Immunopotentiating reconstituted influenza virus virosome vaccine delivery system for immunization against hepatitis A.
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Hepatitis A virus (HAV) was purified from MRC-5 human diploid cell cultures, inactivated with formalin, and evaluated for safety and immunogenicity in humans. Three vaccine formulations were produced: (a) a fluid preparation containing inactivated HAV, (b) inactivated HAV adsorbed to Al(OH)3, and (c) inactivated HAV coupled to novel immunopotentiating reconstituted influenza virosomes (IRIV). IRIV were prepared by combining phosphatidylcholine, phosphatidylethanolamine, phospholipids originating from the influenza virus envelope, influenza virus hemagglutinin, and neuraminidase. The HAV-IRIV appeared as unilamellar vesicles with a diameter of approximately 150 nm when viewed by transmission electron microscopy. Upon intramuscular injection, the alum-adsorbed vaccine was associated with significantly (P < 0.01) more local adverse reactions than either the fluid or IRIV formulations. 14 d after a single dose of vaccine, all the recipients of the IRIV formulation seroconverted (> or = 20 mIU/ml) versus 30 and 44% for those who received the fluid and alum-adsorbed vaccines, respectively (P < 0.001). The geometric mean anti-HAV antibody titer achieved after immunization with the IRIV-HAV vaccine was also significantly higher (P < 0.005) compared with the other two vaccines. (+info)
A six-year survey of immunogenicity and efficacy of hepatitis B vaccine in infants born to HBsAg carriers.
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Although the efficacy of hepatitis B vaccine is well documented, the duration of immunity of healthy infants after vaccination is unknown. 99 infants born to hepatitis B surface antigen (HBsAg)-carrier mothers were studied and found to have positive anti-HBs (titer: greater than or equal to 10 mIU/mL) after a first injection of vaccine at the ages of 1 to 6 years. The infants were randomly divided into four groups of recipients treated with the vaccine of the National Institute of Allergy and Infectious Diseases (NIAID), U.S.A. or that of the Beijing Biological Products Research Institute (BBPRI), BBPRI vaccine in combination with hepatitis B immune globulin (HBIG) and placebo. The results showed that the protective efficacy dropped considerably after 5 years with NIAID vaccine, after 3 years with BBPRI vaccine and after 4 years with BBPRI vaccine plus HBIG. This suggests that a booster injection is needed 5 years after the first injection of NIAID vaccine, 3 years after BBPRI vaccine, and 4 years after BBPRI vaccine plus HBIG. (+info)
Optimal induction of T-cell responses against hepatitis C virus E2 by antigen engineering in DNA immunization.
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Although DNA immunization is a safe and efficient method for inducing cellular immune responses, it generates relatively weak and slow immune responses. Here, we investigated the effect of hepatitis C virus (HCV) antigen modifications on the induction of T-cell responses in DNA immunization. It is likely that the strength of T-cell responses has an inverse relationship with the length of the insert DNA. Interestingly, a mixture of several plasmids carrying each gene induced a higher level of T-cell responses than a single plasmid expressing a long polyprotein. Moreover, the presence of a transmembrane domain in HCV E2 resulted in stronger T-cell responses against E2 protein than its absence. Taken together, our results indicate that the tailored modifications of DNA-encoded antigens are capable of optimizing the induction of T-cell responses which is required for eliminating the cells chronically infected with highly variable viruses such as HCV and human immunodeficiency virus. (+info)
An economic assessment of pre-vaccination screening for hepatitis A and B.
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OBJECTIVE: The availability of a single vaccine active against hepatitis A and B may facilitate prevention of both infections, but complicates the question of whether to conduct pre-vaccination screening. The authors examined the cost-effectiveness of pre-vaccination screening for several populations: first-year college students, military recruits, travelers to hepatitis A-endemic areas, patients at sexually transmitted disease clinics, and prison inmates. METHODS: Three prevention protocols were examined: (1) screen and defer vaccination until serology results are known; (2) screen and begin vaccination immediately to avoid a missed vaccination opportunity; and (3) vaccinate without screening. Data describing pre-vaccination immunity, vaccine effectiveness, and prevention costs borne by the health system (i.e., serology, vaccine acquisition, and administration) were derived from published literature and U.S. government websites. Using spreadsheet models, the authors calculated the ratio of prevention costs to the number of vaccine protections conferred. RESULTS: The vaccinate without screening protocol was most cost-effective in nine of 10 analyses conducted under baseline assumptions, and in 69 of 80 sensitivity analyses. In each population considered, vaccinate without screening was less costly than and at least equally as effective as screen and begin vaccination. The screen and defer vaccination protocol would reduce costs in seven populations, but effectiveness would also be lower. CONCLUSIONS: Unless directed at vaccination candidates with the highest probability of immunity, pre-vaccination screening for hepatitis A and B immunity is not cost-effective. Balancing cost reduction with reduced effectiveness, screen and defer may be preferred for older travelers and prison inmates. (+info)
DNA vaccination protects mice against challenge with Listeria monocytogenes expressing the hepatitis C virus NS3 protein.
