stabil secara genetis (tidak bermutasi. Beberapakandidat vaksin yang telah dan sedang dikembangkan oleh para peneliti di seluruh dunia adalah tetravalent live attenuatedvaccine, vaksin Chimera (ChimeriVax, vaksin subunit dan vaksin DNA. Vaksin Dengue dipandang sebagai pendekatan yangefektif dan berkesinambungan dalam mengendalikan penyakit Dengue. Tahun 2003 telah terbentuk Pediatric DengueVaccine Initiative (PDVI, yaitu sebuah konsorsium internasional yang bergerak dalam advokasi untuk meyakinkanmasyarakat internasional akan penting dan mendesaknya vaksin Dengue. Konsorsium vaksin Dengue Indonesia saat iniberupaya mengembangkan vaksin Dengue dengan menggunakan strain virus lokal.Kata kunci: Dengue, virus, vaksinABSTRACTDengue fever is endemic in more than 100 countries in the world. The effective dengue antiviral drug has not been found yet,and vector control is considered less effective. Prevention program by vaccination is needed. An ideal dengue vaccine shouldbe inexpensive, covering four serotypes (tetravalent, effective in providing immunity, given once a lifetime, safe, stable instorage and genetically. Several vaccine candidates have been and are being developed included attenuated tetravalentvaccine, ChimeriVax, sub- unit vaccines and DNA vaccines. Dengue vaccine is seen as an effective and sustainable approachto controll Dengue infection. In 2003, Pediatric Dengue Vaccine Initiative (PDVI has been formed as an internationalconsortium involved in advocacy to convince the international community about the essence and urgency
Whitfield, Lindsay; Fraser, Alastair
This article presents a new analytical approach to the study of aid negotiations. Building on existing approaches but trying to overcome their limitations, it argues that factors outside of individual negotiations (or the `game' in game-theoretic approaches) significantly affect the preferences...
Halsey, Neal A; Talaat, Kawsar R; Greenbaum, Adena; Mensah, Eric; Dudley, Matthew Z; Proveaux, Tina; Salmon, Daniel A
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.
Bärnighausen, Till; Bloom, David E; Cafiero-Fonseca, Elizabeth T; O'Brien, Jennifer Carroll
Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery.
Avrett, Sam; Collins, Chris
Volume seven of the Review will mark the tenth anniversary of the Canadian HIV/AIDS Legal Network with a series of articles that describe past developments and future directions in several areas of policy and law related to HIV/AIDS. The following article is the first of these, discussing current challenges and future directions in the development of and access to HIV vaccines. It argues that governments are under public health, ethical, and legal obligations to develop and provide access to HIV vaccines. It further explains what is required for governments to fulfill their obligations: additional commitment and resources for HIV vaccine development in the context of increased global research and development regarding diseases of the poor; increased support and advocacy for partnerships to develop HIV vaccines; enhanced regulatory capacity in every country to review, approve, and monitor HIV vaccines; and assurance of global supply of, procurement of, delivery of, and access to vaccines in the context of efforts to increase global access to public health measures and technologies.
Licensed live vaccines (polio, MMR) - Radiation- attenuated sporozoites - Genetically- attenuated sporozoites 2011 MHS Conference Whole Organism...Not sufficiently attenuated Seattle Biomedical , Gates Foundation, WEHI and USMMVP 2011 MHS Conference Subunit approach- RTS,S Vaccine RTS,S is...Ad Boost DNA plasmids [Prime] – Encoding malaria proteins CSP and AMA1 Adenovirus 5 ( attenuated )[Boost] – Encoding malaria proteins CSP and AMA1
Bissa, Massimiliano; Illiano, Elena; Pacchioni, Sole; Paolini, Francesca; Zanotto, Carlo; De Giuli Morghen, Carlo; Massa, Silvia; Franconi, Rosella; Radaelli, Antonia; Venuti, Aldo
Considering the high number of new cases of cervical cancer each year that are caused by human papilloma viruses (HPVs), the development of an effective vaccine for prevention and therapy of HPV-associated cancers, and in particular against the high-risk HPV-16 genotype, remains a priority. Vaccines expressing the E6 and E7 proteins that are detectable in all HPV-positive pre-cancerous and cancer cells might support the treatment of HPV-related lesions and clear already established tumors. In this study, DNA and fowlpox virus recombinants expressing the E6F47R mutant of the HPV-16 E6 oncoprotein were generated, and their correct expression verified by RT-PCR, Western blotting and immunofluorescence. Immunization protocols were tested in a preventive or therapeutic pre-clinical mouse model of HPV-16 tumorigenicity using heterologous (DNA/FP) or homologous (DNA/DNA and FP/FP) prime/boost regimens. The immune responses and therapeutic efficacy were evaluated by ELISA, ELISPOT assays, and challenge with TC-1* cells. In the preventive protocol, while an anti-E6-specific humoral response was just detectable, a specific CD8(+) cytotoxic T-cell response was elicited in immunized mice. After the challenge, there was a delay in cancer appearance and a significant reduction of tumor volume in the two groups of E6-immunized mice, thus confirming the pivotal role of the CD8(+) T-cell response in the control of tumor growth in the absence of E6-specific antibodies. In the therapeutic protocol, in-vivo experiments resulted in a higher number of tumor-free mice after the homologous DNA/DNA or heterologous DNA/FP immunization. These data establish a preliminary indication for the prevention and treatment of HPV-related tumors by the use of DNA and avipox constructs as safe and effective immunogens following a prime/boost strategy. The combined use of recombinants expressing both E6 and E7 proteins might improve the antitumor efficacy, and should represent an important approach to
Full Text Available The route and method of immunization, as well as the cellular localization of the antigen, can influence the generation of an immune response. In general, intramuscular immunization results in Th1 responses, whereas intradermal delivery of DNA by gene gun immunization often results in more Th2 responses. Here we investigate how altering the cellular localization of the tumor antigen CEA (carcinoembryonic antigen affects the quality and amplitude of DNA vaccine-induced antibody responses in mice following intradermal delivery of DNA by a needle-free jet injection device (Biojector. CEA was expressed either in a membrane-bound form (wild-type CEA or in two truncated forms (CEA6 and CEA66 with cytoplasmic localization, where CEA66 was fused to a promiscuous T-helper epitope from tetanus toxin. Repeated intradermal immunization of BALB/c mice with DNA encoding wild-type CEA produced high antibody titers of a mixed IgG1/IgG2a ratio. In contrast, utilizing the DNA construct that resulted in intracellular targeting of CEA led to a reduced capacity to induce CEA-specific antibodies, but instead induced a Th1-biased immune response.
Rella, Antonella; Mor, Visesato; Farnoud, Amir M; Singh, Ashutosh; Shamseddine, Achraf A; Ivanova, Elitza; Carpino, Nicholas; Montagna, Maria T; Luberto, Chiara; Del Poeta, Maurizio
Cryptococcosis caused by Cryptococcus neoformans and Cryptococcus gattii affects a large population and is a cause of significant morbidity and mortality. Despite its public health burden, there are currently no vaccines against cryptococcosis and new strategies against such infections are needed. In this study, we demonstrate that C. neoformans has the biochemical ability to metabolize sterylglucosides (SGs), a class of immunomodulatory glycolipids. Genetic manipulations that eliminate cryptococccal sterylglucosidase lead to the accumulation of SGs and generate a mutant strain (Δsgl1) that is non-pathogenic in the mouse models of cryptococcosis. Interestingly, this mutant strain acts as a vaccine strain and protects mice against cryptococcosis following infection with C. neoformans or C. gattii. The immunity induced by the Δsgl1 strain is not CD4(+) T-cells dependent. Immunocompromised mice, which lack CD4(+) T-cells, are able to control the infection by Δsgl1 and acquire immunity against the challenge by wild-type C. neoformans following vaccination with the Δsgl1 strain. These findings are particularly important in the context of HIV/AIDS immune deficiency and suggest that the Δsgl1 strain might provide a potential vaccination strategy against cryptococcosis.
Alberer, Martin; Löscher, Thomas
The prevention of infectious diseases by vaccination and by counselling about malaria prophylaxis is a central aspect of travel medicine. Besides mandatory vaccinations required for entry to certain countries various vaccinations may be indicated depending on destination and type of travel as well as on individual risks of the traveler. In addition, pre-travel counselling should always include a check-up of standard vaccinations. Protection against mosquito bites is the basis of malaria prophylaxis. The addition of chemoprophylaxis is warranted in high risk areas. When regular chemoprophylaxis is not applied it is recommended to carry an appropriate antimalarial drug which can be used for emergency stand-by treatment in case of unexplained fever and when medical attention is not available within 24 hours. Travelers should realize that self-treatment is a first-aid measure and that they should still seek medical advice as soon as possible. © Georg Thieme Verlag KG Stuttgart · New York.
Full Text Available Tactile aids, which translate sound waves into vibrations that can be felt by the skin, have been used for decades by people with severe/profound hearing loss to enhance speech/language development and improve speechreading.The development of tactile aids dates from the efforts of Goults and his co-workers in the 1920s; Although The power supply was too voluminous and it was difficult to carry specially by children, it was too huge and heavy to be carried outside the laboratories and its application was restricted to the experimental usage. Nowadays great advances have been performed in producing this instrument and its numerous models is available in markets around the world.
Mužíková, Gabriela; Laga, Richard
Roč. 65, Suppl. 2 (2016), S203-S216 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LQ1604 Institutional support: RVO:61389013 Keywords : vaccine delivery * cellular and humoral immunity * polymer immunostimulants Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.461, year: 2016 http://www.biomed.cas.cz/physiolres/pdf/65%20Suppl%202/65_S203.pdf
... During Pregnancy Frequently Asked Questions about Vaccine Recalls Historical Vaccine Safety Concerns FAQs about GBS and Menactra ... CISA Resources for Healthcare Professionals Evaluation Current Studies Historical Background 2001-12 Publications Technical Reports Vaccine Safety ...
... for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More sharing ... in the primary immunization series in infants Report Adverse Event Report a Vaccine Adverse Event Contact FDA ( ...
Chettri, Jiwan Kumar
vaccines have reduced the need for usage of antibiotics with more than 99 % since the 1980s. Fish can be vaccinated by three different administration routes: injection, immersion and oral vaccination. Injection vaccination (intraperitoneal injection of vaccine) is the most time consuming and labor...... intensive method, which however, provides the best protection of the fish. Immersion vaccination is used for immunization of a high number of small fish is cost-efficient and fast (30 sec immersion into vaccine). Oral vaccination (vaccine in feed) is the least efficient. As in higher vertebrates fish...... respond to vaccination by increasing the specific antibody titer and by activating the cellular responses. My talk will cover vaccination methods in fish, immune responses and some adverse effect of oil-adjuvanted vaccines in fish with reference to our work in rainbow trout, Oncorhynchus mykiss....
Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at http://www.cdc.gov/hpv. HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...
Ampofo, William K; Baylor, Norman; Cobey, Sarah; Cox, Nancy J; Daves, Sharon; Edwards, Steven; Ferguson, Neil; Grohmann, Gary; Hay, Alan; Katz, Jacqueline; Kullabutr, Kornnika; Lambert, Linda; Levandowski, Roland; Mishra, A C; Monto, Arnold; Siqueira, Marilda; Tashiro, Masato; Waddell, Anthony L; Wairagkar, Niteen; Wood, John; Zambon, Maria; Zhang, Wenqing
for measuring immunity. • Standardized seroepidemiological surveys to assess the impact of influenza in a population could help to establish well-characterized banks of age-stratified representative sera as a national, regional and global resource, while providing direct evidence of the specific benefits of vaccination. • Advances in high-throughput genetic sequencing coupled with advanced bioinformatics tools, together with more X-ray crystallographic data, should accelerate understanding of the genetic and phenotypic changes that underlie virus evolution and more specifically help to predict the influence of amino acid changes on virus antigenicity. • Complex mathematical modelling techniques are increasingly being used to gain insights into the evolution and epidemiology of influenza viruses. However, their value in predicting the timing and nature of future antigenic and genetic changes is likely to be limited at present. The application of simpler non-mechanistic statistical algorithms, such as those already used as the basis of antigenic cartography, and phylogenetic modelling are more likely to be useful in facilitating vaccine virus selection and in aiding assessment of the pandemic potential of avian and other animal influenza viruses. • The adoption of alternative vaccine technologies - such as live-attenuated, quadrivalent or non-HA-based vaccines - has significant implications for vaccine virus selection, as well as for vaccine regulatory and manufacturing processes. Recent collaboration between the GISRS and vaccine manufacturers has resulted in the increased availability of egg isolates and high-growth reassortants for vaccine production, the development of qualified cell cultures and the investigation of alternative methods of vaccine potency testing. WHO will continue to support these and other efforts to increase the reliability and timeliness of the global influenza vaccine supply. • The WHO GISRS and its partners are continually working to
Dalton, K P; Nicieza, I; de Llano, D; Gullón, J; Inza, M; Petralanda, M; Arroita, Z; Parra, F
Despite the success of vaccination against myxoma virus, myxomatosis remains a problem on rabbit farms throughout Spain and Europe. In this study we set out to evaluate possible causes of myxoma virus (MYXV) vaccine failures addressing key issues with regard to pathogen, vaccine and vaccination strategies. This was done by genetically characterising MYXV field isolates from farm outbreaks, selecting a representative strain for which to assay its virulence and measuring the protective capability of a commercial vaccine against this strain. Finally, we compare methods (route) of vaccine administration under farm conditions and evaluate immune response in vaccinated rabbits. The data presented here show that the vaccine tested is capable of eliciting protection in rabbits that show high levels of seroconversion. However, the number of animals failing to seroconvert following subcutaneous vaccination may leave a large number of rabbits unprotected following vaccine administration. Successful vaccination requires the strict implication of workable, planned, on farm programs. Following this, analysis to confirm seroconversion rates may be advisable. Factors such as the wild rabbit reservoir, control of biting insects and good hygienic practices must be taken into consideration to prevent vaccine failures from occurring. Copyright © 2015 Elsevier B.V. All rights reserved.
Demeure, Christian E; Derbise, Anne; Carniel, Elisabeth
Yersinia pestis, the agent of plague, is among the deadliest bacterial pathogens affecting humans, and is a potential biological weapon. Because antibiotic resistant strains of Yersinia pestis have been observed or could be engineered for evil use, vaccination against plague might become the only means to reduce mortality. Although plague is re-emerging in many countries, a vaccine with worldwide license is currently lacking. The vaccine strategy described here is based on an oral vaccination with an attenuated strain of Yersinia pseudotuberculosis. Indeed, this species is genetically almost identical to Y. pestis, but has a much lower pathogenicity and a higher genomic stability. Gradual modifications of the wild-type Yersinia pseudotuberculosis strain IP32953 were performed to generate a safe and immunogenic vaccine. Genes coding for three essential virulence factors were deleted from this strain. To increase cross-species immunogenicity, an F1-encapsulated Y. pseudotuberculosis strain was then generated. For this, the Y. pestis caf operon, which encodes F1, was inserted first on a plasmid, and subsequently into the chromosome. The successive steps achieved to reach maximal vaccine potential are described, and how each step affected bacterial virulence and the development of a protective immune response is discussed. The final version of the vaccine, named VTnF1, provides a highly efficient and long-lasting protection against both bubonic and pneumonic plague after a single oral vaccine dose. Since a Y. pestis strain deprived of F1 exist or could be engineered, we also analyzed the protection conferred by the vaccine against such strain and found that it also confers full protection against the two forms of plague. Thus, the properties of VTnF1 makes it one of the most efficient candidate vaccine for mass vaccination in tropical endemic areas as well as for populations exposed to bioterrorism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Beck, Andrew S; Barrett, Alan D T
Yellow fever 17D vaccine is one of the oldest live-attenuated vaccines in current use that is recognized historically for its immunogenic and safe properties. These unique properties of 17D are presently exploited in rationally designed recombinant vaccines targeting not only flaviviral antigens but also other pathogens of public health concern. Several candidate vaccines based on 17D have advanced to human trials, and a chimeric recombinant Japanese encephalitis vaccine utilizing the 17D backbone has been licensed. The mechanism(s) of attenuation for 17D are poorly understood; however, recent insights from large in silico studies have indicated particular host genetic determinants contributing to the immune response to the vaccine, which presumably influences the considerable durability of protection, now in many cases considered to be lifelong. The very rare occurrence of severe adverse events for 17D is discussed, including a recent fatal case of vaccine-associated viscerotropic disease.
Beck, Andrew S.; Barrett, Alan D.T.
Summary Yellow fever 17D vaccine is one of the oldest live-attenuated vaccines in current use that is recognized for historically immunogenic and safe properties. These unique properties of 17D are presently exploited in rationally designed recombinant vaccines targeting not only flaviviral antigens but also other pathogens of public health concern. Several candidate vaccines based on 17D have advanced to human trials, and a chimeric recombinant Japanese encephalitis vaccine utilizing the 17D backbone has been licensed. The mechanism(s) of attenuation for 17D are poorly understood; however, recent insights from large in silico studies have indicated particular host genetic determinants contributing to the immune response to the vaccine, which presumably influences the considerable durability of protection, now in many cases considered to be life-long. The very rare occurrence of severe adverse events for 17D is discussed, including a recent fatal case of vaccine-associated viscerotropic disease. PMID:26366673
Full Text Available Despite advancements in immunotherapeutic approaches, influenza continues to cause severe illness, particularly among immunocompromised individuals, young children, and elderly adults. Vaccination is the most effective way to reduce rates of morbidity and mortality caused by influenza viruses. Frequent genetic shift and drift among influenza-virus strains with the resultant disparity between circulating and vaccine virus strains limits the effectiveness of the available conventional influenza vaccines. One approach to overcome this limitation is to develop a universal influenza vaccine that could provide protection against all subtypes of influenza viruses. Moreover, the development of a novel or improved universal influenza vaccines may be greatly facilitated by new technologies including virus-like particles, T-cell-inducing peptides and recombinant proteins, synthetic viruses, broadly neutralizing antibodies, and nucleic acid-based vaccines. This review discusses recent scientific advances in the development of next-generation universal influenza vaccines.
Hotez, Peter J; Bottazzi, Maria Elena; Strych, Ulrich
The 2000 Millennium Development Goals helped stimulate the development of life-saving childhood vaccines for pneumococcal and rotavirus infections while greatly expanding coverage of existing vaccines. However, there remains an urgent need to develop new vaccines for HIV/AIDS, malaria, and tuberculosis, as well as for respiratory syncytial virus and those chronic and debilitating (mostly parasitic) infections known as neglected tropical diseases (NTDs). The NTDs represent the most common diseases of people living in extreme poverty and are the subject of this review. The development of NTD vaccines, including those for hookworm infection, schistosomiasis, leishmaniasis, and Chagas disease, is being led by nonprofit product development partnerships (PDPs) working in consortia of academic and industrial partners, including vaccine manufacturers in developing countries. NTD vaccines face unique challenges with respect to their product development and manufacture, as well as their preclinical and clinical testing. We emphasize global efforts to accelerate the development of NTD vaccines and some of the hurdles to ensuring their availability to the world's poorest people.
To avoid the risk of vaccine-associated paralytic poliomyelitis (VAPP) and polio outbreaks due to circulating vaccine-derived polioviruses, an inactivated poliovirus vaccine (IPV) was introduced for routine immunization in a number of countries with a low risk of polio outbreaks. Currently, production and marketing of a standalone conventional IPV and two diphtheria-pertussis-tetanus-IPV (Sabin-derived IPV; sIPV) products have been submitted, and it is expected that the IPV products will be introduced in Japan in the autumn of 2012. At the same time, a decline in the OPV immunization rate became apparent in Japan due to serious public concerns about a remaining risk of VAPP and introduction of IPV in the near future. Therefore, the recent development of polio immunity gaps should be carefully monitored, and surveillance of suspected polio cases and laboratory diagnosis of polioviruses have to be intensified for the transition period from OPV to IPV in Japan. The development of sIPV is one of the most realistic options to introduce affordable IPV to developing countries. In this regard, further clinical studies on its efficacy, safety, and interchangeability of sIPV will be needed after the introduction of the sIPV products, which will be licensed in Japan for the first time in the world.
Petrovskaia, V G; Marakusha, B I; Bondarenko, V M
The presently known methods of obtaining Salmonella vaccine strains are characterized, their advantages and drawbacks are noted. Great importance of the genetic safety of Salmonella attenuated strains to be controlled is emphasized, taking into account that they are also used as carrier strains for obtaining hybrid and gene-engineering (vector) vaccines carrying immunogenicity factors of other species of pathogenic microorganisms.
... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)
Maria Goretti P Fonseca
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.
Partial Contents: AIDS in Burundi, Rwanda AIDS Situation in Country Examined, Estimated Over 750,000 HIV Positive, In 3 Years 4 Million May Be AIDS Carriers, Events at National AIDS Convention Analyzed, Senior Army...
Background Vaccine literature indexing is poorly performed in PubMed due to limited hierarchy of Medical Subject Headings (MeSH) annotation in the vaccine field. Vaccine Ontology (VO) is a community-based biomedical ontology that represents various vaccines and their relations. SciMiner is an in-house literature mining system that supports literature indexing and gene name tagging. We hypothesize that application of VO in SciMiner will aid vaccine literature indexing and mining of vaccine-gene interaction networks. As a test case, we have examined vaccines for Brucella, the causative agent of brucellosis in humans and animals. Results The VO-based SciMiner (VO-SciMiner) was developed to incorporate a total of 67 Brucella vaccine terms. A set of rules for term expansion of VO terms were learned from training data, consisting of 90 biomedical articles related to Brucella vaccine terms. VO-SciMiner demonstrated high recall (91%) and precision (99%) from testing a separate set of 100 manually selected biomedical articles. VO-SciMiner indexing exhibited superior performance in retrieving Brucella vaccine-related papers over that obtained with MeSH-based PubMed literature search. For example, a VO-SciMiner search of "live attenuated Brucella vaccine" returned 922 hits as of April 20, 2011, while a PubMed search of the same query resulted in only 74 hits. Using the abstracts of 14,947 Brucella-related papers, VO-SciMiner identified 140 Brucella genes associated with Brucella vaccines. These genes included known protective antigens, virulence factors, and genes closely related to Brucella vaccines. These VO-interacting Brucella genes were significantly over-represented in biological functional categories, including metabolite transport and metabolism, replication and repair, cell wall biogenesis, intracellular trafficking and secretion, posttranslational modification, and chaperones. Furthermore, a comprehensive interaction network of Brucella vaccines and genes were
Full Text Available Mucosal vaccines created on the base of transgenic plants reacting with mucosal layers of the intestines and other organs are considered to be the perspective method of the vaccination. These vaccines induce both mucosal and general humoral immunogenicity after the peroral administration. The folding of antigenic proteins synthesizing in plants occurs via eukaryotic type and has advantages before yeast and prokaryotic platforms. This feature results to more adequate synthesis of antibodies against pathogens and to the interaction with effector molecules of complement. Earlier we together with The State Scientific Center “Vector”, Institute of chemical biology and fundamental medicine SB RAS and Dr R.Hammond from Laboratory of Plant Pathology (Maryland, USA created two candidate vaccines : one of them against AIDS (HIV-1 and hepatitis B on the base of the chimeric gene TBI-HBS, encoding simultaneously 9 antigenic determinants of HIV-1 and the main surface antigen of hepatitis B (HBsAg. The second candidate vaccine was created against hepatitis B on the base of the genetic construct with the gene preS2-S encoding the synthesis of two subunits of the main surface antigen of hepatitis B and the signal peptide HDEL which directed antigens for the accumulation on ER. Both vaccines were tested on mice and confirmed their immunogenicity as the pronounced antibodies response. Twice vaccinated mice maintained the antibodies response during 11 months after there was little tendency to lowering. It was established that transgenic plants – vaccines (tomato kept the capability to the synthesis of antigenic determinants in seven seed generations during 7 years. The results of the development of the mucosal vaccine against cervical carcinoma (carcinoma of uterine cervix evoked by human papillomaviruses of high oncogenic risks were presented in this report. We created the genetic construct consisting of 35S CaMV promoter, Ώ (omega leader of TMV, the
E M D L van der Heijden
Full Text Available Conventional control and eradication strategies for bovine tuberculosis (BTB face tremendous difficulties in developing countries; countries with wildlife reservoirs, a complex wildlife-livestock-human interface or a lack of veterinary and veterinary public health surveillance. Vaccination of cattle and other species might in some cases provide the only suitable control strategy for BTB, while in others it may supplement existing test-and-slaughter schemes. However, the use of live BCG has several limitations and the global rise of HIV/AIDS infections has furthermore warranted the exploration of inactivated vaccine preparations. The aim of this study was to compare the immune response profiles in response to parenteral vaccination with live BCG and two inactivated vaccine candidates in cattle. Twenty-four mixed breed calves (Bos taurus aged 4-6 months, were allocated to one of four groups and vaccinated sub-cutaneously with live M. bovis BCG (Danish 1331, formalin-inactivated M. bovis BCG, heat-killed M. bovis or PBS/Montanide™ (control. Interferon-γ responsiveness and antibody production were measured prior to vaccination and at weekly intervals thereafter for twelve weeks. At nine weeks post-priming, animals were skin tested using tuberculins and MTBC specific protein cocktails and subsequently challenged through intranodular injection of live M. bovis BCG. The animals in the heat-killed M. bovis group demonstrated strong and sustained cell-mediated and humoral immune responses, significantly higher than the control group in response to vaccination, which may indicate a protective immune profile. Animals in this group showed reactivity to the skin test reagents, confirming good vaccine take. Lastly, although not statistically significant, recovery of BCG after challenge was lowest in the heat-killed M. bovis group. In conclusion, the parenteral heat-killed M. bovis vaccine proved to be clearly immunogenic in cattle in the present study
Kennedy, Catriona; Gray Brunton, Carol; Hogg, Rhona
Parental decision making about childhood vaccinations is complex and the vaccination schedule ever-changing. Vaccination may be controversial even in countries with historically high vaccination rates such as Scotland. Health behaviour models have aided understanding of individual vaccine intentions for specific vaccines. These are limited in explaining actual behaviours and are divorced from the impact of socio-cultural contexts on vaccination decision making. To explore vaccination views in Scotland amongst parents, teenage girls and health professionals across three controversial vaccines: the Measles, Mumps, Rubella (MMR), the Human Papilloma virus (HPV) and the Influenza A (H1N1) vaccine. We used qualitative interviews and focus group discussions in a purposive sample of health professionals (n = 51), parents (n = 15) and teenage girls aged 12-15 years (n = 8) about their views of these vaccines. Discussions were analysed using thematic analysis. Two main themes are highlighted: 'vaccine risks revisited' in which we explored how the MMR legacy resurfaced and how worries about vaccine safety permeated the data. 'Vaccine responsibilities' indicated tensions regarding roles and responsibilities for vaccines. An overarching notion of 'just that little bit of doubt' referred to lingering doubts and uncertainties interwoven across the vaccines. Public health authorities should remain alert towards pervasive vaccine concerns. It is important for authorities to clarify vaccine roles and responsibilities in the face of new and existing vaccines and to acknowledge public concerns regarding vaccine safety.
Full Text Available Background: Although rigorous efforts have substantially decreased the malaria burden through decades, it still threatens the lives of millions of children. Development of an effective vaccine can provide important approach in malaria control strategies. Unfortunately, development of an effective vaccine for falciparum malaria has been hindered by the extreme complexity of malaria parasite biology, complex and diverse parasite genomes, and immune evasion by the parasites as well as the intricate nature of the parasites infection cycle. The aim of this review was to discuss the different approaches to malaria vaccine development until now.Methods: Scientific databases, including MEDLINE (via PubMed and SCOPUS were searched up to 30 Jan 2017 and the articles regarding malaria vaccine development were taken into examination.Results: Several strategies for malaria vaccine development including pre-erythrocytic vaccines, antibody-based subunit vaccines, vectored vaccines, whole sporozoite vaccines, genetically Attenuated parasites and sporozoite subunit vaccine, erythrocytic vaccines, sexual stage vaccine, transmission-blocking vaccine as well as synthetic peptides and conjugate vaccine has been introduced. However, the success has been limited thus far.Conclusion: Although development of malaria vaccine over the past 70 year has been continued, the discovery, development, and licensing of a malaria vaccine formulation, which meets safety, affordability, accessibility, applicability, and efficacy has not yet been achieved.
Nielsen, Henriette S.; Oleksiewicz, Martin B; Forsberg, R
A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates was sequen......A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates...... in the vaccine virus sequence during cell-culture adaptation. Evaluation of the remaining mutations in the ORF1 sequence revealed stronger selective pressure for amino acid conservation during spread in pigs than during vaccine production. Furthermore, it was found that the selective pressure did not change...
Nielsen, Henriette S.; Oleksiewicz, M.B.; Forsberg, R.
A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates was sequen......A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates...... in the vaccine virus sequence during cell-culture adaptation. Evaluation of the remaining mutations in the ORF1 sequence revealed stronger selective pressure for amino acid conservation during spread in pigs than during vaccine production. Furthermore, it was found that the selective pressure did not change...
Bissett, Sara L; Godi, Anna; Jit, Mark; Beddows, Simon
Human papillomavirus vaccines have demonstrated remarkable efficacy against persistent infection and disease associated with vaccine-incorporated genotypes and a degree of efficacy against some genetically related, non-vaccine-incorporated genotypes. The vaccines differ in the extent of cross-protection against these non-vaccine genotypes. Data supporting the role for neutralizing antibodies as a correlate or surrogate of cross-protection are lacking, as is a robust assessment of the seroconversion rates against these non-vaccine genotypes. We performed a systematic review and meta-analysis of available data on vaccine-induced neutralizing antibody seropositivity to non-vaccine incorporated HPV genotypes. Of 304 articles screened, 9 were included in the analysis representing ca. 700 individuals. The pooled estimate for seropositivity against HPV31 for the bivalent vaccine (86%; 95%CI 78-91%) was higher than that for the quadrivalent vaccine (61%; 39-79%; p=0.011). The pooled estimate for seropositivity against HPV45 for the bivalent vaccine (50%; 37-64%) was also higher than that for the quadrivalent vaccine (16%; 6-36%; p=0.007). Seropositivity against HPV33, HPV52 and HPV58 were similar between the vaccines. Mean seropositivity rates across non-vaccine genotypes were positively associated with the corresponding vaccine efficacy data reported from vaccine trials. These data improve our understanding of vaccine-induced functional antibody specificity against non-vaccine incorporated genotypes and may help to parameterize vaccine-impact models and improve patient management in a post-vaccine setting. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.
Van Reeth, Kristien; Ma, Wenjun
Commercial vaccines currently available against swine influenza virus (SIV) are inactivated, adjuvanted, whole virus vaccines, based on H1N1 and/or H3N2 and/or H1N2 SIVs. In keeping with the antigenic and genetic differences between SIVs circulating in Europe and the US, the vaccines for each region are produced locally and contain different strains. Even within a continent, there is no standardization of vaccine strains, and the antigen mass and adjuvants can also differ between different commercial products. Recombinant protein vaccines against SIV, vector, and DNA vaccines, and vaccines attenuated by reverse genetics have been tested in experimental studies, but they have not yet reached the market. In this review, we aim to present a critical analysis of the performance of commercial inactivated and novel generation SIV vaccines in experimental vaccination challenge studies in pigs. We pay special attention to the differences between commercial SIV vaccines and vaccination attitudes in Europe and in North America, to the issue of vaccine strain selection and changes, and to the potential advantages of novel generation vaccines over the traditional killed SIV vaccines.
Brueggemann, Angela B; Pai, Rekha; Crook, Derrick W; Beall, Bernard
The heptavalent pneumococcal conjugate vaccine (PCV7) was introduced in the United States (US) in 2000 and has significantly reduced invasive pneumococcal disease; however, the incidence of nonvaccine serotype invasive disease, particularly due to serotype 19A, has increased. The serotype 19A increase can be explained in part by expansion of a genotype that has been circulating in the US prior to vaccine implementation (and other countries since at least 1990), but also by the emergence of a novel "vaccine escape recombinant" pneumococcal strain. This strain has a genotype that previously was only associated with vaccine serotype 4, but now expresses a nonvaccine serotype 19A capsule. Based on prior evidence for capsular switching by recombination at the capsular locus, the genetic event that resulted in this novel serotype/genotype combination might be identifiable from the DNA sequence of individual pneumococcal strains. Therefore, the aim of this study was to characterise the putative recombinational event(s) at the capsular locus that resulted in the change from a vaccine to a nonvaccine capsular type. Sequencing the capsular locus flanking regions of 51 vaccine escape (progeny), recipient, and putative donor pneumococci revealed a 39 kb recombinational fragment, which included the capsular locus, flanking regions, and two adjacent penicillin-binding proteins, and thus resulted in a capsular switch and penicillin nonsusceptibility in a single genetic event. Since 2003, 37 such vaccine escape strains have been detected, some of which had evolved further. Furthermore, two new types of serotype 19A vaccine escape strains emerged in 2005. To our knowledge, this is the first time a single recombinational event has been documented in vivo that resulted in both a change of serotype and penicillin nonsusceptibility. Vaccine escape by genetic recombination at the capsular locus has the potential to reduce PCV7 effectiveness in the longer term.
Saluja, Vinay; Hinrichs, Wouter L. J.; Frijlink, Henderik W.
Since last year influenza pandemic has struck again after 40 years, this is the right moment to discuss the different available formulation options for influenza vaccine. Looking back to the last 4 decades, most vaccines are still formulated as liquid solution. These vaccines have shown a poor
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.
... high or when infection would pose a high risk to the mother or baby, vaccination with a live vaccine is discussed. If there ... and benefits. For some diseases the benefit of vaccination outweighs any risks that may be associated with the vaccine. What ...
Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.
Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.
Combination vaccines have been introduced in Mexico. The national immunization program has incorporated the measles-mumps-rubella (MMR) vaccines in 1998, and the pentavalent vaccine in 1999. The two categories of antigen composition in combination vaccines are: 1) multiple different antigenic types of a single pathogen, such as the 23 valent pneumococcal polysaccharide vaccine, and 2) antigens from different pathogens causing different diseases, such as the DPT and MMR vaccines. Pentavalent vaccines are included in the second category. The vaccine protects against diphtheria, tetanus, pertussis, hepatitis B, and other diseases produced by Haemophilus influenzae type b (Hib). Combined diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenza type b (DTP-HB/Hib) vaccine has been distributed to 87% of Mexican children under 1 year of age. Over 800,000 doses of pentavalent vaccine have been administered.
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.
Full Text Available Novel efficient vaccines are needed to control tuberculosis (TB, a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine. In this review we provide up to date information on novel tuberculosis (TB vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed.
Leunda, Amaya; Baldo, Aline; Goossens, Martine; Huygen, Kris; Herman, Philippe; Romano, Marta
Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine). In this review we provide up to date information on novel tuberculosis (TB) vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO) which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed.
Leunda, Amaya; Baldo, Aline; Goossens, Martine; Huygen, Kris; Herman, Philippe; Romano, Marta
Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine). In this review we provide up to date information on novel tuberculosis (TB) vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO) which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed. PMID:26344627
Embregts, Carmen W.E.; Forlenza, Maria
The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen breakdown in the harsh gastric environment, but also to the high tolerogenic gut environment and to inadequate vaccine design. In this review we discuss current approaches used to develop oral vaccines fo...
Ahmed, S. Sohail; Black, Steve; Ulmer, Jeffrey
Summary This minireview will provide a perspective on new developments and concepts related to biomarker applications for vaccines. In the context of preventive vaccines, biomarkers have the potential to predict adverse events in select subjects due to differences in genetic make‐up/underlying medical conditions or to predict effectiveness (good versus poor response). When expanding them to therapeutic vaccines, their utility in identification of patients most likely to respond favourably (or avoid potentially negative effects of treatment) becomes self‐explanatory. Despite the progress made so far on dissection of various pathways of biological significance in humans, there is still plenty to unravel about the mysteries related to the quantitative and qualitative aspects of the human host response. This review will provide a focused overview of new concepts and developments in the field of vaccine biomarkers including (i) vaccine‐dependent signatures predicting subject response and safety, (ii) predicting therapeutic vaccine efficacy in chronic diseases, (iii) exploring the genetic make‐up of the host that may modulate subject‐specific adverse events or affect the quality of immune responses, and (iv) the topic of volunteer stratification as a result of biomarker screening (e.g. for therapeutic vaccines but also potentially for preventive vaccines) or as a reflection of an effort to compare select groups (e.g. vaccinated subjects versus patients recovering from infection) to enable the discovery of clinically relevant biomarkers for preventive vaccines. PMID:21895991
Murray E. Hines
Full Text Available Johne’s disease (JD caused by Mycobacterium avium subspecies paratuberculosis (MAP is a major threat to the dairy industry and possibly some cases of Crohn’s disease in humans. A MAP vaccine that reduced of clinical disease and/or reduced fecal shedding would aid in the control of JD. The objectives of this study were 1 to evaluate the efficacy of 5 attenuated strains of MAP as vaccine candidates compared to a commercial control vaccine using the protocol proposed by the Johne’s Disease Integrated Program (JDIP Animal Model Standardization Committee (AMSC, and 2 to validate the AMSC Johne’s disease goat challenge model. Eighty goat kids were vaccinated orally twice at 8 and 10 weeks of age with an experimental vaccine or once subcutaneously at 8 weeks with Silirum® (Zoetis, or a sham control oral vaccine at 8 and 10 weeks. Kids were challenged orally with a total of approximately 1.44 X 10^9 CFU divided in 2 consecutive daily doses using MAP ATCC-700535 (K10-like bovine isolate. All kids were necropsied at 13 months post challenge. Results indicated that the AMSC goat challenge model is a highly efficient and valid model for JD challenge studies. None of the experimental or control vaccines evaluated prevented MAP infection or eliminated fecal shedding, although the 329 vaccine lowered the incidence of infection, fecal shedding, tissue colonization and reduced lesion scores, but less than the control vaccine. Based on our results the relative performance ranking of the experimental live-attenuated vaccines evaluated, the 329 vaccine was the best performer, followed by the 318 vaccine, then 316 vaccine, 315 vaccine and finally the 319 vaccine was the worst performer. The subcutaneously injected control vaccine outperformed the orally-delivered mutant vaccine candidates. Two vaccines (329 and 318 do reduce presence of JD gross and microscopic lesions, slow progression of disease, and one vaccine (329 reduced fecal shedding and tissue
Hines, Murray E.; Turnquist, Sue E.; Ilha, Marcia R. S.; Rajeev, Sreekumari; Jones, Arthur L.; Whittington, Lisa; Bannantine, John P.; Barletta, Raúl G.; Gröhn, Yrjö T.; Katani, Robab; Talaat, Adel M.; Li, Lingling; Kapur, Vivek
Johne's disease (JD) caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a major threat to the dairy industry and possibly some cases of Crohn's disease in humans. A MAP vaccine that reduced of clinical disease and/or reduced fecal shedding would aid in the control of JD. The objectives of this study were (1) to evaluate the efficacy of 5 attenuated strains of MAP as vaccine candidates compared to a commercial control vaccine using the protocol proposed by the Johne's Disease Integrated Program (JDIP) Animal Model Standardization Committee (AMSC), and (2) to validate the AMSC Johne's disease goat challenge model. Eighty goat kids were vaccinated orally twice at 8 and 10 weeks of age with an experimental vaccine or once subcutaneously at 8 weeks with Silirum® (Zoetis), or a sham control oral vaccine at 8 and 10 weeks. Kids were challenged orally with a total of approximately 1.44 × 109 CFU divided in two consecutive daily doses using MAP ATCC-700535 (K10-like bovine isolate). All kids were necropsied at 13 months post-challenge. Results indicated that the AMSC goat challenge model is a highly efficient and valid model for JD challenge studies. None of the experimental or control vaccines evaluated prevented MAP infection or eliminated fecal shedding, although the 329 vaccine lowered the incidence of infection, fecal shedding, tissue colonization and reduced lesion scores, but less than the control vaccine. Based on our results the relative performance ranking of the experimental live-attenuated vaccines evaluated, the 329 vaccine was the best performer, followed by the 318 vaccine, then 316 vaccine, 315 vaccine and finally the 319 vaccine was the worst performer. The subcutaneously injected control vaccine outperformed the orally-delivered mutant vaccine candidates. Two vaccines (329 and 318) do reduce presence of JD gross and microscopic lesions, slow progression of disease, and one vaccine (329) reduced fecal shedding and tissue colonization. PMID
Date, Kashmira A; Bentsi-Enchill, Adwoa; Marks, Florian; Fox, Kimberley
Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control. Copyright © 2015. Published by
First aid Animal bites: First aid Animal bites: First aid By Mayo Clinic Staff These guidelines can help you care for a minor animal bite, such ... 26, 2017 Original article: http://www.mayoclinic.org/first-aid/first-aid-animal-bites/basics/ART-20056591 . Mayo ...
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First aid Head trauma: First aid Head trauma: First aid By Mayo Clinic Staff Most head trauma involves injuries that are minor and don't require ... 21, 2015 Original article: http://www.mayoclinic.org/first-aid/first-aid-head-trauma/basics/ART-20056626 . Mayo ...
Resources - HIV/AIDS ... information on AIDS : AIDS.gov -- www.aids.gov AIDS Info -- aidsinfo.nih.gov The Henry J. Kaiser Family Foundation -- www.kff.org/hivaids US Centers for Disease Control and Prevention -- www.cdc.gov/hiv
Johansen, H.K.; Gøtzsche, Peter C.; Johansen, Helle Krogh
BACKGROUND: Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. OBJECTIVES......: To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search May 2008) and PubMed using the terms vaccin* AND cystic...... fibrosis (last search May 2008). SELECTION CRITERIA: Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently selected trials...
Johansen, Helle Krogh; Gøtzsche, Peter C
BACKGROUND: Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed....... This is an update of a previously published review. OBJECTIVES: To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30...... March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013). SELECTION CRITERIA: Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic...
WHEELER COSETTE M
Full Text Available The potential use of vaccines for the human papillomavirus (HPV in the prevention and treatment of cervical cancer is a possibility in the near future. Close to 20 genotypes of HPV, of the 75 that have been identified, infect the femine genital tract, but four subtypes (16, 18, 31 and 45 have been associated in close to 80% of cervical cancers. this article proposes that in order to design an effective prophylactic vaccine against HPV infection, an adequate immune response should be guaranteed through four goals; a activation of antigens present in the cell; b overcoming the host response and viral genetic variability in the T cell response; c generation of high levels of T and B memory cells; and d persistence of antigens.
Hjertholm, Peter; Laursen, Jytte; White, Howard
foreign aid, macroeconomics of aid, gap models, aid fungibility, fiscal response models, foreign debt,......foreign aid, macroeconomics of aid, gap models, aid fungibility, fiscal response models, foreign debt,...
Alsahli, M; Farrell, R J; Michetti, P
Over the past decade, intensive research has focused on developing a vaccine therapy for Helicobacter pylori. Substantial unresolved questions cloud the current approach, and the development of a vaccine against this unique organism has proved very challenging. Many candidate vaccines have been tested in animal models. The immunogenicity and the safety of some vaccine formulations have been recently evaluated through clinical trials, and the efficacy of these vaccine therapies in humans will be determined in the near future. This article will provide an overview of the current knowledge of natural and vaccine-induced immune responses to H. pylori infection. It will also review past vaccine successes and failures in animal models and the limited experience to date in using vaccine therapy in humans. Several obstacles to H. pylori vaccine development efforts along with the future direction of these efforts will be discussed. Copyright 2001 S. Karger AG, Basel
Miravalle, Augusto A; Schreiner, Teri
This chapter reviews the most common neurologic disorders associated with common vaccines, evaluates the data linking the disorder with the vaccine, and discusses the potential mechanism of disease. A literature search was conducted in PubMed using a combination of the following terms: vaccines, vaccination, immunization, and neurologic complications. Data were also gathered from publications of the American Academy of Pediatrics Committee on Infectious Diseases, the World Health Organization, the US Centers for Disease Control and Prevention, and the Vaccine Adverse Event Reporting System. Neurologic complications of vaccination are rare. Many associations have been asserted without objective data to support a causal relationship. Rarely, patients with a neurologic complication will have a poor outcome. However, most patients recover fully from the neurologic complication. Vaccinations have altered the landscape of infectious disease. However, perception of risk associated with vaccinations has limited the success of disease eradication measures. Neurologic complications can be severe, and can provoke fear in potential vaccines. Evaluating whether there is causal link between neurologic disorders and vaccinations, not just temporal association, is critical to addressing public misperception of risk of vaccination. Among the vaccines available today, the cost-benefit analysis of vaccinations and complications strongly argues in favor of vaccination. © 2014 Elsevier B.V. All rights reserved.