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The goal of this study was to develop a new surrogate challenge model for use in evaluating protective cell-mediated immune responses against hepatitis C virus (HCV) antigens. The use of recombinant Listeria monocytogenes organisms which express HCV antigens provides novel tools with which to assay such in vivo protection, as expression of immunity against this hepatotropic bacterial pathogen is dependent on antigen-specific CD8(+) T lymphocytes. A plasmid DNA vaccine encoding a ubiquitin-NS3 fusion protein was generated, and its efficacy was confirmed by in vivo induction of NS3-specific, gamma interferon-secreting T cells following vaccination of BALB/c mice. These immunized mice also exhibited specific in vivo protection against subsequent challenge with a recombinant L. monocytogenes strain (TC-LNS3) expressing the NS3 protein. Notably, sublethal infection of naive mice with strain TC-LNS3 induced similar NS3-specific T-cell responses. These findings suggest that recombinant strains of L. monocytogenes expressing HCV antigens should prove useful for evaluating, or even inducing, protective immune responses against HCV antigens. (+info)
Recent advances in DNA vaccine of hepatitis virus.
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Nucleic acid vaccine or DNA vaccine is a hopeful vaccine to prevent and treat viral hepatitis. Problems exist in different DNA vaccines for HBV or HCV. Optimal animal model should be established study vaccine against hepatitis. Apart from the strategy to enhance the efficiency of DNA vaccine, combined use of cytokines or chemokines, different routes of inoculation, design of optimal vector, ISS insertion in the plasmid vectors, etc to enhance the efficiency of DNA vaccine are reviewed. (+info)
Varied immunity generated in mice by DNA vaccines with large and small hepatitis delta antigens.
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Whether the hepatitis delta virus (HDV) DNA vaccine can induce anti-HDV antibodies has been debatable. The role of the isoprenylated motif of hepatitis delta antigens (HDAg) in the generation of immune responses following DNA-based immunization has never been studied. Plasmids p2577L, encoding large HDAg (L-HDAg), p2577S, expressing small HDAg (S-HDAg), and p25L-211S, encoding a mutant form of L-HDAg with a cysteine-to-serine mutation at codon 211, were constructed in this study. Mice were intramuscularly injected with the plasmids. The anti-HDV antibody titers, T-cell proliferation responses, T-helper responses, and HDV-specific, gamma interferon (IFN-gamma)-producing CD8(+) T cells were analyzed. Animals immunized with p2577S showed a strong anti-HDV antibody response. Conversely, only a low titer of anti-HDV antibodies was detected in mice immunized with p2577L. Epitope mapping revealed that the anti-HDV antibodies generated by p2577L vaccination hardly reacted with epitope amino acids 174 to 194, located at the C terminus of S-HDAg. All of the HDAg-encoding plasmids could induce significant T-cell proliferation responses and generate Th1 responses and HDV-specific, IFN-gamma-producing CD8(+) T cells. In conclusion, HDAg-specific antibodies definitely exist following DNA vaccination. The magnitudes of the humoral immune responses generated by L-HDAg- and S-HDAg-encoding DNA vaccines are different. The isoprenylated motif can mask epitope amino acids 174 to 195 of HDAg but does not interfere with cellular immunity following DNA-based immunization. These findings are important for the choice of a candidate HDV DNA vaccine in the future. (+info)
Control of heterologous hepatitis C virus infection in chimpanzees is associated with the quality of vaccine-induced peripheral T-helper immune response.
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Prophylactic hepatitis C virus (HCV) vaccine trials with human volunteers are pending. There is an important need for immunological end points which correlate with vaccine efficacy and which do not involve invasive procedures, such as liver biopsies. By using a multicomponent DNA priming-protein boosting vaccine strategy, naive chimpanzees were immunized against HCV structural proteins (core, E1, and E2) as well as a nonstructural (NS3) protein. Following immunization, exposure to the heterologous HCV 1b J4 subtype resulted in a peak of plasma viremia which was lower in both immunized animals. Compared to the naive infection control and nine additional historical controls which became chronic, vaccinee 2 (Vac2) rapidly resolved the infection, while the other (Vac1) clearly controlled HCV infection. Immunization induced antibodies, peptide-specific gamma interferon (IFN-gamma), protein-specific lymphoproliferative responses, IFN-gamma, interleukin-2 (IL-2), and IL-4 T-helper responses in both vaccinees. However, the specificities were markedly different: Vac2 developed responses which were lower in magnitude than those of Vac1 but which were biased towards Th1-type cytokine responses for E1 and NS3. This proof-of-principle study in chimpanzees revealed that immunization with a combination of nonstructural and structural antigens elicited T-cell responses associated with an alteration of the course of infection. Our findings provide data to support the concept that the quality of the response to conserved epitopes and the specific nature of the peripheral T-helper immune response are likely pivotal factors influencing the control and clearance of HCV infection. (+info)