... Hepatitis A vaccine supply in the US. Updated Mar 2018 Note 2 : Pediatric hepatitis B vaccine: Merck ... Submitted, Licensed, and Recommended Vaccines & Biologics Red Book® Online Influenza Vaccination Recommendations Childhood & Adolescent Immunization Schedules Adult ...
... Work Importance of Vaccines Paying for Vaccines State Immunization Programs Tips for Finding Vaccine Records Trusted Sources of ... efficacy, and use of vaccines within the broad immunization community of patients, parents, healthcare organizations, and government health agencies.
Hickling, JK; Jones, KR; Friede, M; Chen, D; Kristensen, D
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
Khamesipour, Ali; Rafati, Sima; Davoudi, Noushin; Maboudi, Fereidoun; Modabber, Farrokh
A vaccine against different forms of leishmaniasis should be feasible considering the wealth of information on genetics and biology of the parasite, clinical and experimental immunology of leishmaniasis, and the availability of vaccines that can protect experimental animals against challenge with different Leishmania species. However, there is no vaccine against any form of leishmaniasis for general human use. One major factor is the lack of a conceived market for human leishmaniasis vaccines. Hence pharmaceutical industries involved in vaccine development are not interested in investing millions of dollars and a decade that is required for developing a new vaccine. Besides, leishmaniasis is a local/regional problem and not a global one. According to the estimates of the World Health Organization, 90 per cent of visceral leishmaniasis occurs in five countries (Bangladesh, Brazil, India, Nepal and Sudan). Those in need are amongst the poorest people in these countries. It should therefore be the objectives of these countries to develop a vaccine. Fortunately, both Brazil and India have designated the control of visceral leishmaniasis as a top priority for their respective Ministries of Health. The purpose of this review is to present only the vaccines in use and those in development for use in dogs or humans. This is not an exhaustive review of vaccine discovery or the principles of clinical immunology underlying vaccine development.
... Coinfection Hepatitis C Coinfection HIV/AIDS Coinfection HIV/AIDS Coinfection Approximately 10% of the HIV-infected population ... Control and Prevention website to learn about HIV/AIDS and Viral Hepatitis guidelines and resources. Home About ...
First aid Gastroenteritis: First aid Gastroenteritis: First aid By Mayo Clinic Staff Gastroenteritis is an inflammation of your stomach and intestines. Common causes are: Viruses. Food or water contaminated by ...
First aid Snakebites: First aid Snakebites: First aid By Mayo Clinic Staff Most North American snakes aren't dangerous to humans. Some exceptions include the rattlesnake, coral snake, water moccasin ...
... Staying Safe Videos for Educators Search English Español HIV and AIDS KidsHealth / For Kids / HIV and AIDS ... actually the virus that causes the disease AIDS. HIV Hurts the Immune System People who are HIV ...
... the aids? Start using your hearing aids in quiet surroundings, gradually building up to noisier environments. Then eventually work up to wearing your hearing aids all waking hours. Keep a diary to help you remember your ...
First aid - heart attack; First aid - cardiopulmonary arrest; First aid - cardiac arrest ... A heart attack occurs when the blood flow that carries oxygen to the heart is blocked. The heart muscle ...
van Dalen, H.P.; Reuser, M.
Development assistance targeting health overwhelmingly concentrates on HIV/AIDS. This column argues that that focus neglects critical demographic issues and degrades health infrastructure, particularly in Sub-Saharan Africa. The prime rule for AIDS aid should be “First, do no harm”.
Full Text Available Most of the cases of vaccine associated myocarditis have been following small pox vaccination. Reports have also been there after streptococcal pneumonia vaccine and influenza vaccine. In some cases, autoimmune/inflammatory syndrome induced by adjuvants (ASIA used in the vaccine have been implicated. Exclusion of other causes is very important in the diagnostic process, especially that of acute coronary syndrome. Management is similar to that of other etiologies of myocarditis. These rare instances of myocarditis should not preclude one from taking necessary immunization for vaccine preventable diseases.
Hogue, Michael D; Meador, Anna E
Vaccines are among most cost-effective public health strategies. Despite effective vaccines for many bacterial and viral illnesses, tens of thousands of adults and hundreds of children die each year in the United States from vaccine-preventable diseases. Underutilization of vaccines requires rethinking the approach to incorporating vaccines into practice. Arguably, immunizations could be a part all health care encounters. Shared responsibility is paramount if deaths are to be reduced. This article reviews the available vaccines in the US market, as well as practice recommendations of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. Copyright © 2016 Elsevier Inc. All rights reserved.
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 M?rieux are known among experts only despite their contribution to global hea...
Duan, Zhiqiang; Xu, Houqiang; Ji, Xinqin; Zhao, Jiafu
Recent advances in recombinant genetic engineering techniques have brought forward a leap in designing new vaccines in modern medicine. One attractive strategy is the application of reverse genetics technology to make recombinant Newcastle disease virus (rNDV) deliver protective antigens of pathogens. In recent years, numerous studies have demonstrated that rNDV-vectored vaccines can induce quicker and better humoral and mucosal immune responses than conventional vaccines and are protective against pathogen challenges. With deeper understanding of NDV molecular biology, it is feasible to develop gene-modified rNDV vaccines accompanied by good safety, high efficacy, low toxicity and better immunogenicity. This review summarizes the development of reverse genetics technology in using NDV as a promising vaccine vector to design new vaccines for human and animal use.
Crépey, P.; De Boer, P.; Postma, M.J.; Pitman, R.J.
Objectives: Vaccination has proven to be an efficient preventive strategy against influenza infection. Each year, two genetically distinct influenza B lineages cocirculate. Current trivalent influenza vaccines (TIVs) contain only one influenza B and two influenza A strains, but vaccine mismatch are
Chen, Tao; Dredze, Mark
Visual imagery plays a key role in health communication; however, there is little understanding of what aspects of vaccine-related images make them effective communication aids. Twitter, a popular venue for discussions related to vaccination, provides numerous images that are shared with tweets. The objectives of this study were to understand how images are used in vaccine-related tweets and provide guidance with respect to the characteristics of vaccine-related images that correlate with the higher likelihood of being retweeted. We collected more than one million vaccine image messages from Twitter and characterized various properties of these images using automated image analytics. We fit a logistic regression model to predict whether or not a vaccine image tweet was retweeted, thus identifying characteristics that correlate with a higher likelihood of being shared. For comparison, we built similar models for the sharing of vaccine news on Facebook and for general image tweets. Most vaccine-related images are duplicates (125,916/237,478; 53.02%) or taken from other sources, not necessarily created by the author of the tweet. Almost half of the images contain embedded text, and many include images of people and syringes. The visual content is highly correlated with a tweet's textual topics. Vaccine image tweets are twice as likely to be shared as nonimage tweets. The sentiment of an image and the objects shown in the image were the predictive factors in determining whether an image was retweeted. We are the first to study vaccine images on Twitter. Our findings suggest future directions for the study and use of vaccine imagery and may inform communication strategies around vaccination. Furthermore, our study demonstrates an effective study methodology for image analysis. ©Tao Chen, Mark Dredze. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 03.04.2018.
Background Visual imagery plays a key role in health communication; however, there is little understanding of what aspects of vaccine-related images make them effective communication aids. Twitter, a popular venue for discussions related to vaccination, provides numerous images that are shared with tweets. Objective The objectives of this study were to understand how images are used in vaccine-related tweets and provide guidance with respect to the characteristics of vaccine-related images that correlate with the higher likelihood of being retweeted. Methods We collected more than one million vaccine image messages from Twitter and characterized various properties of these images using automated image analytics. We fit a logistic regression model to predict whether or not a vaccine image tweet was retweeted, thus identifying characteristics that correlate with a higher likelihood of being shared. For comparison, we built similar models for the sharing of vaccine news on Facebook and for general image tweets. Results Most vaccine-related images are duplicates (125,916/237,478; 53.02%) or taken from other sources, not necessarily created by the author of the tweet. Almost half of the images contain embedded text, and many include images of people and syringes. The visual content is highly correlated with a tweet’s textual topics. Vaccine image tweets are twice as likely to be shared as nonimage tweets. The sentiment of an image and the objects shown in the image were the predictive factors in determining whether an image was retweeted. Conclusions We are the first to study vaccine images on Twitter. Our findings suggest future directions for the study and use of vaccine imagery and may inform communication strategies around vaccination. Furthermore, our study demonstrates an effective study methodology for image analysis. PMID:29615386
Mumpsvax® Mumps Vaccine ... Biavax® II (as a combination product containing Mumps Vaccine, Rubella Vaccine) ... II (as a combination product containing Measles Vaccine, Mumps Vaccine, Rubella Vaccine)
... Entire Series Related Content AIDSource | Vaccine Research HIV Vaccines History of HIV Vaccine Research Need Help? Call 1- ... Entire Series Related Content AIDSource | Vaccine Research HIV Vaccines History of HIV Vaccine Research Need Help? Call 1- ...
Jesani, Amar; Johari, Veena
Vaccines and vaccination have emerged as key medical scientific tools for prevention of certain diseases. Documentation of the history of vaccination shows that the initial popular resistance to universal vaccination was based on false assumptions and eventually gave way to acceptance of vaccines and trust in their ability to save lives. The successes of the global eradication of smallpox, and now of polio, have only strengthened the premier position occupied by vaccines in disease prevention. However, the success of vaccines and public trust in their ability to eradicate disease are now under challenge, as increasing numbers of people refuse vaccination, questioning the effectiveness of vaccines and the need to vaccinate.
Wang, Jen-Ren; Chi, Chia-Yu; Chong, Pele; Su, Ih-Jen
Human enteroviruses usually cause self-limited infections except polioviruses and enterovirus 71 (EV71), which frequently involve neurological complications. EV71 vaccines are being evaluated in humans. However, several challenges to licensure of EV71 vaccines need to be addressed. Firstly, EV71 and coxsackievirus A (CA) are frequently found to co-circulate and cause hand-foot-mouth disease (HFMD). A polyvalent vaccine that can provide protection against EV71 and prevalent CA are desirable. Secondly, infants are the target population of HFMD vaccines and it would need multi-national efficacy trials to prove clinical protection and speed up the licensure and usage of HFMD vaccines in children. An international network for enterovirus surveillance and clinical trials is urgently needed. Thirdly, EV71 is found to evolve quickly in the past 15 years. Prospective cohort studies are warranted to clarify clinical and epidemiological significances of the antigenic and genetic variations between different EV71 genogroups, which is critical for vaccine design. PMID:22953003
Full Text Available Human enteroviruses usually cause self-limited infections except polioviruses and enterovirus 71 (EV71, which frequently involve neurological complications. EV71 vaccines are being evaluated in humans. However, several challenges to licensure of EV71 vaccines need to be addressed. Firstly, EV71 and coxsackievirus A (CA are frequently found to co-circulate and cause hand-foot-mouth disease (HFMD. A polyvalent vaccine that can provide protection against EV71 and prevalent CA are desirable. Secondly, infants are the target population of HFMD vaccines and it would need multi-national efficacy trials to prove clinical protection and speed up the licensure and usage of HFMD vaccines in children. An international network for enterovirus surveillance and clinical trials is urgently needed. Thirdly, EV71 is found to evolve quickly in the past 15 years. Prospective cohort studies are warranted to clarify clinical and epidemiological significances of the antigenic and genetic variations between different EV71 genogroups, which is critical for vaccine design.
Full Text Available Development of novel vaccine deliveries and vaccine adjuvants is of great importance to address the dilemma that the vaccine field faces: to improve vaccine efficacy without compromising safety. Harnessing the specific effects of laser on biological systems, a number of novel concepts have been proposed and proved in recent years to facilitate vaccination in a safer and more efficient way. The key advantage of using laser technology in vaccine delivery and adjuvantation is that all processes are initiated by physical effects with no foreign chemicals administered into the body. Here, we review the recent advances in using laser technology to facilitate vaccine delivery and augment vaccine efficacy as well as the underlying mechanisms.
The Vaccine Safety Datalink is part of the National Immunization Program within the Centers for Disease Control and Prevention and was started in recognition of gaps in the scientific knowledge of rare vaccine side effects.
Following the release of a consensus statement from the NCI-Designated Cancer Centers urging HPV vaccination in the United States, Dr. Noel Brewer discusses the country’s low vaccination rates and how clinicians can help to improve them.
... term seizures, coma, lowered consciousness, and permanent brain damage have been reported following DTaP vaccination. These reports are extremely rare. Pneumococcal Vaccine Mild Problems: drowsiness or temporary loss of appetite ( ...
... term seizures, coma, lowered consciousness, and permanent brain damage have been reported following DTaP vaccination. These reports are extremely rare. Pneumococcal Vaccine Mild Problems: Drowsiness or temporary loss of appetite ( ...
Williamson, Eric M L; Chahin, Salim; Berger, Joseph R
Vaccinations help prevent communicable disease. To be valuable, a vaccine's ability to prevent disease must exceed the risk of adverse effects from administration. Many vaccines present no risk of infection as they are comprised of killed or non-infectious components while other vaccines consist of live attenuated microorganisms which carry a potential risk of infection-particularly, in patients with compromised immunity. There are several unique considerations with respect to vaccination in the multiple sclerosis (MS) population. First, there has been concern that vaccination may trigger or aggravate the disease. Second, disease-modifying therapies (DMTs) employed in the treatment of MS may increase the risk of infectious complications from vaccines or alter their efficacy. Lastly, in some cases, vaccination strategies may be part of the treatment paradigm in attempts to avoid complications of therapy.
vaccines for malaria and HIV infection. Despite the ... decades, effective vaccines against the major causes of ... challenge antibodies, specific helper and effector T lymphocytes ... materials to produced immunity to a disease. It was originally ...
... Educators Search English Español Your Child's Immunizations: Pneumococcal Vaccines (PCV, PPSV) KidsHealth / For Parents / Your Child's Immunizations: ... cochlear implants. Why Are the PCV and PPSV Vaccines Recommended? Children younger than 2 years old, adults ...
New strategies to genetically manipulate the genomes of several important animal pathogens have been established in recent years. This article focuses on the reverse genetics techniques, which enables genetic manipulation of the genomes of non-segmented negative-sense RNA viruses. Recovery of a negative-sense RNA virus entirely from cDNA was first achieved for rabies virus in 1994. Since then, reverse genetic systems have been established for several pathogens of medical and veterinary importance. Based on the reverse genetics technique, it is now possible to design safe and more effective live attenuated vaccines against important viral agents. In addition, genetically tagged recombinant viruses can be designed to facilitate serological differentiation of vaccinated animals from infected animals. The approach of delivering protective immunogens of different pathogens using a single vector was made possible with the introduction of the reverse genetics system, and these novel broad-spectrum vaccine vectors have potential applications in improving animal health in developing countries. (author)
Otrashevskaia, E V; Kulak, M V; Otrashevskaia, A V; Karpov, I A; Fisenko, E G; Ignat'ev, G M
In this work we report the mumps vaccine virus shedding based on the laboratory confirmed cases of the mumps virus (MuV) infection. The likely epidemiological sources of the transmitted mumps virus were children who were recently vaccinated with the mumps vaccine containing Leningrad-Zagreb or Leningrad-3 MuV. The etiology of the described cases of the horizontal transmission of both mumps vaccine viruses was confirmed by PCR with the sequential restriction analysis.
Midthun, K; Kapikian, A Z
Rotavirus vaccine development has focused on the delivery of live attenuated rotavirus strains by the oral route. The initial "Jennerian" approach involving bovine (RIT4237, WC3) or rhesus (RRV) rotavirus vaccine candidates showed that these vaccines were safe, well tolerated, and immunogenic but induced highly variable rates of protection against rotavirus diarrhea. The goal of a rotavirus vaccine is to prevent severe illness that can lead to dehydration in infants and young children in both...
S. M. Kharit
Full Text Available Massive vaccination had proved its effective morbidity reduction. Today it is necessary to extend vaccination schedule, creation of selective, regional schedules based on epidemiological, clinical, economical substantiation. Development of vaccination needs the profound scientific research, modernization of adverse reaction observing system, betterment training system and awareness of population.
Embregts, Carmen W.E.; Forlenza, Maria
The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen
... previous dose of meningococcal vaccine, to the DTaP vaccine , or to latex If your child has a history of Guillain-Barré syndrome (a disease of the nervous system that causes progressive weakness), talk to your doctor about whether the vaccines are a good idea. Caring for Your Child ...
Twinrix® (as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... Why get vaccinated against hepatitis A?Hepatitis A is a serious liver disease. It is caused by the hepatitis A virus (HAV). HAV is spread from ...
Flipse, Jacky; Smit, Jolanda M.
Dengue is the most prevalent mosquito-borne viral disease worldwide. Yet, there are no vaccines or specific antivirals available to prevent or treat the disease. Several dengue vaccines are currently in clinical or preclinical stages. The most advanced vaccine is the chimeric tetravalent CYD-TDV vaccine of Sanofi Pasteur. This vaccine has recently cleared Phase III, and efficacy results have been published. Excellent tetravalent seroconversion was seen, yet the protective efficacy against infection was surprisingly low. Here, we will describe the complicating factors involved in the generation of a safe and efficacious dengue vaccine. Furthermore, we will discuss the human antibody responses during infection, including the epitopes targeted in humans. Also, we will discuss the current understanding of the assays used to evaluate antibody response. We hope this review will aid future dengue vaccine development as well as fundamental research related to the phenomenon of antibody-dependent enhancement of dengue virus infection. PMID:26065421
Full Text Available Dengue is the most prevalent mosquito-borne viral disease worldwide. Yet, there are no vaccines or specific antivirals available to prevent or treat the disease. Several dengue vaccines are currently in clinical or preclinical stages. The most advanced vaccine is the chimeric tetravalent CYD-TDV vaccine of Sanofi Pasteur. This vaccine has recently cleared Phase III, and efficacy results have been published. Excellent tetravalent seroconversion was seen, yet the protective efficacy against infection was surprisingly low. Here, we will describe the complicating factors involved in the generation of a safe and efficacious dengue vaccine. Furthermore, we will discuss the human antibody responses during infection, including the epitopes targeted in humans. Also, we will discuss the current understanding of the assays used to evaluate antibody response. We hope this review will aid future dengue vaccine development as well as fundamental research related to the phenomenon of antibody-dependent enhancement of dengue virus infection.
Curran, James R.
As early as the 1930s the term Master Hearing Aid (MHA) described a device used in the fitting of hearing aids. In their original form, the MHA was a desktop system that allowed for simulated or actual adjustment of hearing aid components that resulted in a changed hearing aid response. Over the years the MHA saw many embodiments and contributed to a number of rationales for the fitting of hearing aids. During these same years, the MHA was viewed by many as an inappropriate means of demonstrating hearing aids; the audio quality of the desktop systems was often superior to the hearing aids themselves. These opinions and the evolution of the MHA have molded the modern perception of hearing aids and the techniques used in the fitting of hearing aids. This article reports on a history of the MHA and its influence on the fitting of hearing aids. PMID:23686682
Rappuoli, Rino; Hanon, Emmanuel
Vaccination remains the most cost-effective public health intervention after clean water, and the benefits impressively outweigh the costs. The efforts needed to fulfill the steadily growing demands for next-generation and novel vaccines designed for emerging pathogens and new indications are only realizable in a sustainable business model. Vaccine development can be fast-tracked through strengthening international collaborations, and the continuous innovation of technologies to accelerate their design, development, and manufacturing. However, these processes should be supported by a balanced project portfolio, and by managing sustainable vaccine procurement strategies for different types of markets. Collectively this will allow a gradual shift to a more streamlined and profitable vaccine production, which can significantly contribute to the worldwide effort to shape global health. Copyright © 2018 GlaxoSmithKine Biologicals SA. Published by Elsevier Ltd.. All rights reserved.
Billeskov, Rolf; Lindenstrøm, Thomas; Woodworth, Joshua; Vilaplana, Cristina; Cardona, Pere-Joan; Cassidy, Joseph P; Mortensen, Rasmus; Agger, Else Marie; Andersen, Peter
Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), causes 1.8M deaths annually. The current vaccine, BCG, has failed to eradicate TB leaving 25% of the world's population with latent Mtb infection (LTBI), and 5-10% of these people will reactivate and develop active TB. An efficient therapeutic vaccine targeting LTBI could have an enormous impact on global TB incidence, and could be an important aid in fighting multidrug resistance, which is increasing globally. Here we show in a mouse model using the H56 (Ag85B-ESAT-6-Rv2660) TB vaccine candidate that post-exposure, but not preventive, vaccine protection requires low vaccine antigen doses for optimal protection. Loss of protection from high dose post-exposure vaccination was not associated with a loss of overall vaccine response magnitude, but rather with greater differentiation and lower functional avidity of vaccine-specific CD4 T cells. High vaccine antigen dose also led to a decreased ability of vaccine-specific CD4 T cells to home into the Mtb-infected lung parenchyma, a recently discovered important feature of T cell protection in mice. These results underscore the importance of T cell quality rather than magnitude in TB-vaccine protection, and the significant role that antigen dosing plays in vaccine-mediated protection.
Full Text Available Mycobacterium tuberculosis (Mtb, the etiologic agent of tuberculosis (TB, causes 1.8M deaths annually. The current vaccine, BCG, has failed to eradicate TB leaving 25% of the world’s population with latent Mtb infection (LTBI, and 5–10% of these people will reactivate and develop active TB. An efficient therapeutic vaccine targeting LTBI could have an enormous impact on global TB incidence, and could be an important aid in fighting multidrug resistance, which is increasing globally. Here we show in a mouse model using the H56 (Ag85B-ESAT-6-Rv2660 TB vaccine candidate that post-exposure, but not preventive, vaccine protection requires low vaccine antigen doses for optimal protection. Loss of protection from high dose post-exposure vaccination was not associated with a loss of overall vaccine response magnitude, but rather with greater differentiation and lower functional avidity of vaccine-specific CD4 T cells. High vaccine antigen dose also led to a decreased ability of vaccine-specific CD4 T cells to home into the Mtb-infected lung parenchyma, a recently discovered important feature of T cell protection in mice. These results underscore the importance of T cell quality rather than magnitude in TB-vaccine protection, and the significant role that antigen dosing plays in vaccine-mediated protection.
Hatziioannou, Theodora; Evans, David T.
The AIDS pandemic continues to present us with unique scientific and public health challenges. Although the development of effective antiretroviral therapy has been a major triumph, the emergence of drug resistance requires active management of treatment regimens and the continued development of new antiretroviral drugs. Moreover, despite nearly 30 years of intensive investigation, we still lack the basic scientific knowledge necessary to produce a safe and effective vaccine against HIV-1. Animal models offer obvious advantages in the study of HIV/AIDS, allowing for a more invasive investigation of the disease and for preclinical testing of drugs and vaccines. Advances in humanized mouse models, non-human primate immunogenetics and recombinant challenge viruses have greatly increased the number and sophistication of available mouse and simian models. Understanding the advantages and limitations of each of these models is essential for the design of animal studies to guide the development of vaccines and antiretroviral therapies for the prevention and treatment of HIV-1 infection. PMID:23154262
Rory C. F. De Brito
Full Text Available Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.
De Brito, Rory C F; Cardoso, Jamille M De O; Reis, Levi E S; Vieira, Joao F; Mathias, Fernando A S; Roatt, Bruno M; Aguiar-Soares, Rodrigo Dian D O; Ruiz, Jeronimo C; Resende, Daniela de M; Reis, Alexandre B
Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.
Lemaire, D.; Barbosa, T.; Rihet, P.
Vaccine development faces major difficulties partly because of genetic variation in both infectious organisms and humans. This causes antigenic variation in infectious agents and a high interindividual variability in the human response to the vaccine. The exponential growth of genome sequence information has induced a shift from conventional culture-based to genome-based vaccinology, and allows the tackling of challenges in vaccine development due to pathogen genetic variability. Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. Accumulating results provide evidence for the existence of a number of genes involved in protective immune responses that are induced either by natural infections or vaccines. Variation in immune responses could be viewed as the result of a perturbation of gene networks; this should help in understanding how a particular polymorphism or a combination thereof could affect protective immune responses. Here we will present: i) the first genome-based vaccines that served as proof of concept, and that provided new critical insights into vaccine development strategies; ii) an overview of genetic predisposition in infectious diseases and genetic control in responses to vaccines; iii) population genetic differences that are a rationale behind group-targeted vaccines; iv) an outlook for genetic control in infectious diseases, with special emphasis on the concept of molecular networks that will provide a structure to the huge amount of genomic data
Sopracordevole, F; Cigolot, F; Gardonio, V; Di Giuseppe, J; Boselli, F; Ciavattini, A
The aim of this study was to assess teens' knowledge of HPV infection and vaccination one year after the initiation of the public vaccination programme and information campaign on the disease and the opportunity of vaccination. Between 15 May and 15 June 2009, a survey was carried out on 1,105 teenagers attending high schools in a town in the northeast of Italy by means of an anonymous and unannounced questionnaire covering the knowledge of HPV infection, transmission, prevention, vaccination and post-vaccination behaviours. Only 75% of teens knew what HPV infection is (92% of girls vs 51% of boys, p teens aware of HPV vaccination, 7.6% of girls and 21.8% of boys believe that it can prevent AIDS (p Teens' knowledge about HPV infection and vaccination remains insufficient, despite a broad information campaign. Erroneous information may increase risky sexual behaviours. Without complete information about HPV infection and vaccination and information about other sexually-transmitted diseases, the latter might become difficult to control among teenagers, while some misunderstandings about the usefulness of secondary prevention might linger.
Jacob D. Galson
Full Text Available Generating a diverse B cell immunoglobulin repertoire is essential for protection against infection. The repertoire in humans can now be comprehensively measured by high-throughput sequencing. Using hepatitis B vaccination as a model, we determined how the total immunoglobulin sequence repertoire changes following antigen exposure in humans, and compared this to sequences from vaccine-specific sorted cells. Clonal sequence expansions were seen 7 days after vaccination, which correlated with vaccine-specific plasma cell numbers. These expansions caused an increase in mutation, and a decrease in diversity and complementarity-determining region 3 sequence length in the repertoire. We also saw an increase in sequence convergence between participants 14 and 21 days after vaccination, coinciding with an increase of vaccine-specific memory cells. These features allowed development of a model for in silico enrichment of vaccine-specific sequences from the total repertoire. Identifying antigen-specific sequences from total repertoire data could aid our understanding B cell driven immunity, and be used for disease diagnostics and vaccine evaluation.
Galson, Jacob D; Trück, Johannes; Fowler, Anna; Clutterbuck, Elizabeth A; Münz, Márton; Cerundolo, Vincenzo; Reinhard, Claudia; van der Most, Robbert; Pollard, Andrew J; Lunter, Gerton; Kelly, Dominic F
Generating a diverse B cell immunoglobulin repertoire is essential for protection against infection. The repertoire in humans can now be comprehensively measured by high-throughput sequencing. Using hepatitis B vaccination as a model, we determined how the total immunoglobulin sequence repertoire changes following antigen exposure in humans, and compared this to sequences from vaccine-specific sorted cells. Clonal sequence expansions were seen 7 days after vaccination, which correlated with vaccine-specific plasma cell numbers. These expansions caused an increase in mutation, and a decrease in diversity and complementarity-determining region 3 sequence length in the repertoire. We also saw an increase in sequence convergence between participants 14 and 21 days after vaccination, coinciding with an increase of vaccine-specific memory cells. These features allowed development of a model for in silico enrichment of vaccine-specific sequences from the total repertoire. Identifying antigen-specific sequences from total repertoire data could aid our understanding B cell driven immunity, and be used for disease diagnostics and vaccine evaluation.
Pauly, Mark V
This paper explores the relationship between the research for and development of vaccines against global pandemics and insurance. It shows that development in advance of pandemics of a portfolio of effective and government-approved vaccines does have some insurance properties: it requires incurring costs that are certain (the costs of discovering, developing, and testing vaccines) in return for protection against large losses (if a pandemic treatable with one of the vaccines occurs) but also with the possibility of no benefit (from a vaccine against a disease that never reaches the pandemic stage). It then argues that insurance against the latter event might usefully be offered to organizations developing vaccines, and explores the benefits of insurance payments to or on behalf of countries who suffer from unpredictable pandemics. These ideas are then related to recent government, industry, and philanthropic efforts to develop better policies to make vaccines against pandemics available on a timely basis.
Mark V. Pauly
Full Text Available This paper explores the relationship between the research for and development of vaccines against global pandemics and insurance. It shows that development in advance of pandemics of a portfolio of effective and government-approved vaccines does have some insurance properties: it requires incurring costs that are certain (the costs of discovering, developing, and testing vaccines in return for protection against large losses (if a pandemic treatable with one of the vaccines occurs but also with the possibility of no benefit (from a vaccine against a disease that never reaches the pandemic stage. It then argues that insurance against the latter event might usefully be offered to organizations developing vaccines, and explores the benefits of insurance payments to or on behalf of countries who suffer from unpredictable pandemics. These ideas are then related to recent government, industry, and philanthropic efforts to develop better policies to make vaccines against pandemics available on a timely basis.
Zhang, Min; Hu, Yong-Hua; Xiao, Zhi-Zhong; Sun, Yun; Sun, Li
Iridoviruses are large double-stranded DNA viruses with icosahedral capsid. The Iridoviridae family contains five genera, one of which is Megalocytivirus. Megalocytivirus has emerged in recent years as an important pathogen to a wide range of marine and freshwater fish. In this study, we aimed at developing effective genetic vaccines against megalocytivirus affecting farmed fish in China. For this purpose, we constructed seven DNA vaccines based on seven genes of rock bream iridovirus isolate 1 from China (RBIV-C1), a megalocytivirus with a host range that includes Japanese flounder (Paralichthys olivaceus) and turbot (Scophthalmus maximus). The protective potentials of these vaccines were examined in a turbot model. The results showed that after vaccination via intramuscular injection, the vaccine plasmids were distributed in spleen, kidney, muscle, and liver, and transcription of the vaccine genes and production of the vaccine proteins were detected in these tissues. Following challenge with a lethal-dose of RBIV-C1, fish vaccinated with four of the seven DNA vaccines exhibited significantly higher levels of survival compared to control fish. Of these four protective DNA vaccines, pCN86, which is a plasmid that expresses an 86-residue viral protein, induced the highest protection. Immunological analysis showed that pCN86 was able to (i) stimulate the respiratory burst of head kidney macrophages at 14 d, 21 d, and 28 d post-vaccination, (ii) upregulate the expression of immune relevant genes involved in innate and adaptive immunity, and (iii) induce production of serum antibodies that, when incubated with RBIV-C1 before infection, significantly reduced viral loads in kidney and spleen following viral infection of turbot. Taken together, these results indicate that pCN86 is an effective DNA vaccine that may be used in the control of megalocytivirus-associated diseases in aquaculture. Copyright © 2012 Elsevier Ltd. All rights reserved.
... 42 Public Health 2 2010-10-01 2010-10-01 false Pneumococcal vaccine and flu vaccine. 410.57 Section 410.57 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its...
mash feed as vaccine carriers was conducted. Newcastle disease vaccine strain I2 and. NDV La Sota vaccines provided protection to commercial and local chickens vaccinated through i/o, i/m or dw. No significant difference (P≤0.05) was observed in the antibody titre of commercial or local chickens vaccinated with either ...
Full Text Available BACKGROUND: The objective of the study was to analyse the evolution of Bordetella pertussis population and the influence of herd immunity in different areas of the world where newborns and infants are highly vaccinated. METHODOLOGY: The analysis was performed using DNA microarray on 15 isolates, PCR on 111 isolates as well as GS-FLX sequencing technology on 3 isolates and the B. pertussis reference strain, Tohama I. PRINCIPAL FINDINGS: Our analyses demonstrate that the current circulating isolates are continuing to lose genetic material as compared to isolates circulating during the pre-vaccine era whatever the area of the world considered. The lost genetic material does not seem to be important for virulence. Our study confirms that the use of whole cell vaccines has led to the control of isolates that were similar to vaccine strains. GS-FLX sequencing technology shows that current isolates did not acquire any additional material when compared with vaccine strains or with isolates of the pre-vaccine era and that the sequenced strain Tohama I is not representative of the isolates. Furthermore, this technology allowed us to observe that the number of Insertion Sequence elements contained in the genome of the isolates is temporally increasing or varying between isolates. CONCLUSIONS: B. pertussis adaptation to humans is still in progress by losing genetic material via Insertion Sequence elements. Furthermore, recent isolates did not acquire any additional material when compared with vaccine strains or with isolates of the pre-vaccine era. Herd immunity, following intensive vaccination of infants and children with whole cell vaccines, has controlled isolates similar to the vaccine strains without modifying significantly the virulence of the isolates. With the replacement of whole cell vaccines by subunit vaccines, containing only few bacterial antigens targeting the virulence of the bacterium, one could hypothesize the circulation of isolates
Kumar, Arun; Meldgaard, Trine Sundebo; Bertholet, Sylvie
Despite advancements in immunotherapeutic approaches, influenza continues to cause severe illness, particularly among immunocompromised individuals, young children, and elderly adults. Vaccination is the most effective way to reduce rates of morbidity and mortality caused by influenza viruses....... Frequent genetic shift and drift among influenzavirus strains with the resultant disparity between circulating and vaccine virus strains limits the effectiveness of the available conventional influenza vaccines. One approach to overcome this limitation is to develop a universal influenza vaccine that could...... provide protection against all subtypes of influenza viruses. Moreover, the development of a novel or improved universal influenza vaccines may be greatly facilitated by new technologies including virus-like particles, T-cell-inducing peptides and recombinant proteins, synthetic viruses, broadly...
Munang'andu, Hetron M; Fredriksen, Børge N; Mutoloki, Stephen; Brudeseth, Bjørn; Kuo, Tsun-Yung; Marjara, Inderjit S; Dalmo, Roy A; Evensen, Øystein
Two strains of IPNV made by reverse genetics on the Norwegian Sp strain NVI-015 (GenBank AY379740) backbone encoding the virulent (T(217)A(221)) and avirulent (P(217)T(221)) motifs were used to prepare inactivated whole virus (IWV), nanoparticle vaccines with whole virus, Escherichia coli subunit encoding truncated VP2-TA and VP2-PT, VP2-TA and VP2-PT fusion antigens with putative translocating domains of Pseudomonas aeruginosa exotoxin, and plasmid DNA encoding segment A of the TA strain. Post challenge survival percentages (PCSP) showed that IWV vaccines conferred highest protection (PCSP=42-53) while nanoparticle, sub-unit recombinant and DNA vaccines fell short of the IWV vaccines in Atlantic salmon (Salmo salar L.) postsmolts challenged with the highly virulent Sp strain NVI-015 (TA strain) of IPNV after 560 degree days post vaccination. Antibody levels induced by these vaccines did not show antigenic differences between the virulent and avirulent motifs for vaccines made with the same antigen dose and delivery system after 8 weeks post vaccination. Our findings show that fish vaccinated with less potent vaccines comprising of nanoparticle, DNA and recombinant vaccines got infected much earlier and yielded to higher infection rates than fish vaccinated with IWV vaccines that were highly potent. Ability of the virulent (T(217)A(221)) and avirulent (P(217)T(221)) motifs to limit establishment of infection showed equal protection for vaccines made of the same antigen dose and delivery systems. Prevention of tissue damage linked to viral infection was eminent in the more potent vaccines than the less protective ones. Hence, there still remains the challenge of developing highly efficacious vaccines with the ability to eliminate the post challenge carrier state in IPNV vaccinology. Copyright © 2012 Elsevier Ltd. All rights reserved.
AIDS epidemic in terms of infection rates, vulnerability and impact, with the Joint .... 17-year-old, HIV-negative male and female adolescents. Sites at five ..... the HPV vaccine was framed in this study as a means to prevent STI, rather than the more ... thank Merck Sharp & Dohme (MSD) for their generous donation of. Gardasil ...
HIV/AIDS Vaccines Ethics Group (HAVEG), School of Psychology, University of. KwaZulu-Natal ... receive access to risk reduction counselling on safer sex, education .... debate regarding how to proceed should acyclovir have shown to decrease HIV ... or a single pivotal trial (phase III trial) that provides as much evidence of ...
Wang, Chia-ching J.; Sparano, Joseph; Palefsky, Joel M.
SYNOPSIS Anal cancer is an increasingly common non-AIDS-defining cancer among HIV-infected individuals. It is associated with human papillomavirus (HPV), the most common sexually transmitted infectious agent. The 14 oncogenic types of HPV are causally associated with 5–10% of all cancers, notably anogenital cancers. HPV16 is the most common genotype detected in about 70% of anal cancers. The HPV types detected in anal cancer are included in the 9-valent vaccine. HPV vaccines have demonstrated efficacy in reducing anal precancerous lesions in HIV-infected individuals. The standard treatment for anal cancer has been fluorouracil (5-FU) and mitomycin (or cisplatin) as chemotherapy agents plus radiation, which can also be effectively used for the HIV-infected patients. Continued studies will be needed to test new treatment strategies in HIV-infected patients with anal cancer to determine which treatment protocols provide the best therapeutic index. PMID:27889034
Full Text Available Rheumatoid arthritis (RA is the most common chronic inflammatory joint disease. Multiple scientific articles have documented that vaccinations for influenza, MMR, and HBV, to name a few, could be triggers of RA in genetically predisposed individuals. However, there is limited data regarding the association of swine flu vaccine (H1N1 and RA. We report the case of a Mexican American female who developed RA right after vaccination with H1N1 vaccine. Genetically, RA has consistently been associated with an epitope in the third hypervariable region of the HLA-DR chains, known as the “shared epitope”, which is found primarily in DR4 and DR1 regions. The presence of HLA-DRB1 alleles is associated with susceptibility to RA in Mexican Americans. Hence, certain individuals with the presence of the “shared epitope” may develop RA following specific vaccinations. To our knowledge, this is the first reported case of RA following vaccination with the swine flu vaccine.
The June 1989 International Conference on AIDS in Montreal had a record attendance of 11,000 including several thousand journalists, representatives of pharmaceutical companies, sociologists, psychologists, and numerous AIDS patients primarily from the US. The opening session was postponed for several hours by demonstrators protesting the government response to AIDS. The initial plenary sessions failed to present information on scientific progress against AIDS but focused on topics such as tolerance, the faults of humanity, and the difficult life of homosexuals. The 6000 communications presented a pessimistic picture of the prospects for controlling the epidemic, especially in Africa. Several studies indicated that condom use is very limited in Africa and that no national policy has succeeded in reducing the rate of new infections. The few notes of hope concerned the improved management of AIDS cases in the industrialized countries, which have increased 18-month survival rates from 30% in 1982 to 60% in 1988. The difficulty and expense of treatments however mean that they are unlikely to be adopted in countries with limited health resources. Vaccines under development in France and the US show promise, but there is little hope of a cure in the near future. AZT is believed to improve the quality of survival time rather than the duration. Some new antivirals under study are too highly toxic for practical use.
Ravel, G.; Christ, M.; Horand, F.; Descotes, J.
Although the wide clinical experience shows that vaccines are generally safe, concern has been expressed for a causal link between vaccines and autoimmune diseases. Even though the mechanisms of autoimmunity are ill-elucidated, the role of pre-existing risk factors including genetic predisposition and environmental factors is largely accepted. The present study was undertaken to test the hypothesis that vaccines can promote autoimmunity in genetically-prone individuals when simultaneously exposed to a chemical known to induce autoimmune reactions. Female lupus-prone (NZBxNZW) F 1 mice were given 1 μg or 10 μg of a hepatitis B vaccine at 2-week intervals in conjunction with 40 μg of mercuric chloride three times per week for 6 weeks. A marked increase in serum IgG levels and a slight increase in anti-nuclear autoantibody (ANA) levels were seen in the mice given 10 μg of the vaccine plus mercuric chloride. No straightforward conclusion can be drawn from these results because of the extreme experimental conditions of this study. Nevertheless, the results tend to support the hypothesis that vaccination could enhance the risk of autoimmunity in genetically susceptible individuals when exposed to certain environmental chemicals
Full Text Available Bacterial artificial chromosome (BAC clones have proven invaluable for genetic manipulation of herpesvirus genomes. BAC cloning can also be useful for capturing representative genomes that comprise a viral stock or mixture. The Towne live attenuated cytomegalovirus vaccine was developed in the 1970s by serial passage in cultured fibroblasts. Although its safety, immunogenicity, and efficacy have been evaluated in nearly a thousand human subjects, the vaccine itself has been little studied. Instead, genetic composition and in vitro growth properties have been inferred from studies of laboratory stocks that may not always accurately represent the viruses that comprise the vaccine. Here we describe the use of BAC cloning to define the genotypic and phenotypic properties of viruses from the Towne vaccine. Given the extensive safety history of the Towne vaccine, these BACs provide a logical starting point for the development of next-generation rationally engineered cytomegalovirus vaccines.
Cui, Xiaohong; Adler, Stuart P; Davison, Andrew J; Smith, Larry; Habib, El-Sayed E; McVoy, Michael A
Bacterial artificial chromosome (BAC) clones have proven invaluable for genetic manipulation of herpesvirus genomes. BAC cloning can also be useful for capturing representative genomes that comprise a viral stock or mixture. The Towne live attenuated cytomegalovirus vaccine was developed in the 1970s by serial passage in cultured fibroblasts. Although its safety, immunogenicity, and efficacy have been evaluated in nearly a thousand human subjects, the vaccine itself has been little studied. Instead, genetic composition and in vitro growth properties have been inferred from studies of laboratory stocks that may not always accurately represent the viruses that comprise the vaccine. Here we describe the use of BAC cloning to define the genotypic and phenotypic properties of viruses from the Towne vaccine. Given the extensive safety history of the Towne vaccine, these BACs provide a logical starting point for the development of next-generation rationally engineered cytomegalovirus vaccines.
Hoenen, Thomas; Groseth, Allison; Feldmann, Heinz
Introduction Ebolaviruses cause severe viral hemorrhagic fever in humans and non-human primates, with case fatality rates of up to 90%. Currently, neither a specific treatment nor a vaccine licensed for use in humans is available. However, a number of vaccine candidates have been developed in the last decade that are highly protective in non-human primates, the gold standard animal model for Ebola hemorrhagic fever. Areas covered This review analyzes a number of scenarios for the use of ebolavirus vaccines, discusses the requirements for ebolavirus vaccines in these scenarios, and describes current ebolavirus vaccines. Among these vaccines are recombinant Adenoviruses, recombinant Vesicular Stomatitis viruses, recombinant Human Parainfluenza viruses and virus-like particles. Interestingly, one of these vaccine platforms, based on recombinant Vesicular Stomatitis viruses, has also demonstrated post-exposure protection in non-human primates. Expert opinion The most pressing remaining challenge is now to move these vaccine candidates forward into human trials and towards licensure. In order to achieve this, it will be necessary to establish the mechanisms and correlates of protection for these vaccines, and to continue to demonstrate their safety, particularly in potentially immunocompromised populations. However, already now there is sufficient evidence that, from a scientific perspective, a vaccine protective against ebolaviruses is possible. PMID:22559078
Søborg, Christian; Mølbak, Kåre; Doherty, T Mark; Ulleryd, Peter; Brooks, Tim; Coenen, Claudine; van der Zeijst, Ben
Preparing populations for health threats, including threats from new or re-emerging infectious diseases is recognised as an important public health priority. The development, production and application of emergency vaccinations are the important measures against such threats. Vaccines are cost-effective tools to prevent disease, and emergency vaccines may be the only means to prevent a true disaster for global society in the event of a new pandemic with potential to cause morbidity and mortality comparable to the Spanish flu, the polio epidemics in the 1950s, or the SARS outbreak in 2003 if its spread had not been contained in time. Given the early recognition of a new threat, and given the advances of biotechnology, vaccinology and information systems, it is not an unrealistic goal to have promising prototype vaccine candidates available in a short time span following the identification of a new infectious agent; this is based on the assumption that the emerging infection is followed by natural immunity. However, major bottlenecks for the deployment of emergency vaccine are lack of established systems for fast-track regulatory approval of such candidates and limited international vaccine production capacity. In the present discussion paper, we propose mechanisms to facilitate development of emergency vaccines in Europe by focusing on public-private scientific partnerships, fast-track approval of emergency vaccine by regulatory agencies and proposing incentives for emergency vaccine production in private vaccine companies.
Development of a combined canine distemper virus specific RT-PCR protocol for the differentiation of infected and vaccinated animals (DIVA) and genetic characterization of the hemagglutinin gene of seven Chinese strains demonstrated in dogs.
Yi, Li; Cheng, Shipeng; Xu, Hongli; Wang, Jianke; Cheng, Yuening; Yang, Shen; Luo, Bin
A combined reverse-transcription polymerase chain reaction (RT-PCR) method was developed for the detection and differentiation of wild-type and vaccine strains of the canine distemper virus (CDV). A pair of primers (P1/P2) was used to detect both CDV wild-type strains and vaccines. Another pair (P3/P4) was used to detect only CDV wild-type strains. A 335bp fragment was amplified from the genomic RNA of the vaccine and wild-type strains. A 555bp fragment was amplified specifically from the genomic RNA of the wild-type strains. No amplification was achieved for the uninfected cells, cells infected with canine parvovirus, canine coronavirus, or canine adenovirus. The combined RT-PCR method detected effectively and differentiated the CDV wild-type and vaccine strains by two separate RT-PCRs. The method can be used for clinical detection and epidemiological surveillance. The phylogenetic analysis of the hemagglutinin gene of the local wild-type CDV strains revealed that the seven local isolates all belonged to the Asia-1 lineage, and were clustered closely with one another at the same location. These results suggested that the CDV genotype Asia-1 is circulating currently in domestic dogs in China. Copyright © 2011 Elsevier B.V. All rights reserved.
Hardt, Karin; Bonanni, Paolo; King, Susan; Santos, Jose Ignacio; El-Hodhod, Mostafa; Zimet, Gregory D; Preiss, Scott
Successful immunisation programmes generally result from high vaccine effectiveness and adequate uptake of vaccines. In the development of new vaccination strategies, the structure and strength of the local healthcare system is a key consideration. In high income countries, existing infrastructures are usually used, while in less developed countries, the capacity for introducing new vaccines may need to be strengthened, particularly for vaccines administered beyond early childhood, such as the measles or human papillomavirus (HPV) vaccine. Reliable immunisation service funding is another important factor and low income countries often need external supplementary sources of finance. Many regions also obtain support in generating an evidence base for vaccination via initiatives created by organisations including World Health Organization (WHO), the Pan American Health Organization (PAHO), the Agence de Médecine Préventive and the Sabin Vaccine Institute. Strong monitoring and surveillance mechanisms are also required. An example is the efficient and low-cost approaches for measuring the impact of the hepatitis B control initiative and evaluating achievement of goals that have been established in the WHO Western Pacific region. A review of implementation strategies reveals differing degrees of success. For example, in the Americas, PAHO advanced a measles-mumps-rubella vaccine strategy, targeting different population groups in mass, catch-up and follow-up vaccination campaigns. This has had much success but coverage data from some parts of the region suggest that children are still not receiving all appropriate vaccines, highlighting problems with local service infrastructures. Stark differences in coverage levels are also observed among high income countries, as is the case with HPV vaccine implementation in the USA versus the UK and Australia, reflecting differences in delivery settings. Experience and research have shown which vaccine strategies work well and the
LaForce, F Marc; Konde, Kader; Viviani, Simonetta; Préziosi, Marie-Pierre
Epidemic meningococcal meningitis is an important public health problem in sub-Saharan Africa. Current control measures rely on reactive immunizations with polysaccharide (PS) vaccines that do not induce herd immunity and are of limited effectiveness in those under 2 years of age. Conversely, polysaccharide conjugate vaccines are effective in infants and have consistently shown an important effect on decreasing carriage, two characteristics that facilitate disease control. In 2001 the Meningitis Vaccine Project (MVP) was created as a partnership between PATH and the World Health Organization (WHO) with the goal of eliminating meningococcal epidemics in Africa through the development, licensure, introduction, and widespread use of conjugate meningococcal vaccines. Since group A Neisseria meningitidis (N. meningitidis) is the dominant pathogen causing epidemic meningitis in Africa MVP is developing an affordable (US$ 0.40 per dose) meningococcal A (Men A) conjugate vaccine through an innovative international partnership that saw transfer of a conjugation and fermentation technology to a developing country vaccine manufacturer. A Phase 1 study of the vaccine in India has shown that the product is safe and immunogenic. Phase 2 studies have begun in Africa, and a large demonstration study of the conjugate vaccine is envisioned for 2008-2009. After extensive consultations with African public health officials a vaccine introduction plan has been developed that includes introduction of the Men A conjugate vaccine into standard Expanded Programme on Immunization (EPI) schedules but also emphasizes mass vaccination of 1-29 years old to induce herd immunity, a strategy that has been shown to be highly effective when the meningococcal C (Men C) conjugate vaccine was introduced in several European countries. The MVP model is a clear example of the usefulness of a "push mechanism" to finance the development of a needed vaccine for the developing world.
Willis, Natalie; Hill, Sophie; Kaufman, Jessica; Lewin, Simon; Kis-Rigo, John; De Castro Freire, Sara Bensaude; Bosch-Capblanch, Xavier; Glenton, Claire; Lin, Vivian; Robinson, Priscilla; Wiysonge, Charles S
Vaccination is a cost-effective public health measure and is central to the Millennium Development Goal of reducing child mortality. However, childhood vaccination coverage remains sub-optimal in many settings. While communication is a key feature of vaccination programmes, we are not aware of any comprehensive approach to organising the broad range of communication interventions that can be delivered to parents and communities to improve vaccination coverage. Developing a classification system (taxonomy) organised into conceptually similar categories will aid in: understanding the relationships between different types of communication interventions; facilitating conceptual mapping of these interventions; clarifying the key purposes and features of interventions to aid implementation and evaluation; and identifying areas where evidence is strong and where there are gaps. This paper reports on the development of the 'Communicate to vaccinate' taxonomy. The taxonomy was developed in two stages. Stage 1 included: 1) forming an advisory group; 2) searching for descriptions of interventions in trials (CENTRAL database) and general health literature (Medline); 3) developing a sampling strategy; 4) screening the search results; 5) developing a data extraction form; and 6) extracting intervention data. Stage 2 included: 1) grouping the interventions according to purpose; 2) holding deliberative forums in English and French with key vaccination stakeholders to gather feedback; 3) conducting a targeted search of grey literature to supplement the taxonomy; 4) finalising the taxonomy based on the input provided. The taxonomy includes seven main categories of communication interventions: inform or educate, remind or recall, teach skills, provide support, facilitate decision making, enable communication and enhance community ownership. These categories are broken down into 43 intervention types across three target groups: parents or soon-to-be-parents; communities, community
... Vaccine Information Materials for Rotavirus Vaccine AGENCY: Centers for Disease Control and Prevention... information materials for rotavirus vaccine. DATES: Written comments are invited and must be received on or... (chickenpox), pneumococcal conjugate, rotavirus, hepatitis A, meningococcal, human papillomavirus (HPV), and...
Full Text Available Edible vaccines hold great promise as a cost-effective, easy-to-administer, easy-to-store, fail-safe and socioculturally readily acceptable vaccine delivery system, especially for the poor developing countries. It involves introduction of selected desired genes into plants and then inducing these altered plants to manufacture the encoded proteins. Introduced as a concept about a decade ago, it has become a reality today. A variety of delivery systems have been developed. Initially thought to be useful only for preventing infectious diseases, it has also found application in prevention of autoimmune diseases, birth control, cancer therapy, etc. Edible vaccines are currently being developed for a number of human and animal diseases. There is growing acceptance of transgenic crops in both industrial and developing countries. Resistance to genetically modified foods may affect the future of edible vaccines. They have passed the major hurdles in the path of an emerging vaccine technology. Various technical obstacles, regulatory and non-scientific challenges, though all seem surmountable, need to be overcome. This review attempts to discuss the current status and future of this new preventive modality.
Full Text Available Although rabies incidence has fallen sharply over the past decades in Europe, the disease is still present in Eastern Europe. Oral rabies immunization of wild animal rabies has been shown to be the most effective method for the control and elimination of rabies. All rabies vaccines used in Europe are modified live virus vaccines based on the Street Alabama Dufferin (SAD strain isolated from a naturally-infected dog in 1935. Because of the potential safety risk of a live virus which could revert to virulence, the genetic composition of three commercial attenuated live rabies vaccines was investigated in two independent laboratories using next genome sequencing. This study is the first one reporting on the diversity of variants in oral rabies vaccines as well as the presence of a mix of at least two different variants in all tested batches. The results demonstrate the need for vaccine producers to use new robust methodologies in the context of their routine vaccine quality controls prior to market release.
Identification of a new genetic marker in Mycoplasma synoviae vaccine strain MS-H and development of a strategy using polymerase chain reaction and high-resolution melting curve analysis for differentiating MS-H from field strains.
Zhu, Ling; Konsak, Barbara M; Olaogun, Olusola M; Agnew-Crumptona, Rebecca; Kanci, Anna; Marenda, Marc S; Browning, Glenn F; Noormohammadi, Amir H
Mycoplasma synoviae (MS) is an economically important avian pathogen worldwide, causing subclinical respiratory tract infection and infectious synovitis in chickens and turkeys. A temperature-sensitive (ts + ) live attenuated vaccine MS-H, derived from the Australian field strain 86079/7NS, is now widely used in many countries to control the disease induced by MS. Differentiation of MS-H vaccine from field strains is crucial for monitoring vaccination programs in commercial poultry. Comparison of genomic sequences of MS-H and its parent strain revealed an adenine deletion at nucleotide position 468 of the MS-H oppF-1 gene. This mutation was shown to be unique to MS-H in further comparative analyses of oppF-1 genes of MS-H re-isolates and field strains from Australia and other countries. Based on this single nucleotide, a combination of nested PCR and high-resolution melting (HRM) curve analysis was used to evaluate its potential for use in differentiation of MS-H from field strains. The mean genotype confidence percentages of 99.27 and 48.20 for MS-H and field strains, respectively, demonstrated the high discriminative power of the newly developed assay (oppF PCR-HRM). A set of 13 tracheal swab samples collected from MS-H vaccinated specific pathogen free birds and commercial chicken flocks infected with MS were tested using the oppF PCR-HRM test and results were totally consistent with those obtained using vlhA genotyping. The nested-PCR HRM method established in this study proved to be a rapid, simple and cost effective tool for discriminating the MS-H vaccine strain from Australian and international strains in pure cultures and on tracheal swabs. Copyright © 2017 Elsevier B.V. All rights reserved.
Ratanasuwan, W; Kim, Y H; Sah, B K; Suwanagool, S; Kim, D R; Anekthananon, A; Lopez, A L; Techasathit, W; Grahek, S L; Clemens, J D; Wierzba, T F
Many areas with endemic and epidemic cholera report significant levels of HIV transmission. According to the World Health Organization (WHO), over 95% of reported cholera cases occur in Africa, which also accounts for nearly 70% of people living with HIV/AIDS globally. Peru-15, a promising single dose live attenuated oral cholera vaccine (LA-OCV), was previously found to be safe and immunogenic in cholera endemic areas. However, no data on the vaccine's safety among HIV-seropositive adults had been collected. This study was a double-blinded, individually randomized, placebo-controlled trial enrolling HIV-seropositive adults, 18-45 years of age, conducted in Bangkok, Thailand, to assess the safety of Peru-15 in a HIV-seropositive cohort. 32 HIV infected subjects were randomized to receive either a single oral dose of the Peru-15 vaccine with a buffer or a placebo (buffer only). No serious adverse events were reported during the follow-up period in either group. The geometric mean fold (GMF) rise in V. cholerae O1 El Tor specific antibody titers between baseline and 7 days after dosing was 32.0 (pcholerae was isolated from the stool of one vaccinee, and found to be genetically identical to the Peru-15 vaccine strain. There were no significant changes in HIV viral load or CD4 T-cell counts between vaccine and placebo groups. Peru-15 was shown to be safe and immunogenic in HIV-seropositive Thai adults. Copyright © 2015 Elsevier Ltd. All rights reserved.
EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2014. Scientific Opinion on lipase from a genetically modified strain of Aspergillus oryzae (strain NZYM-FL)
Poulsen, Morten; Hallas-Møller, Torben; Binderup, Mona-Lise
The food enzyme considered in this opinion is a lipase (triacylglycerol lipase; EC 220.127.116.11) produced with a genetically modified strain of Aspergillus oryzae. The genetic modifications do not raise safety concern. The food enzyme contains neither the production organism nor recombinant DNA...
... 21, 2014 Select a Language: Fact Sheet 158 AIDS Myths and Misunderstandings WHY ARE THERE SO MANY ... support this belief. Myth: Current medications can cure AIDS. It’s no big deal if you get infected. ...
... this page: //medlineplus.gov/ency/article/001958.htm First aid kit To use the sharing features on this ... ahead, you can create a well-stocked home first aid kit. Keep all of your supplies in one ...
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... Partner Spotlight Awareness Days Get Tested Find an HIV testing site near you. Enter ZIP code or ... AIDS Get Email Updates on AAA Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content Podcasts Slide Sets ...
... et al., eds. American Medical Association Handbook of First Aid and Emergency Care. New York: Random House; 2009. Accessed July 21, 2017. Piazza GM, et al. First Aid Manual. 3rd ed. London, England; New York, N. ...
... aids : Most parts are contained in a small plastic case that rests behind the ear; the case ... certain situations (for example, background noise and whistle reduction). They also have greater flexibility in hearing aid ...
... for Educators Search English Español First Aid: The Flu KidsHealth / For Parents / First Aid: The Flu Print ... tiredness What to Do If Your Child Has Flu Symptoms: Call your doctor. Encourage rest. Keep your ...
Josefsberg, Jessica O; Buckland, Barry
The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory
The Medical Service once again recommends you to get your annual flu vaccination for the year. Vaccination is the most effective way of avoiding the illness and any serious consequences and protecting those around you. The flu can have especially serious consequences for people with chronic conditions (diabetes, cardio-vascular disease, etc.), pregnant women, infants, and people over 65 years of age. Remember, anyone working on the CERN site who wishes to be vaccinated against seasonal flu should go to the Infirmary (Building 57, ground floor) with their vaccine. The Medical Service will issue a prescription on the day of the vaccination for the purposes of reimbursement by UNIQA. NB: The Medical Service cannot provide this vaccination service for family members or retired members of the personnel. For more information: • The "Seasonal flu" flyer by the Medical Service • Recommendations of the Swiss Federal Office of Public...
Zhang, Jun; Zhao, Qinjian; Xia, Ningshao
Hepatitis E has been increasingly recognized as an underestimated global disease burden in recent years. Subpopulations with more serious infection-associated damage or death include pregnant women, patients with basic liver diseases, and elderly persons. Vaccine would be the most effective means for prevention of HEV infection. The lack of an efficient cell culture system for HEV makes the development of classic inactive or attenuated vaccine infeasible. Hence, the recombinant vaccine approaches are explored deeply. The neutralizing sites are located almost exclusively in the capsid protein, pORF2, of the virion. Based on pORF2, many vaccine candidates showed potential of protecting primate animals; two of them were tested in human and evidenced to be well tolerated in adults and highly efficacious in preventing hepatitis E. The world's first hepatitis E vaccine, Hecolin ® (HEV 239 vaccine), was licensed in China and launched in 2012.
Full Text Available Active immunization of children has been proven very effective in elimination of life threatening complications of many infectious diseases in developed countries. However, as vaccination-preventable infectious diseases and their complications have become rare, the interest focuses on immunization-related adverse reactions. Unfortunately, fear of vaccination-related adverse effects can led to decreased vaccination coverage and subsequent epidemics of infectious diseases. This review includes reports about possible side effects following vaccinations in children with neurological disorders and also published recommendations about vaccinating children with neurological disorders. From all international published data anyone can conclude that vaccines are safer than ever before, but the challenge remains to convey this message to society.
Esposito, Susanna; Bianchini, Sonia; Dellepiane, Rosa Maria; Principi, Nicola
The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.
Lithgow, Karen V; Cameron, Caroline E
Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a globally prevalent disease despite remaining susceptible to penicillin treatment. Syphilis vaccine development is a viable preventative approach that will serve to complement public health-oriented syphilis prevention, screening and treatment initiatives to deliver a two-pronged approach to stemming disease spread worldwide. Areas covered: This article provides an overview of the need for development of a syphilis vaccine, summarizes significant information that has been garnered from prior syphilis vaccine studies, discusses the critical aspects of infection that would have to be targeted by a syphilis vaccine, and presents the current understanding within the field of the correlates of protection needed to be achieved through vaccination. Expert commentary: Syphilis vaccine development should be considered a priority by industry, regulatory and funding agencies, and should be appropriately promoted and supported.
Barraza, Leila; Schmit, Cason; Hoss, Aila
This paper discusses recent changes to state legal frameworks for mandatory vaccination in the context of school and healthcare worker vaccination. It then discusses state laws that allow pharmacists the authority to vaccinate.
Amorij, Jean-Pierre; Hinrichs, Wouter L.J.; Frijlink, Henderik W.; Wilschut, Jan C.; Huckriede, Anke
Vaccination is the cornerstone of influenza control in epidemic and pandemic situations. Influenza vaccines are typically given by intramuscular injection. However, needle-free vaccinations could offer several distinct advantages over intramuscular injections: they are pain-free, easier to
... Recommendations Why Immunize? Vaccines: The Basics The Adult Vaccine Quiz Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Vaccines are recommended for adults based on age, health ...
... Vaccination Resources for Healthcare Professionals Recommended Vaccines for Healthcare Workers Recommend on Facebook Tweet Share Compartir On ... for More Information Resources for Those Vaccinating HCWs Healthcare workers (HCWs) are at risk for exposure to ...
Johansen, Helle Krogh; Gøtzsche, Peter C
Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. This is an update of a previously published review. To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30 March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013). Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis. The authors independently selected trials, assessed them and extracted data. Six trials were identified. Two trials were excluded since they were not randomised and one old, small trial because it was not possible to assess whether is was randomised. The three included trials comprised 483, 476 and 37 patients, respectively. No data have been published from one of the large trials, but the company stated in a press release that the trial failed to confirm the results from an earlier study and that further clinical development was suspended. In the other large trial, relative risk for chronic infection was 0.91 (95% confidence interval 0.55 to 1.49), and in the small trial, the risk was also close to one. In the large trial, one patient was reported to have died in the observation period. In that trial, 227 adverse events (4 severe) were registered in the vaccine group and 91 (1 severe) in the control group. In this large trial of a vaccine developed against flagella antigens, antibody titres against the epitopes contained in the vaccine were higher in the vaccine group compared to the placebo group (P Vaccines against
Linhares Alexandre C.
Full Text Available Worldwide, rotaviruses account for more than 125 million cases of infantile gastroenteritis and nearly 1 million deaths per year, mainly in developing countries. Rather than other control measures, vaccination is most likely to have a major impact on rotavirus disease incidence. The peak incidence of rotavirus diarrhea occurs between 6 and 24 months of age. In developing countries, however, cases are not uncommon among children younger than 6 months. G serotypes 1 to 4 are responsible for most disease, but there are indications that in Brazil that G type 5 is of emerging epidemiological importance. Both homotypic and heterotypic responses are elicited during natural rotavirus infection, and the immunological response at the intestinal mucosal surface is probably the more consistent predictor of clinical immunity. With the primary objective of protecting children against life-threatening dehydrating diarrhea, many approaches to rotavirus vaccine development have been attempted. One vaccine, the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV, was given licensing approval in the United States of America, introduced to the market, and later withdrawn. A number of studies have found better efficacy of RRV-TV in developed countries than in developing ones. Field trials with a 4 X 10(4 plaque-forming units (PFU preparation of RRV-TV have been carried out in two countries in Latin America, Brazil and Peru. Those trials yielded protective efficacy rates against all rotavirus diarrhea ranging from 18% to 35%. Data from a large catchment trial in Venezuela with a higher RRV-TV dose, of 4 X 10(5 PFU/dose, indicated an efficacy rate of 48% against all rotavirus diarrhea and 88% against severe rotavirus diarrhea. It appears that breast-feeding does not compromise the efficacy of RRV-TV if three doses of the vaccine are administered. Similarly, possible interference of oral poliovirus vaccine with the "take" of the rotavirus vaccine can be
Alexandre C. Linhares
Full Text Available Worldwide, rotaviruses account for more than 125 million cases of infantile gastroenteritis and nearly 1 million deaths per year, mainly in developing countries. Rather than other control measures, vaccination is most likely to have a major impact on rotavirus disease incidence. The peak incidence of rotavirus diarrhea occurs between 6 and 24 months of age. In developing countries, however, cases are not uncommon among children younger than 6 months. G serotypes 1 to 4 are responsible for most disease, but there are indications that in Brazil that G type 5 is of emerging epidemiological importance. Both homotypic and heterotypic responses are elicited during natural rotavirus infection, and the immunological response at the intestinal mucosal surface is probably the more consistent predictor of clinical immunity. With the primary objective of protecting children against life-threatening dehydrating diarrhea, many approaches to rotavirus vaccine development have been attempted. One vaccine, the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV, was given licensing approval in the United States of America, introduced to the market, and later withdrawn. A number of studies have found better efficacy of RRV-TV in developed countries than in developing ones. Field trials with a 4 X 10(4 plaque-forming units (PFU preparation of RRV-TV have been carried out in two countries in Latin America, Brazil and Peru. Those trials yielded protective efficacy rates against all rotavirus diarrhea ranging from 18% to 35%. Data from a large catchment trial in Venezuela with a higher RRV-TV dose, of 4 X 10(5 PFU/dose, indicated an efficacy rate of 48% against all rotavirus diarrhea and 88% against severe rotavirus diarrhea. It appears that breast-feeding does not compromise the efficacy of RRV-TV if three doses of the vaccine are administered. Similarly, possible interference of oral poliovirus vaccine with the "take" of the rotavirus vaccine can be
19 Feb 1983 ... deal with immunological changes in haemophiliacs similar to those in AIDS and indicate that a number of these patients may be at special risk, a finding supported by a report> of 3 ca es of AIDS identified in heterosexual haemophiliacs. An even more baffling finding is that AIDS is more prevalent in ...
... 12, 2017. Jevon P, et al. Part 5 — First-aid treatment for severe bleeding. Nursing Times. 2008;104:26. Oct. 19, 2017 Original article: http://www.mayoclinic.org/first-aid/first-aid-severe-bleeding/basics/ART-20056661 . Mayo ...
... Skin problems. In: American Medical Association Handbook of First Aid and Emergency Care. New York, N.Y.: Random House; 2009. Jan. 12, 2018 Original article: http://www.mayoclinic.org/first-aid/first-aid-puncture-wounds/basics/ART-20056665 . Mayo ...
Buiren, K.; Brouwer, E.
From economic theory we derive a set of hypotheses on the determination of state aid. Econometric analysis on EU state aid panel data is carried out to test whether the determinants we expect on the basis of theory, correspond to the occurrence of state aid in practice in the EU. We find that
This document gives an overview of the worldwide spread of acquired immune deficiency syndrome (AIDS), the means of its prevention, and its effects on women who are not infected. It also explains how the AIDS virus is not spread, and why it is important not to be afraid of those infected with the AIDS virus. It stresses the need for information at a time when a vaccine or cure are not yet available, and education is the only means of prevention. The global mobilization being conducted to fight the AIDS crisis is discussed. Different ways in which women are at risk to infection by the HIV virus are reviewed, especially the subordination of women. This denies them the same education, legal rights, training, health, and independent incomes, all of which reduces their chance for access to information about AIDS. It considers risk of being infected by a partner, from a blood transfusion, increased susceptibility in someone who already has a sexually transmitted disease, increased susceptibility in a woman who has been circumcised, risk of infection from rape, and how women are coerced into prostitution, putting them at risk for AIDS. It also covers HIV infection and contraception, the danger to professional health-care workers, transmission of HIV infection from mother-to-infant, and discrimination that is AIDS-related. Women who are not infected are impacted by AIDS because they suffer stress as caretakers. The document also discusses the social and economic consequences of AIDS.
Lee, Bruce Y; McGlone, Sarah M
New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following eleven components: (1) Conduct a target population analysis; (2) Map potential competitors and alternatives; (3) Construct a vaccine targe...
Marshall K. Cheney
Full Text Available Yearly influenza vaccination continues to be underutilized by those who would most benefit from it. The Health Belief Model was used to explain differences in beliefs about influenza vaccination among at-risk individuals resistant to influenza vaccination. Survey data were collected from 74 members of at-risk groups who were not vaccinated for influenza during the previous flu season. Accepting individuals were more likely to perceive flu as a threat to health and perceive access barriers, and cues to action were the most important influence on whether they plan to get vaccinated. In comparison, resistant individuals did not feel threatened by the flu, access barriers were not a problem, and they did not respond favorably to cues to action. Perceived threat, perceived access barriers, and cues to action were significantly associated with plans to be vaccinated for influenza in the next flu season. Participants who saw influenza as a threat to their health had 5.4 times the odds of planning to be vaccinated than those who did not. Participants reporting barriers to accessing influenza vaccination had 7.5 times the odds of reporting plans to be vaccinated. Those responding positively to cues to action had 12.2 times the odds of planning to be vaccinated in the next flu season than those who did not. Accepting and resistant individuals have significant differences in their beliefs, which require different intervention strategies to increase vaccination rates. These findings provide important information to researchers and practitioners working to increase influenza vaccination rates.
Dudas, Robert A.; Karron, Ruth A.
Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness (LRI) in infants and children worldwide and causes significant LRI in the elderly and in immunocompromised patients. The goal of RSV vaccination is to prevent serious RSV-associated LRI. There are several obstacles to the development of successful RSV vaccines, including the need to immunize very young infants, who may respond inadequately to vaccination; the existence of two antigenically d...
Hilleman, M R
The sciences of vaccinology and immunology were created only two centuries ago by Jenner's scientific studies of prevention of smallpox through inoculation with cowpox virus. This rudimentary beginning was expanded greatly by the giants of late 19th- and early 20th-century biomedical sciences. The period from 1930 to 1950 was a transitional era, with the introduction of chick embryos and minced tissues for propagating viruses and rickettsiae in vitro for vaccines. Modern vaccinology began about 1950 as a continuum following notable advances made during the 1940s and World War II. Its pursuit has been based largely on breakthroughs in cell culture, bacterial polysaccharide chemistry, molecular biology, and immunology which have yielded many live and killed viral and bacterial vaccines plus the recombinant-expressed hepatitis B vaccine. The present paper was presented as a lecture given at a Meeting of the Institute of Human Virology entitled A Symposium on HIV-AIDS and Cancer Biology, Baltimore, Maryland, on August 30, 1999 and recounts, by invitation, more than 55 years of vaccine research from the venue of personal experience and attainment by the author. The paper is intentionally brief and truncated with focus only on highlights and limited referencing. Detailed recounting and referencing are given elsewhere in text references 1 and 2. This narration will have achieved its purpose if it provides a background of understanding and guidelines that will assist others who seek to engage in creation of new vaccines.
Pagliusi, Sonia; Jain, Rishabh; Suri, Rajinder Kumar
The Developing Countries Vaccine Manufacturers' Network (DCVMN) held its fifteenth annual meeting from October 27-29, 2014, New Delhi, India. The DCVMN, together with the co-organizing institution Panacea Biotec, welcomed over 240 delegates representing high-profile governmental and nongovernmental global health organizations from 36 countries. Over the three-day meeting, attendees exchanged information about their efforts to achieve their shared goal of preventing death and disability from known and emerging infectious diseases. Special praise was extended to all stakeholders involved in the success of polio eradication in South East Asia and highlighted challenges in vaccine supply for measles-rubella immunization over the coming decades. Innovative vaccines and vaccine delivery technologies indicated creative solutions for achieving global immunization goals. Discussions were focused on three major themes including regulatory challenges for developing countries that may be overcome with better communication; global collaborations and partnerships for leveraging investments and enable uninterrupted supply of affordable and suitable vaccines; and leading innovation in vaccines difficult to develop, such as dengue, Chikungunya, typhoid-conjugated and EV71, and needle-free technologies that may speed up vaccine delivery. Moving further into the Decade of Vaccines, participants renewed their commitment to shared responsibility toward a world free of vaccine-preventable diseases. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Pagliusi, Sonia; Ting, Ching-Chia; Lobos, Fernando
The Developing Countries Vaccine Manufacturers' Network (DCVMN) gathered leaders in immunization programs, vaccine manufacturing, representatives of the Argentinean Health Authorities and Pan American Health Organization, among other global health stakeholders, for its 17th Annual General Meeting in Buenos Aires, to reflect on how vaccines are shaping global health. Polio eradication and elimination of measles and rubella from the Americas is a result of successful collaboration, made possible by timely supply of affordable vaccines. After decades of intense competition for high-value markets, collaboration with developing countries has become critical, and involvement of multiple manufacturers as well as public- and private-sector investments are essential, for developing new vaccines against emerging infectious diseases. The recent Zika virus outbreak and the accelerated Ebola vaccine development exemplify the need for international partnerships to combat infectious diseases. A new player, Coalition for Epidemic Preparedness Innovations (CEPI) has made its entrance in the global health community, aiming to stimulate research preparedness against emerging infections. Face-to-face panel discussions facilitated the dialogue around challenges, such as risks of viability to vaccine development and regulatory convergence, to improve access to sustainable vaccine supply. It was discussed that joint efforts to optimizing regulatory pathways in developing countries, reducing registration time by up to 50%, are required. Outbreaks of emerging infections and the global Polio eradication and containment challenges are reminders of the importance of vaccines' access, and of the importance of new public-private partnerships. Copyright © 2017.
Three or four general strategies are adopted for the control of infectious diseases. Early diagnosis, vaccination and chemotherapy. In the situations where there is transfer through mosquitoes or ticks from alternate hosts, control of the vector and of the infection in the alternate host are additional measures to be taken. This Chapter looks at the problems of disease control from the perspective of genetics, since molecular genetics now provides powerful tools in the form of radiolabelled DNA probes and clones of selected segments, useful for diagnosis as well as for vaccine design
Notani, N K
Three or four general strategies are adopted for the control of infectious diseases. Early diagnosis, vaccination and chemotherapy. In the situations where there is transfer through mosquitoes or ticks from alternate hosts, control of the vector and of the infection in the alternate host are additional measures to be taken. This Chapter looks at the problems of disease control from the perspective of genetics, since molecular genetics now provides powerful tools in the form of radiolabelled DNA probes and clones of selected segments, useful for diagnosis as well as for vaccine design
Oyarzún, Patricio; Kobe, Bostjan
Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.
Full Text Available Francisella tularensis is a facultative intracellular pathogen that causes the disease tularemia. F. tularensis subsp. tularensis causes the most severe disease in humans and has been classified as a select A agent and potential bioweapon. There is currently no vaccine approved for human use, making genetic manipulation of this organism critical to unraveling the genetic basis of pathogenesis and developing countermeasures against tularemia. The development of genetic techniques applicable to F. tularensis have lagged behind those routinely used for other bacteria, primarily due to lack of research and the restricted nature of the biocontainment required for studying this pathogen. However, in recent years, genetic techniques, such as transposon mutagenesis and targeted gene disruption, have been developed, that have had a dramatic impact on our understanding of the genetic basis of F. tularensis virulence. In this review, we describe some of the methods developed for genetic manipulation of F. tularensis.
Adacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Boostrix® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)
evolved since World War II in response to a dramatically changing global political and economic context. I review the aid process and associated trends in the volume and distribution of aid and categorize some of the key goals, principles and institutions of the aid system. The evidence on whether aid has...... been effective in furthering economic growth and development is discussed in some detail. I add perspective and identify some critical unresolved issues. I finally turn to the current development debate and discuss some key concerns, I believe should be kept in mind in formulating any agenda for aid...
Inaya eHajj Hussein
Full Text Available Multiple cornerstones have shaped the history of vaccines, which may contain live attenuated viruses, inactivated organisms/viruses, inactivated toxins, or merely segments of the pathogen that could elicit an immune response.The story began with Hippocrates 400 B.C. with his description of mumps and diphtheria. No further discoveries were recorded until 1100 A.D. when the smallpox vaccine was described. During the 18th century, vaccines for cholera and yellow fever were reported and Edward Jenner, the father of vaccination and immunology, published his work on small pox.The 19th century was a major landmark, with the Germ Theory of disease of Louis Pasteur, the discovery of the germ tubercle bacillus for tuberculosis by Robert Koch, and the isolation of pneumococcus organism by George Miller Sternberg. Another landmark was the discovery of diphtheria toxin by Emile Roux and its serological treatment by Emil Von Behring and Paul Ehrlih. In addition, Pasteur was able to generate the first live attenuated viral vaccine against rabies. Typhoid vaccines were then developed, followed by the plague vaccine of Yersin. At the beginning of World War I, the tetanus toxoid was introduced, followed in 1915 by the pertussis vaccine. In 1974, The Expanded Program of Immunization was established within the WHO for BCG, Polio, DTP, measles, yellow fever and hepatitis B. The year 1996 witnessed the launching of the International AIDS Vaccine Initiative. In 1988, the WHO passed a resolution to eradicate polio by the year 2000 and in 2006; the first vaccine to prevent cervical cancer was developed. In 2010 The Decade of vaccines was launched, and on April 1st 2012, the United Nations launched the shot@Life campaign. In brief, the armamentarium of vaccines continues to grow with more emphasis on safety, availability and accessibility. This mini review highlights the major historical events and pioneers in the course of development of vaccines, which have eradicated
Full Text Available The concepts, targets, tools, institutions and modes of operation of official development assistance have been overtaken by the pace of change in a world marked by the combined momentum of demography, technology and economic growth.Aid can however recover, as social consequences of the globalization call for new forms of regulation. It will then be necessary to modify and diversify our target-setting processes, to update operating procedures, and to find better ways of measuring policy implementation. Aid volumes will certainly continue to grow, and we must transform the way aid is financed. Public and private aid stakeholders must recognize the importance of these transformations and be ready to support them, by questioning the methods as well as the objectives of the policies they are implementing. Otherwise, they will severely impede the emergence of the policies we need if we are to build a better world.
In the present study, the prevention of cancer development by vaccination with fusion cells was evaluated In a genetically engineered murine model which develops spontaneous mammary carcinomas. The mice (MMT...
J Gordon Millichap
Full Text Available Serious neurological disorders reported following whole-cell (WC in comparison to acellular (AC pertussis vaccines (PV were evaluated by the Genetic Centers of America, Silver Spring, MD.
Soema, Peter Christiaan
Current seasonal influenza vaccines rely on the induction of antibodies to neutralize the virus. However, influenza viruses frequently undergo genetic mutations due to antigenic drift and shift, altering the surface proteins hemagglutinin and neuraminidase to which antibodies usually bind. This
Doucouliagos, Hristos; Paldam, Martin
The AEL (aid effectiveness literature) is econo¬metric studies of the macroeconomic effects of development aid. It contains about 100 papers of which 68 are reduced form estimates of theeffect of aid on growth in the recipient country. The raw data show that growth is unconnected to aid......, but the AEL has put so much structure on the data that all results possible have emerged. The present meta study considers both the best-set of the 68 papers and the all-set of 543 regressions published. Both sets have a positive average aid-growth elasticity, but it is small and insignificant: The AEL has...... betweenstudies is real. In particular, the aid-growth association is stronger for Asian countries, and the aid-growth association is shown to have been weaker in the 1970s....
First aid Fractures (broken bones) Fractures (broken bones): First aid By Mayo Clinic Staff A fracture is a ... 10, 2018 Original article: http://www.mayoclinic.org/first-aid/first-aid-fractures/basics/ART-20056641 . Mayo Clinic ...
The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751
Hotez, Peter J; Diemert, David; Bacon, Kristina M; Beaumier, Coreen; Bethony, Jeffrey M; Bottazzi, Maria Elena; Brooker, Simon; Couto, Artur Roberto; Freire, Marcos da Silva; Homma, Akira; Lee, Bruce Y; Loukas, Alex; Loblack, Marva; Morel, Carlos Medicis; Oliveira, Rodrigo Correa; Russell, Philip K
Hookworm infection is one of the world's most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries. A Human Hookworm Vaccine is currently being developed by the Sabin Vaccine Institute and is in phase 1 clinical testing. The candidate vaccine is comprised of two recombinant antigens known as Na-GST-1 and Na-APR-1, each of which is an important parasite enzyme required for hookworms to successfully utilize host blood as a source of energy. The recombinant proteins are formulated on Alhydrogel(®) and are being tested in combination with a synthetic Toll-like receptor 4 agonist. The aim of the vaccine is to induce anti-enzyme antibodies that will reduce both host blood loss and the number of hookworms attached to the gut. Transfer of the manufacturing technology to the Oswaldo Cruz Foundation (FIOCRUZ)/Bio-Manguinhos (a Brazilian public sector developing country vaccine manufacturer) is planned, with a clinical development plan that could lead to registration of the vaccine in Brazil. The vaccine would also need to be introduced in the poorest regions of Africa and Asia, where hookworm infection is highly endemic. Ultimately, the vaccine could become an essential tool for achieving hookworm control and elimination, a key target in the 2012 London Declaration on Neglected Tropical Diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.
Lee, Bruce Y; McGlone, Sarah M
New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical, and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following ten components: 1. Conduct a target population analysis; 2. Map potential competitors and alternatives; 3. Construct a vaccine target product profile (TPP) and compare it to projected or actual TPPs of competing vaccines; 4. Quantify the incremental value of the new vaccine's characteristics; 5. Determine vaccine positioning in the marketplace; 6. Estimate the vaccine price-demand curve; 7. Calculate vaccine costs (including those of manufacturing, distribution, and research and development); 8. Account for various legal, regulatory, third party payer, and competitor factors; 9. Consider the overall product portfolio; 10. Set pricing objectives; 11. Select pricing and pricing structure. While the biomedical literature contains some studies that have addressed these components, there is still considerable room for more extensive evaluation of this important area.
McGlone, Sarah M
New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following 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
Lehmann, B.; Eilers, R.; Donken, R.; Barug, D.; Swillens, J.; Vriend, C. de; Weerdenburg, S.; Pot, M.; Keulen, H. van; Paulussen, T.; Vermey, K.; Alberts, N.; Marra, E.; Melker, H.E. de; Mollema, L.
Both in 2013 and 2015 the mean intention of parents to vaccinate their child was high. Only 21% of parents reported making an informed decision about childhood vaccinations included in the NIP. Mass media attention on the use of allegedly inferior needles, which was later refuted, appeared to have a
... the disease no longer exists. If we keep vaccinating now, parents in the future may be able to trust that diseases like polio and meningitis won't infect, cripple, or kill children. Vaccine Safety In light of recent questions about ...
Rolland, M.; Magaret, C.A.; Rademeyer, C.; Fiore-Gartland, A.; Edlefsen, P.T.; DeCamp, A.; Ahmed, H.; Ngandu, N.; Larsen, B.B.; Frahm, N.; Marais, J.; Thebus, R.; Geraghty, D.; Hural, J.; Corey, L.; Kublin, J.; Gray, G.; McElrath, M.J.; Mullins, J.I.; Gilbert, P.B.; Williamson, C.
Introduction The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. Materials and methods A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert. Results There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p = 0.045) and Nef (p = 0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p sieve effect in Step was driven by HLA A*02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively. Discussion This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes. PMID:27756485
Jadhav, Emmanuel D; Winkler, Danielle L; Anderson, Billie S
The resurgence of vaccine preventable diseases occurs more often among intentionally unvaccinated individuals, placing at direct risk young adults not caught up on vaccinations. The objectives of this study were to characterize the sociodemographic characteristics of young adults with and without vaccination waivers and identify their perceived benefits, barriers, and influencers of vaccination. Young adults ( n = 964) from a Midwestern rural university responded to a survey (fall 2015-spring 2016) designed to identify their perception toward vaccination. Instrument consistency was measured using the Cronbach α-scores. The Chi-square test was used to test any sociodemographic differences and Mann-Whitney U -tests results for differences between exempt and non-exempt students. Analysis occurred in spring 2017. A little over one-third of young adults with a vaccination waiver were not up to date on their vaccinations, and think that vaccinations can cause autism. The biggest identifiable benefit was effective control against disease. The surveyed young adults ranked the out of pocket cost associated with vaccination as the most important barrier and safe and easy to use vaccines as the most important influencer of vaccination. Young adults who have had a vaccination waiver appear to not be up to date on their vaccinations. Vaccine administration programs, such as university campus clinics, would benefit from addressing perceptions unique to young adults with and without a vaccine waiver. This would subsequently better provide young adults a second shot for getting appropriately caught up on vaccinations.
Holst, Peter Johannes; Bassi, Maria Rosaria; Thomsen, Allan Randrup
DNA vaccines are versatile and safe, but limited immunogenicity has prevented their use in the clinical setting. Experimentally, immunogenicity may be enhanced by the use of new delivery technologies, by coadministration of cytokines and pathogen-associated molecular patterns, or by fusion...... of antigens into molecular domains that enhance antigen presentation. More specifically, the immunogenicity of DNA vaccines may benefit from increased protein synthesis, increased T-cell help and MHC class I presentation, and the addition of a range of specific cytokines and pathogen-associated molecular...... with viral-vectored vaccines, various synergistic components may need to be incorporated into DNA vaccines. From the perspective of the future clinical use of DNA vaccines, it has been suggested that antigen presentation should be improved and cytokine coadministration attempted. However, even...
Nelson, E Anthony S; Sack, David; Wolfson, Lara; Walker, Damian G; Seng, Lim Fong; Steele, Duncan
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.
Riedmann, Eva M
In February this year, about 100 delegates gathered for three days in Vienna (Austria) for the Next Generation Vaccines conference. The meeting held in the Vienna Hilton Hotel from 23rd-25th February 2011 had a strong focus on biotech and industry. The conference organizer Jacob Fleming managed to put together a versatile program ranging from the future generation of vaccines to manufacturing, vaccine distribution and delivery, to regulatory and public health issues. Carefully selected top industry experts presented first-hand experience and shared solutions for overcoming the latest challenges in the field of vaccinology. The program also included several case study presentations on novel vaccine candidates in different stages of development. An interactive pre-conference workshop as well as interactive panel discussions during the meeting allowed all delegates to gain new knowledge and become involved in lively discussions on timely, interesting and sometimes controversial topics related to vaccines.
Julik, Emily; Reyes-Del Valle, Jorge
Current measles vaccines suffer from poor effectiveness in young infants due primarily to the inhibitory effect of residual maternal immunity on vaccine responses. The development of a measles vaccine that resists such passive immunity would strongly contribute to the stalled effort toward measles eradication. In this concise communication, we show that a measles virus (MV) with enhanced hemagglutinin (H) expression and incorporation, termed MVvac2-H2, retained its enhanced immunogenicity, previously established in older mice, when administered to very young, genetically modified, MV-susceptible mice in the presence of passive anti-measles immunity. This immunity level mimics the sub-neutralizing immunity prevalent in infants too young to be vaccinated. Additionally, toward a more physiological small animal model of maternal anti-measles immunity interference, we document vertical transfer of passive anti-MV immunity in genetically-modified, MV susceptible mice and show in this physiological model a better MVvac2-H2 immunogenic profile than that of the parental vaccine strain. In sum, these data support the notion that enhancing MV hemagglutinin incorporation can circumvent in vivo neutralization. This strategy merits additional exploration as an alternative pediatric measles vaccine.
Duerr, Ann; Wasserheit, Judith N; Corey, Lawrence
A human immunodeficiency virus (HIV) vaccine is the most promising and feasible strategy to prevent the events during acute infection that simultaneously set the course of the epidemic in the community and the course of the disease for the individual. Because safety concerns limit the use of live, attenuated HIV and inactivated HIV, a variety of alternate approaches is being investigated. Traditional antibody-mediated approaches using recombinant HIV envelope proteins have shown no efficacy in 2 phase III trials. Current HIV vaccine trials are focusing primarily on cytotoxic T lymphocyte-mediated products that use viral vectors, either alone or as boosts to DNA plasmids that contain viral genes. The most immunogenic of these products appear to be the recombinant adenovirus vector vaccines, 2 of which are now in advanced clinical development.
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KAVI will offer training in epidemiology, research design, immunology, good clinical practice, good clinical ... enhance the capacity of local ethics review boards and institutional administrators to handle issues raised by ... Institution Website.
The development of an effective HIV vaccine has become a crucial national healthcare goal. To develop a worldwide AIDS vaccine, an international collaboration with developing countries is needed. The global approach rationale is threefold: millions of lives can be saved, a vaccine preparation can be tested more rapidly and economically among populations with high rates of infections; and the HIV epidemic comprises at least ten different subtypes. Although a number of barriers to the successful development of an HIV vaccine exist, the polio vaccine can be used as an example to show researchers how to overcome the obstacles. Jonas Salk, the polio vaccine developer, used killed whole virus in a technique that critics argued would not be fully effective. However, the Salk vaccine reduced polio-related paralysis by 72 percent, while the more effective Sabin oral vaccine did not become available until several years later. The lesson to be learned is that any percent of effectiveness is better than nothing, and researchers should not abandon uncertain HIV vaccine development efforts because they believe a better solution may develop in the future. The existence of traditional research should not preclude the development of new solutions that might prove more effective. For example, in the case of polio, the March of Dimes campaign pushed both the Salk and Sabin vaccines despite the skepticism of many academic research groups.
Ramirez, Jonathan C; Ackerman, Kimberly; Strain, Sasha C; Ahmed, Syed T; de Los Santos, Mario J; Sears, Dawn
Vaccinations against hepatitis A virus (HAV) and hepatitis B virus (HBV) are recommended for patients with chronic liver disease (CLD), yet implementation of these recommendations is lacking. This study reviewed HAV and HBV antibody testing and vaccination status of patients with CLD. In 2008, we began using pre-printed liver order sets, which included vaccination options. We compared Scott & White liver clinic CLD patient records from 2005 (238) with patient records from 2008 (792). Screening rates for immunity and vaccination rates of those lacking immunity were calculated. In 2005, 66% of CLD patients were screened for HAV immunity. In 2008, 56% of CLD patients were screened. The HAV vaccination completion rate was 37% in 2005, while in 2008, the rate was 46%. In 2005, 66% of CLD patients were screened for HBV immunity; in 2008, 56 % CLD patients were screened. The HBV vaccination completion rate was 26% in 2005 compared with 36% in 2008. Although there was a lower percentage of screening in 2008, the overall number of patients tripled between 2005 and 2008. There was a significant increase in the total number of patients screened and vaccinated in 2008. Some physicians may have vaccinated their patients without checking for immunity. In January 2008, we implemented pre-printed order sets with checkboxes to help remind providers to order labs to screen for immunity against HAV and HBV and to order vaccinations for those who lacked immunity. The use of these sets may have aided in the increase of vaccination completion rates.
Xu, Zhi-Yi; Wang, Xuan-Yi
Two live, attenuated hepatitis A vaccines, H2 and LA-1 virus strains, were developed through serial passages of the viruses in cell cultures at 32 °C and 35 °C respectively. Both vaccines were safe and immunogenic, providing protection against clinical hepatitis A in 95% of the vaccinees, with a single dose by subcutaneous injection. The vaccine recipients were not protected from asymptomatic, subclinical hepatitis A virus (HAV) infection, which induced a similar antibody response as for unvaccinated subjects. A second dose caused anamnestic response and can be used for boosting. Oral immunization of human with H2 vaccine or of marmoset with LA-1 vaccine failed, and no evidence was found for person-to-person transmission of H2 strain or for marmoset-to-marmoset transmission of LA-1 strain by close contact. H2 strain was genetically stable when passaged in marmosets, humans or cell cultures at 37 °C; 3 consecutive passages of the virus in marmosets did not cause virulence mutation. The live vaccines offer the benefits of low cost, single dose injection, long- term protection, and increased duration of immunity through subclinical infection. Improved sanitation and administration of 150 million doses of the live vaccines to children had led to a 90% reduction in the annual national incidence rate of hepatitis A in China during the 16-year period, from 1991 to 2006. Hepatitis A (HA) immunization with both live and inactivated HA vaccines was implemented in the national routine childhood immunization program in 2008 and around 92% of the 16 million annual births received the affordable live, attenuated vaccines at 18 months of age. Near elimination of the disease was achieved in a county of China for 14 years following introduction of the H2 live vaccine into the Expanded Immunization Program (EPI) in 1992. PMID:24280971
Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C
Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines. PMID:25424797
Clarisa B. Palatnik-De-Sousa
Full Text Available Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global-warming, co-infection with immunosuppressive diseases and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL in the Americas, the Middle East, Central Asia, China and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost-effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine visceral leishmaniasis. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans
World leaders, physicians, economists, governmental health organizations, and pharmaceutical manufacturers attended the Third International Conference on Healthcare Resource Allocation for HIV/AIDS and Other Life-threatening Illnesses in Vienna, Austria. The conference participants discussed the economic, ethical, and human rights issues underlying health care resource allocation. Some highlights of the meeting included: the prevention strategies in fighting AIDS virus; the use of high medical ethical standards; the affordability and accessibility of essential therapies; the economic aspects affecting the medical assistance mechanisms; the need to improve the pharmaceutical industry; the need to improve HIV/AIDS care access in developing countries; promoting the development of HIV/AIDS vaccines; and developing rapid diagnosis of HIV.
Laiskonis, Alvydas; Pukenyte, Evelina
Since 1980 more than 25 million people have died from acquired immunodeficiency syndrome (AIDS), which results from infection with human immunodeficiency virus (HIV). Number of new cases increases very threateningly. One and the most effective method to stop the progress of epidemic is the development of the vaccine for HIV. There is the presentation of the first stage of the vaccine for HIV testing (structure, methodology), which is now on trial in St. Pierre hospital, Brussels University. HIV characteristics which inflame the process of the vaccine development, historical facts and facts about vaccines on trial in these days are reviewed in this article. More than 10,000 volunteers have been participating in various clinical trials since 1987. The development of the vaccine is a very difficult, long-terming (about 8-10 years) and costly process. The process of the vaccine testing is very difficult in developing countries where the infection spreads the most rapidly. Available data confirm that the vaccine must be multi-componential, inducing cellular, humoral immunity against various subtypes of HIV. The vaccine cannot protect fully but the changes of the natural infection course could decrease virulence, distance the stage of AIDS, and retard the spread of the epidemic.
Arndt, Channing; Jones, Edward Samuel; Tarp, Finn
, are being drawn on the basis of fragile evidence. This paper first assesses the aid-growth literature with a focus on recent contributions. The aid-growth literature is then framed, for the first time, in terms of the Rubin Causal Model, applied at the macroeconomic level. Our results show that aid has......The micro-macro paradox has been revived. Despite broadly positive evaluations at the micro and meso-levels, recent literature has turned decidedly pessimistic with respect to the ability of foreign aid to foster economic growth. Policy implications, such as the complete cessation of aid to Africa...... a positive and statistically significant causal effect on growth over the long run with point estimates at levels suggested by growth theory. We conclude that aid remains an important tool for enhancing the development prospects of poor nations....
Czerwiec, M K
Matthew P. McAllister wrote: "Comic books can and have contributed positively to the discourse about AIDS: images that encourage true education, understanding and compassion can help cope with a biomedical condition which has more than a biomedical relevance" . With this in mind, I combined a 23-narrator oral history and my personal memoir about an inpatient Chicago AIDS hospital unit in my book, Taking Turns: Stories from HIV/AIDS Care Unit 371. In doing so, I built upon the existing rich history of HIV/AIDS in comics, which this article will briefly describe. Although not a comprehensive review of the intersection of AIDS and comics, the book is a tour through influences that proved useful to me. In addition, in making my book, I faced a distinct ethical issue with regard to representing patient experiences with HIV/AIDS, and I describe here how I addressed it. © 2018 American Medical Association. All Rights Reserved.
Most people do not react to vaccination and the incidence of vaccine anaphylaxis is estimated to be <1/million for all vaccines. 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 ...
Full Text Available Abstract Background Although routine vaccination is a major tool in the primary prevention of some infectious diseases, there is some reluctance in a proportion of the population. Negative parental perceptions of vaccination are an important barrier to paediatric vaccination. The aim of this study was to investigate parental knowledge of paediatric vaccines and vaccination in Catalonia. Methods A retrospective, cross-sectional study was carried out in children aged Results An association was observed between greater vaccination coverage of the 4:4:4:3:1 schedule (defined as: 4 DTPa/w doses, 4 Hib doses, 4 OPV doses, 3 MenC doses and 1 MMR dose and maternal age >30 years (OR: 2.30; 95% CI: 1.20–4.43 and with a knowledge of vaccination score greater than the mean (OR: 0.45; 95% CI: 0.28–0.72. The score increased with maternal educational level and in parents of vaccinated children. A total of 20.47% of parents stated that vaccines could have undesirable consequences for their children. Of these, 23.26% had no specific information and 17.83% stated that vaccines can cause adverse reactions and the same percentage stated that vaccines cause allergies and asthma. Conclusion Higher vaccination coverage is associated with older maternal age and greater knowledge of vaccination. Vaccination coverage could be raised by improving information on vaccines and vaccination.
Li, Xiao-Feng; Dong, Hao-Long; Wang, Hong-Jiang; Huang, Xing-Yao; Qiu, Ye-Feng; Ji, Xue; Ye, Qing; Li, Chunfeng; Liu, Yang; Deng, Yong-Qiang; Jiang, Tao; Cheng, Gong; Zhang, Fu-Chun; Davidson, Andrew D; Song, Ya-Jun; Shi, Pei-Yong; Qin, Cheng-Feng
The global spread of Zika virus (ZIKV) and its unexpected association with congenital defects necessitates the rapid development of a safe and effective vaccine. Here we report the development and characterization of a recombinant chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and genetic stability in vitro, while exhibiting an attenuation phenotype in multiple animal models. Remarkably, immunization of mice and rhesus macaques with a single dose of ChinZIKV elicits robust and long-lasting immune responses, and confers complete protection against ZIKV challenge. Significantly, female mice immunized with ChinZIKV are protected against placental and fetal damage upon ZIKV challenge during pregnancy. Overall, our study provides an alternative vaccine platform in response to the ZIKV emergency, and the safety, immunogenicity, and protection profiles of ChinZIKV warrant further clinical development.
Heylen, Elisabeth; Zeller, Mark; Ciarlet, Max; Lawrence, Jody; Steele, Duncan; Van Ranst, Marc; Matthijnssens, Jelle
RotaTeqTM is a pentavalent rotavirus vaccine based on a bovine rotavirus genetic backbone in vitro reassorted with human outer capsid genes. During clinical trials of RotaTeqTM in Sub-Saharan Africa, the vaccine efficacy over a 2-year follow-up was lower against the genotypes contained in the vaccine than against the heterotypic G8P and G8P rotavirus strains of which the former is highly prevalent in Africa. Complete genome analyses of 43 complete rotavirus genomes collected during phase III clinical trials of RotaTeqTM in Sub-Saharan Africa, were conducted to gain insight into the high level of cross-protection afforded by RotaTeqTM against these G8 strains. Phylogenetic analysis revealed the presence of a high number of bovine rotavirus gene segments in these human G8 strains. In addition, we performed an in depth analysis on the individual amino acid level which showed that G8 rotaviruses were more similar to the RotaTeqTM vaccine than non-G8 strains. Because RotaTeqTM possesses a bovine genetic backbone, the high vaccine efficacy against G8 strains might be partially explained by the fact that all these strains contain a complete or partial bovine-like backbone. Altogether, this study supports the hypothesis that gene segments other than VP7 and VP4 play a role in vaccine-induced immunity.
He, Yongqun; Xiang, Zuoshuang
Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis, one of the commonest zoonotic diseases found worldwide in humans and a variety of animal species. While several animal vaccines are available, there is no effective and safe vaccine for prevention of brucellosis in humans. VIOLIN (http://www.violinet.org) is a web-based vaccine database and analysis system that curates, stores, and analyzes published data of commercialized vaccines, and vaccines in clinical trials or in research. VIOLIN contains information for 454 vaccines or vaccine candidates for 73 pathogens. VIOLIN also contains many bioinformatics tools for vaccine data analysis, data integration, and vaccine target prediction. To demonstrate the applicability of VIOLIN for vaccine research, VIOLIN was used for bioinformatics analysis of existing Brucella vaccines and prediction of new Brucella vaccine targets. VIOLIN contains many literature mining programs (e.g., Vaxmesh) that provide in-depth analysis of Brucella vaccine literature. As a result of manual literature curation, VIOLIN contains information for 38 Brucella vaccines or vaccine candidates, 14 protective Brucella antigens, and 68 host response studies to Brucella vaccines from 97 peer-reviewed articles. These Brucella vaccines are classified in the Vaccine Ontology (VO) system and used for different ontological applications. The web-based VIOLIN vaccine target prediction program Vaxign was used to predict new Brucella vaccine targets. Vaxign identified 14 outer membrane proteins that are conserved in six virulent strains from B. abortus, B. melitensis, and B. suis that are pathogenic in humans. Of the 14 membrane proteins, two proteins (Omp2b and Omp31-1) are not present in B. ovis, a Brucella species that is not pathogenic in humans. Brucella vaccine data stored in VIOLIN were compared and analyzed using the VIOLIN query system. Bioinformatics curation and ontological representation of Brucella vaccines
Mahmoud, Mohammed Bashir
The acquired immunodeficiency syndrome (AIDS) has impacted the civilized world like no other disease. This research aimed to discuss some of the main aids-related complications and their detection by radiology tests, specifically central nervous system and musculoskeletal system disorders. The objectives are: to show specific characteristics of various diseases of HIV patient, to analyze the effect of pathology in patients by radiology, to enhance the knowledge of technologists in aids imaging and to improve communication skills between patient and radiology technologists
Ijsselmuiden, C; Evian, C; Matjilla, J; Steinberg, M; Schneider, H
The National AIDS Convention in South Africa (NACOSA) in October 1992 was the first real attempt to address HIV/AIDS. In Soweto, government, the African National Congress, nongovernmental organizations, and organized industry and labor representatives worked for 2 days to develop a national plan of action, but it did not result in a united effort to fight AIDS. The highest HIV infection rates in South Africa are among the KwaZulu in Natal, yet the Inkatha Freedom Party did not attend NACOSA. This episode exemplifies the key obstacles for South Africa to prevent and control AIDS. Inequality of access to health care may explain why health workers did not diagnose the first AIDS case in blacks until 1985. Migrant labor, Bantu education, and uprooted communities affect the epidemiology of HIV infection. Further, political and social polarization between blacks and whites contributes to a mindset that AIDS is limited to the other race which only diminishes the personal and collective sense of susceptibility and the volition and aptitude to act. The Department of National Health and Population Development's voluntary register of anonymously reported cases of AIDS specifies 1517 cumulative AIDS cases (October 1992), but this number is low. Seroprevalence studies show between 400,000-450,000 HIV positive cases. Public hospitals cannot give AIDS patients AZT and DDI. Few communities provided community-based care. Not all hospitals honor confidentiality and patients' need for autonomy. Even though HIV testing is not mandatory, it is required sometimes, e.g., HIV testing of immigrants. AIDS Training, Information and Counselling Centers are in urban areas, but not in poor areas where the need is most acute. The government just recently developed in AIDS education package for schools, but too many people consider it improper, so it is not being used. The poor quality education provided blacks would make it useless anyhow. Lifting of the academic boycott will allow South African
Lu, Shan; Wang, Shixia
Biodefense vaccines are developed against a diverse group of pathogens. Vaccines were developed for some of these pathogens a long time ago but they are facing new challenges to move beyond the old manufacturing technologies. New vaccines to be developed against other pathogens have to determine whether to follow traditional vaccination strategies or to seek new approaches. Advances in basic immunology and recombinant DNA technology have fundamentally transformed the process of formulating a vaccine concept, optimizing protective antigens, and selecting the most effective vaccine delivery approach for candidate biodefense vaccines. PMID:19837293
Arndt, Channing; Jones, Edward Samuel; Tarp, Finn
The micro-macro paradox has been revived. Despite broadly positive evaluations at the micro- and meso-levels, recent literature doubts the ability of foreign aid to foster economic growth and development. This paper assesses the aid-growth literature and, taking inspiration from the program...... evaluation literature, we re-examine key hypotheses. In our findings, aid has a positive and statistically significant causal effect on growth over the long run, with confidence intervals conforming to levels suggested by growth theory. Aid remains a key tool for enhancing the development prospects of poor...
Madsen, Sara M K; Moore, Brian C J
The signal processing and fitting methods used for hearing aids have mainly been designed to optimize the intelligibility of speech. Little attention has been paid to the effectiveness of hearing aids for listening to music. Perhaps as a consequence, many hearing-aid users complain that they are not satisfied with their hearing aids when listening to music. This issue inspired the Internet-based survey presented here. The survey was designed to identify the nature and prevalence of problems associated with listening to live and reproduced music with hearing aids. Responses from 523 hearing-aid users to 21 multiple-choice questions are presented and analyzed, and the relationships between responses to questions regarding music and questions concerned with information about the respondents, their hearing aids, and their hearing loss are described. Large proportions of the respondents reported that they found their hearing aids to be helpful for listening to both live and reproduced music, although less so for the former. The survey also identified problems such as distortion, acoustic feedback, insufficient or excessive gain, unbalanced frequency response, and reduced tone quality. The results indicate that the enjoyment of listening to music with hearing aids could be improved by an increase of the input and output dynamic range, extension of the low-frequency response, and improvement of feedback cancellation and automatic gain control systems. © The Author(s) 2014.
Sara M. K. Madsen
Full Text Available The signal processing and fitting methods used for hearing aids have mainly been designed to optimize the intelligibility of speech. Little attention has been paid to the effectiveness of hearing aids for listening to music. Perhaps as a consequence, many hearing-aid users complain that they are not satisfied with their hearing aids when listening to music. This issue inspired the Internet-based survey presented here. The survey was designed to identify the nature and prevalence of problems associated with listening to live and reproduced music with hearing aids. Responses from 523 hearing-aid users to 21 multiple-choice questions are presented and analyzed, and the relationships between responses to questions regarding music and questions concerned with information about the respondents, their hearing aids, and their hearing loss are described. Large proportions of the respondents reported that they found their hearing aids to be helpful for listening to both live and reproduced music, although less so for the former. The survey also identified problems such as distortion, acoustic feedback, insufficient or excessive gain, unbalanced frequency response, and reduced tone quality. The results indicate that the enjoyment of listening to music with hearing aids could be improved by an increase of the input and output dynamic range, extension of the low-frequency response, and improvement of feedback cancellation and automatic gain control systems.
Tarp, Finn; Arndt, Channing; Jones, Edward Samuel
inputs. We take as our point of departure a growth accounting analysis and review both intended and unintended effects of aid. Mozambique has benefited from sustained aid inflows in conflict, post-conflict and reconstruction periods. In each of these phases aid has made an unambiguous, positive...... contribution both enabling and supporting rapid growth since 1992. At the same time, the proliferation of donors and aid-supported interventions has burdened local administration and there is a distinct need to develop government accountability to its own citizens rather than donor agencies. In ensuring...
evolved since World War II in response to a dramatically changing global political and economic context. I review the aid process and associated trends in the volume and distribution of aid and categorize some of the key goals, principles and institutions of the aid system. The evidence on whether aid has...... been effective in furthering economic growth and development is discussed in some detail. I add perspective and identify some critical unresolved issues. I finally turn to the current development debate and discuss some key concerns, which I believe should be kept in mind in formulating any agenda...
Tabbara, Khaled S
Leishmaniasis is a vector-born protozoan disease. Approximately 12 million individuals are affected worldwide with an estimated annual incidence of 1.5-2 million. Two clinical manifestations are recognized, cutaneous, and visceral, both of which are common in the Middle East. In both forms, infection is chronic, with potential deformities, persistence following cure, and lifelong risk of reactivation. Attempts to develop an effective human Leishmania vaccine have not yet succeeded. Leishmanization, a crude form of live vaccination historically originated in this part of the world. Experimental vaccination has been extensively studied in model animals in the past 2 decades. In this review, major human killed vaccine trials are surveyed, and modern trends in Leishmania vaccine development, including subunit vaccines, naked DNA vaccines, and transmission blocking vaccines are explored. Recent findings of a link between persistence of live parasites, and maintenance of long-term immunity suggest live vaccination with attenuated strains, as a future vaccination strategy.
Soriano, Alessandra; Nesher, Gideon; Shoenfeld, Yehuda
Vaccinations have been used as an essential tool in the fight against infectious diseases, and succeeded in improving public health. However, adverse effects, including autoimmune conditions may occur following vaccinations (autoimmune/inflammatory syndrome induced by adjuvants--ASIA syndrome). It has been postulated that autoimmunity could be triggered or enhanced by the vaccine immunogen contents, as well as by adjuvants, which are used to increase the immune reaction to the immunogen. Fortunately, vaccination-related ASIA is uncommon. Yet, by defining individuals at risk we may further limit the number of individuals developing post-vaccination ASIA. In this perspective we defined four groups of individuals who might be susceptible to develop vaccination-induced ASIA: patients with prior post-vaccination autoimmune phenomena, patients with a medical history of autoimmunity, patients with a history of allergic reactions, and individuals who are prone to develop autoimmunity (having a family history of autoimmune diseases; asymptomatic carriers of autoantibodies; carrying certain genetic profiles, etc.). Copyright © 2014 Elsevier Ltd. All rights reserved.
The study of human genetic diseases can be greatly aided by animal models because of their similarity .... and gene targeting in embryonic stem cells) has been a powerful tool in .... endonucleases that are designed to make a doublestrand.
Maksiutov, R A; Gavrilova, E V; Shchelkunov, S N
The review gives data on the history of smallpox vaccination and shows the high topicality of designing the current safe vaccines against orthopoxviruses. Four generations of live smallpox, protein subunit, and DNA vaccines are considered. Analysis of the data published leads to the conclusion that it is promising to use the up-to-date generations of safe smallpox subunit or DNA vaccines for mass primary immunization with possible further revaccination with classical live vaccine.
Andries, Oliwia; Kitada, Tasuku; Bodner, Katie; Sanders, Niek N; Weiss, Ron
Nucleic acid vaccines have been gaining attention as an alternative to the standard attenuated pathogen or protein based vaccine. However, an unrealized advantage of using such DNA or RNA based vaccination modalities is the ability to program within these nucleic acids regulatory devices that would provide an immunologist with the power to control the production of antigens and adjuvants in a desirable manner by administering small molecule drugs as chemical triggers. Advances in synthetic biology have resulted in the creation of highly predictable and modular genetic parts and devices that can be composed into synthetic gene circuits with complex behaviors. With the recent advent of modified RNA gene delivery methods and developments in the RNA replicon platform, we foresee a future in which mammalian synthetic biologists will create genetic circuits encoded exclusively on RNA. Here, we review the current repertoire of devices used in RNA synthetic biology and propose how programmable 'smart vaccines' will revolutionize the field of RNA vaccination.
Sahoo, Malaya K; Holubar, Marisa; Huang, ChunHong; Mohamed-Hadley, Alisha; Liu, Yuanyuan; Waggoner, Jesse J; Troy, Stephanie B; Garcia-Garcia, Lourdes; Ferreyra-Reyes, Leticia; Maldonado, Yvonne; Pinsky, Benjamin A
Oral poliovirus vaccine can mutate to regain neurovirulence. To date, evaluation of these mutations has been performed primarily on culture-enriched isolates by using conventional Sanger sequencing. We therefore developed a culture-independent, deep-sequencing method targeting the 5' untranslated region (UTR) and P1 genomic region to characterize vaccine-related poliovirus variants. Error analysis of the deep-sequencing method demonstrated reliable detection of poliovirus mutations at levels of vaccinated, asymptomatic children and their close contacts collected during a prospective cohort study in Veracruz, Mexico, revealed no vaccine-derived polioviruses. This was expected given that the longest duration between sequenced sample collection and the end of the most recent national immunization week was 66 days. However, we identified many low-level variants (Sabin serotypes, as well as vaccine-related viruses with multiple canonical mutations associated with phenotypic reversion present at high levels (>90%). These results suggest that monitoring emerging vaccine-related poliovirus variants by deep sequencing may aid in the poliovirus endgame and efforts to ensure global polio eradication. Copyright © 2017 Sahoo et al.
Mendel-Van Alstyne, Judith A; Nowak, Glen J; Aikin, Ann L
videos as part of vaccination education efforts. Findings can aid those developing vaccination education materials and resources designed to foster vaccine confidence. Published by Elsevier Ltd.
Full Text Available Abstract Background Varicella-zoster virus (VZV causes chickenpox in children and shingles in older people. Currently, live attenuated vaccines based on the Oka strain are available worldwide. In Korea, an attenuated VZV vaccine has been developed from a Korean isolate and has been commercially available since 1994. Despite this long history of use, the mechanism for the attenuation of the vaccine strain is still elusive. We attempted to understand the molecular basis of attenuation mechanism by full genome sequencing and comparative genomic analyses of the Korean vaccine strain SuduVax. Results SuduVax was found to contain a genome that was 124,759 bp and possessed 74 open reading frames (ORFs. SuduVax was genetically most close to Oka strains and these Korean-Japanese strains formed a strong clade in phylogenetic trees. SuduVax, similar to the Oka vaccine strains, underwent T- > C substitution at the stop codon of ORF0, resulting in a read-through mutation to code for an extended form of ORF0 protein. SuduVax also shared certain deletion and insertion mutations in ORFs 17, 29, 56 and 60 with Oka vaccine strains and some clinical strains. Conclusions The Korean VZV vaccine strain SuduVax is genetically similar to the Oka vaccine strains. Further comparative genomic and bioinformatics analyses will help to elucidate the molecular basis of the attenuation of the VZV vaccine strains.
John, T Jacob
Inactivated poliovirus vaccine (IPV), developed in the USA by Jonas Salk in the early 1950s, was field tested in 1954, and found to be safe and effective. The year 2004 marks the golden jubilee of this breakthrough. From 1955 IPV was used extensively in the US and polio incidence declined by more than 95 per cent. However, in 1962, when oral poliovirus vaccine (OPV) became available, the national policy was shifted to its exclusive use, for reasons other than science and economics. The World Health Organisation (WHO) also adopted the policy of the exclusive use of OPV in developing countries. Thus IPV fell into disrepute in much of the world, while Northern European countries continued to use it. New research led to improving its potency, reducing its manufacturing costs and combining it with the diphtheria-tetanus-pertussis (DTP) vaccine to simplify its administration and reduce programmatic costs. All countries that chose to persist with IPV eliminated poliovirus circulation without OPV-induced polio or the risk of live vaccine viruses reverting to wild-like nature. IPV is highly immunogenic, confers mucosal immunity and exerts herd protective effect, all qualities of a good vaccine. It can be used in harmony with the extendend programme on immunization (EPI) schedule of infant immunisation with DTP, thus reducing programmatic costs. During the last ten years IPV has once again regained its popularity and some 25 industrialised countries use it exclusively. The demand is increasing from other countries and the supply has not caught up, leaving market forces to dictate the sale price of IPV. Anticipating such a turn of events India had launched its own IPV manufacturing programme in 1987, but the project was closed in 1992. Today it is not clear if we can complete the job of global polio eradication without IPV, on account of the genetic instability of OPV and the consequent tendency of vaccine viruses to revert to wild-like properties. The option to use IPV is
Hansen, M; Met, Ö; Svane, I M
Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor...... to transiently affect in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....
Martínez-Vega, Ruth Aralí; Carrasquila, Gabriel; Luna, Expedito; Ramos-Castañeda, José
The vaccine against Dengue virus (DENV), Dengvaxia® (CYD), produced by Sanofi-Pasteur, has been registered by several national regulatory agencies; nevertheless, the performance and security of this vaccine have been challenged in a series of recent papers. In this work, we intend to contribute to the debate by analyzing the concept of an enhancing vaccine, presenting objections to the epidemiological model base of the concept and, likewise, presenting data that contradict that concept. Copyright © 2017 Elsevier Ltd. All rights reserved.
Roč. 20, č. 1 (2002), s. 207-212 ISSN 1019-6439 Institutional research plan: CEZ:AV0Z5052915 Keywords : human papilloma viruses * tumour vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.931, year: 2002
Genetically modified soya beans provide a scalable, low-cost method of producing microbicides that prevent AIDS, a technique sustainable for resource-poor countries where AIDS is spreading rapidly. According to the Joint United Nations Programme on HIV/AIDS, more than 36 million people worldwide are living with HIV. While the number of AIDS-related deaths are decreasing, infection rates are still increasing, specifically in Eastern and Southern Africa.
Evans, Jennifer S; Horton, Daniel L; Easton, Andrew J; Fooks, Anthony R; Banyard, Ashley C
All members of the lyssavirus genus are capable of causing disease that invariably results in death following the development of clinical symptoms. The recent detection of several novel lyssavirus species across the globe, in different animal species, has demonstrated that the lyssavirus genus contains a greater degree of genetic and antigenic variation than previously suspected. The divergence of species within the genus has led to a differentiation of lyssavirus isolates based on both antigenic and genetic data into two, and potentially a third phylogroup. Critically, from both a human and animal health perspective, current rabies vaccines appear able to protect against lyssaviruses classified within phylogroup I. However no protection is afforded against phylogroup II viruses or other more divergent viruses. Here we review current knowledge regarding the diversity and antigenicity of the lyssavirus glycoprotein. We review the degree of cross protection afforded by rabies vaccines, the genetic and antigenic divergence of the lyssaviruses and potential mechanisms for the development of novel lyssavirus vaccines for use in areas where divergent lyssaviruses are known to circulate, as well as for use by those at occupational risk from these pathogens. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.
9 avr. 2018 ... Les vaccins actuels contre la cowdriose ne sont pas très efficaces car ils protègent seulement contre un seul génotype, mais bon nombre de souches de la maladie peuvent être présentes dans la même zone. Quant aux vaccins contre la PPCC, ils sont produits à l'aide de cultures de la bactérie Mccp et ...
Rahmani, Fouad Lazhar
The aim of this paper is to present mathematical modelling of the spread of infection in the context of the transmission of the human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS). These models are based in part on the models suggested in the field of th AIDS mathematical modelling as reported by ISHAM .
Addison, Tony; Morrissey, Oliver; Tarp, Finn
This Special Issue explores macroeconomic effects of aid from various perspectives through a blend of studies, both conceptual and empirical in nature. The overall aim is to enhance the understanding of the macroeconomic dimensions of aid in the policy and research communities, and to inspire...
Pohl, Melvin I.
After defining HIV and the AIDS disease and outlining symptoms and means of infection, this fact sheet lists the ways alcohol and drugs are involved with the AIDS epidemic, noting that needle-sharing transmits the virus; that alcohol or mood-altering drugs like crack cocaine cause disinhibition, increase sex drive, encourage sex for drugs, and…
Jones, Edward Samuel
of data spanning nearly 50 years, this paper uses panel cointegration techniques to consider these issues. The analysis provides clear evidence for heterogeneity both between donors and over time, bandwagon effects, and a growing influence of security considerations in aid provision. Domestic...... macroeconomic shocks have a moderate but delayed effect on aid disbursements....
Huddleston, Thomas, Jr.; Batty, Burt F.
Student financial assistance services are becoming a major part of the institutional marketing plan as traditional college-age students decline in numbers and price competition among institutions increases. The effect of financial aid on enrollment and admissions processes is discussed along with the role of the financial aid officer. (Author/LBH)
Lof, Matthijs; Mekasha, Tseday Jemaneh; Tarp, Finn
to nonrandom omission of a large proportion of observations. Furthermore, we show that NDHKM’s use of co-integrated regressions is not a suitable empirical strategy for estimating the causal effect of aid on income. Evidence from a Panel VAR model estimated on the dataset of NDHKM, suggests a positive...... and statistically significant long-run effect of aid on income....
Doucouliagos, Hristos; Paldam, Martin
The AEL consists of empirical macro studies of the effects of development aid. At the end of 2004 it had reached 97 studies of three families, which we have summarized in one study each using meta-analysis. Studies of the effect on investments show that they rise by 1/3 of the aid – the rest is c...
Danchin, M H; Costa-Pinto, J; Attwell, K; Willaby, H; Wiley, K; Hoq, M; Leask, J; Perrett, K P; O'Keefe, Jacinta; Giles, M L; Marshall, H
Maternal and childhood vaccine decision-making begins prenatally. Amongst pregnant Australian women we aimed to ascertain vaccine information received, maternal immunisation uptake and attitudes and concerns regarding childhood vaccination. We also aimed to determine any correlation between a) intentions and concerns regarding childhood vaccination, (b) concerns about pregnancy vaccination, (c) socioeconomic status (SES) and (d) uptake of influenza and pertussis vaccines during pregnancy and routine vaccines during childhood. Women attending public antenatal clinics were recruited in three Australian states. Surveys were completed on iPads. Follow-up phone surveys were done three to six months post delivery, and infant vaccination status obtained via the Australian Childhood Immunisation Register (ACIR). Between October 2015 and March 2016, 975 (82%) of 1184 mothers consented and 406 (42%) agreed to a follow up survey, post delivery. First-time mothers (445; 49%) had significantly more vaccine concerns in pregnancy and only 73% had made a decision about childhood vaccination compared to 89% of mothers with existing children (p-valuepost delivery survey, 46% and 82% of mothers reported receiving pregnancy influenza and pertussis vaccines respectively. The mother's degree of vaccine hesitancy and two attitudinal factors were correlated with vaccine uptake post delivery. There was no association between reported maternal vaccine uptake or SES and childhood vaccine uptake. First time mothers are more vaccine hesitant and undecided about childhood vaccination, and only two thirds of all mothers believed they received enough information during pregnancy. New interventions to improve both education and communication on childhood and maternal vaccines, delivered by midwives and obstetricians in the Australian public hospital system, may reduce vaccine hesitancy for all mothers in pregnancy and post delivery, particularly first-time mothers. Copyright © 2017 Elsevier Ltd
Grace C. Huerta
Full Text Available The world has been challenged by the AIDS epidemic for 15 years. In 1985, the U.S. Department of Health and Human Services, Centers for Disease Control, allocated funds to all state departments of education to assist schools in the development of AIDS education policies and programs. Yet, these policies do not ensure that all students receive effective AIDS education. On September 21, 1991, the Arizona Legislature passed Senate Bill 1396, which requires public schools to annually provide AIDS education in grades K-12. The bill was rescinded in 1995. With prohibitive curriculum guidelines, limited teacher training opportunities and tremendous instructional demands, this educational policy was implemented in disparate forms. By examining the perspectives of the Arizona educators (representing three school districts, this qualitative study reveals how teachers ultimately controlled the delivery and nature of AIDS instruction based upon personal values, views of teacher roles, and their interpretation of the mandate itself.
Moradian, M.A.; Chow, M.P.; Osborne, R.L.; Jenkins, M.A.
The Westinghouse Turbine Artificial Intelligence Diagnostics system or TurbinAID, can diagnose both thermodynamic and mechanical component anomalies within the turbine, and around the turbine cycle. any monitoring system can detect that a variable is in an abnormal state, but TurbinAID can also indicate the cause, and provide recommended corrective action(s). The TurbinAID Expert Systems utilize multiple sensor and variable inputs, and their interdependencies in the generation of a diagnosis. The system performs sensor validation as part of the data acquisition scheme. The TurbinAID system has been in operation for several years. This paper describes the monitoring and diagnostic functions provided by TurbinAID, and how the utility industry both nuclear and fossil, can utilize the system to enhance unit operation
... factors for developing them, such as taking oral contraceptives . A safety review of Gardasil in Denmark and ... and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark ...
... containing preservative that is added to vials of vaccine that contain more than one dose to prevent contamination and growth of potentially harmful bacteria. For children with a prior history of allergic reactions to any of these substances ...
At a special meeting held in October 1987, the World Health Organization called for a concerted, international response to acquired immunodeficiency syndrome (AIDS). Announced was the creation of a WHO Global Commission on AIDS comprised of experts in health, social, economic, legal, ethical, and biomedical fields who will advise WHO officials of developments in various aspects of the disease. Member States were united in terms of the need for open communication and support of WHO efforts to combat AIDS. By December 1987, 129 countries had reported 73,747 AIDS cases to WHO and another 3 million new cases are likely to develop by 1982. The WHO strategy is based on several concepts: 1) even in the absence of a vaccine, AIDS is controllable through widespread education; 2) longterm commitment to eradication is necessary; 3) AIDS prevention and control must be integrated into national health systems; and 4) international cooperation, coordination, and leadership is vital. National AIDS committees have been established in over 100 countries.
Fiona J. Baird
Full Text Available Traditional prophylactic vaccination to prevent illness is the primary objective of many research activities worldwide. The golden age of vaccination began with an approach called variolation in ancient China and the evolution of vaccines still continues today with modern developments such as the production of Gardasil™ against HPV and cervical cancer. The historical aspect of how different forms of vaccination have changed the face of medicine and communities is important as it dictates our future approaches on both a local and global scale. From the eradication of smallpox to the use of an experimental vaccine to save a species, this review will explore these successes in infectious disease vaccination and also discuss a few significant failures which have hampered our efforts to eradicate certain diseases. The second part of the review will explore designing a prophylactic vaccine for the growing global health concern that is allergy. Allergies are an emerging global health burden. Of particular concern is the rise of food allergies in developed countries where 1 in 10 children is currently affected. The formation of an allergic response results from the recognition of a foreign component by our immune system that is usually encountered on a regular basis. This may be a dust-mite or a prawn but this inappropriate immune response can result in a life-time of food avoidance and lifestyle restrictions. These foreign components are very similar to antigens derived from infectious pathogens. The question arises: should the allergy community be focussing on protective measures rather than ongoing therapeutic interventions to deal with these chronic inflammatory conditions? We will explore the difficulties and benefits of prophylactic vaccination against various allergens by means of genetic technology that will dictate how vaccination against allergens could be utilised in the near future.
Salmona, Maud; Gazaignes, Sandrine; Mercier-Delarue, Severine; Garnier, Fabienne; Korimbocus, Jehanara; Colin de Verdière, Nathalie; LeGoff, Jerome; Roques, Pierre; Simon, François
The worldwide use of yellow fever (YF) live attenuated vaccines came recently under close scrutiny as rare but serious adverse events have been reported. The population identified at major risk for these safety issues were extreme ages and immunocompromised subjects. Study NCT01426243 conducted by the French National Agency for AIDS research is an ongoing interventional study to evaluate the safety of the vaccine and the specific immune responses in HIV-infected patients following 17D-204 vaccination. As a preliminary study, we characterized the molecular diversity from E gene of the single 17D-204 vaccine batch used in this clinical study. Eight vials of lyophilized 17D-204 vaccine (Stamaril, Sanofi-Pasteur, Lyon, France) of the E5499 batch were reconstituted for viral quantification, cloning and sequencing of C/prM/E region. The average rate of virions per vial was 8.68 ± 0.07 log₁₀ genome equivalents with a low coefficient of variation (0.81%). 246 sequences of the C/prM/E region (29-33 per vials) were generated and analyzed for the eight vials, 25 (10%) being defective and excluded from analyses. 95% of sequences had at least one nucleotide mutation. The mutations were observed on 662 variant sites distributed through all over the 1995 nucleotides sequence and were mainly non-synonymous (66%). Genome variability between vaccine vials was highly homogeneous with a nucleotide distance ranging from 0.29% to 0.41%. Average p-distances observed for each vial were also homogeneous, ranging from 0.15% to 0.31%. This study showed a homogenous YF virus RNA quantity in vaccine vials within a single lot and a low clonal diversity inter and intra vaccine vials. These results are consistent with a recent study showing that the main mechanism of attenuation resulted in the loss of diversity in the YF virus quasi-species. Copyright © 2015 Elsevier Ltd. All rights reserved.
Ogai, N; Nonaka, I; Toda, Y; Ono, T; Minegishi, S; Inou, A; Hachiya, M; Fukamizu, H
The intradermal (ID) route for vaccination represents an effective alternative to subcutaneous (SC)/intramuscular administration to induce protective immunity. However, a critical issue associated with ID vaccination is the precise delivery of solution in the upper dermis, which ensures enhanced immunity. We fabricated a hollow microneedle unit made of poly-glycolic acid by injection molding and bonding, and created a dedicated prototype injector. To ensure ID delivery of solution, the injected site was macroscopically and microscopically examined. Serum immunoglobulin G antibody production was measured by enzyme immunoassay and compared in groups of rats following either ID delivery with microneedles or SC administration with a 27-G stainless needle of graded vaccine doses. The unit used a tandem array of six microneedles, each with a side delivery hole, and a conduit inside for solution. Microneedles installed in the injector punctured the skin with the aid of a spring. Injection of solution formed a wheal due to ID distribution. Histologically, a wedge-shaped skin defect in the upper skin corresponded to each puncture site. Antibody titers following vaccinations on days 1 and 8 were significantly higher with ID injection than with SC delivery on day 15 and every 7 days thereafter until day 36 with mumps vaccination, and until day 36 with varicella vaccination. The microneedle unit presented here delivered solution intradermally without any difficulty and evoked antibody responses against viruses even with the reduced vaccine volume. Our findings confirm promising results of ID delivery as an immunogenic option to enhance vaccination efficacy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Wang, Ching-Min; Chen, Shou-Chien; Chen, Kow-Tong
Rotaviruses remain the major cause of childhood diarrheal disease worldwide and of diarrheal deaths of infants and children in developing countries. The huge burden of childhood rotavirus-related diarrhea in the world continues to drive the remarkable pace of vaccine development. Research articles were searched using terms "rotavirus" and "rotavirus vaccine" in MEDLINE and PubMed. Articles not published in the English language, articles without abstracts, and opinion articles were excluded from the review. After preliminary screening, all articles were reviewed and synthesized to provide an overview of current vaccines and vaccination programs. In this review of the global rotavirus vaccines and vaccination programs, the principles of rotavirus vaccine development and the efficacy of the currently licensed vaccines from both developed and developing countries were summarized. Rotavirus is a common cause of diarrhea in children in both developed and developing countries. Rotavirus vaccination is a cost-effective measure to prevent rotavirus diarrhea.
Worz, Chad; Martin, Caren McHenry; Travis, Catherine
Several vaccine-preventable diseases-influenza, pneumonia, herpes zoster, and pertussis-threaten the health of older adults in the United States. Both the costs associated with treating these diseases and the potential to increase morbidity and mortality are high for this patient population. Pharmacists and other health care professionals play a significant role in ensuring the elderly patient receives the recommended vaccines at the recommended intervals.
This photo was taken in the village of Ladji, which is on the outskirts of Cotonou, the capital of Benin. At the time, I was a second year medical student volunteering at a local medical clinic. On every Wednesday morning, many Beninese babies, like this one, cry out of discomfort while receiving their monthly vaccinations. The photo shows a local clinic nurse administering the vaccination.
Full Text Available This photo was taken in the village of Ladji, which is on the outskirts of Cotonou, the capital of Benin. At the time, I was a second year medical student volunteering at a local medical clinic. On every Wednesday morning, many Beninese babies, like this one, cry out of discomfort while receiving their monthly vaccinations. The photo shows a local clinic nurse administering the vaccination.
Wang, Lui; Bayer, Steven E.
Genetic algorithms are mathematical, highly parallel, adaptive search procedures (i.e., problem solving methods) based loosely on the processes of natural genetics and Darwinian survival of the fittest. Basic genetic algorithms concepts are introduced, genetic algorithm applications are introduced, and results are presented from a project to develop a software tool that will enable the widespread use of genetic algorithm technology.
Nicol, A F; Andrade, C V; Russomano, F B; Rodrigues, L L S; Oliveira, N S; Provance, D W
Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.
Full Text Available Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.