Protective immunity against murine hepatitis virus (MHV) induced by intranasal or subcutaneous administration of hybrids of tobacco mosaic virus that carries an MHV epitope.
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Hybrids of tobacco mosaic virus (TMV) were constructed with the use of fusion to the coat protein peptides of 10 or 15 amino acids, containing the 5B19 epitope from the spike protein of murine hepatitis virus (MHV) and giving rise to TMV-5B19 and TMV-5B19L, respectively. The TMV hybrids were propagated in tobacco plants, and the virus particles were purified. Immunogold labeling, with the use of the monoclonal MAb5B19 antibody, showed specific decoration of hybrid TMV particles, confirming the expression and display of the MHV epitope on the surface of the TMV. Mice were immunized with purified hybrid viruses after several regimens of immunization. Mice that received TMV-5B19L intranasally developed serum IgG and IgA specific for the 5B19 epitope and for the TMV coat protein. Hybrid TMV-5B19, administered by subcutaneous injections, elicited high titers of serum IgG that was specific for the 5B19 epitope and for coat protein, but IgA that was specific against 5B19 was not observed. Mice that were immunized with hybrid virus by subcutaneous or intranasal routes of administration survived challenge with a lethal dose (10 x LD50) of MHV strain JHM, whereas mice administered wild-type TMV died 10 d post challenge. Furthermore, there was a positive correlation between the dose of administered immunogen and protection against MHV infection. These studies show that TMV can be an effective vaccine delivery vehicle for parenteral and mucosal immunization and for protection from challenge with viral infection. (+info)
Expression of noncovalent hepatitis C virus envelope E1-E2 complexes is not required for the induction of antibodies with neutralizing properties following DNA immunization.
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Interactive glycoproteins present on the surface of viral particles represent the main target of neutralizing antibodies. The ability of DNA vaccination to induce antibodies directed at such structures was investigated by using eight different expression plasmids engineered either to favor or to prevent interaction between the hepatitis C virus (HCV) envelope glycoproteins E1 and E2. Independently of the injection route (intramuscular or intraepidermal), plasmids expressing antigens capable of forming heterodimers presumed to be the prebudding form of the HCV envelope protein complex failed to induce any significant, stable antibodies following injection in mice. In sharp contrast, high titers of antibodies directed at both conformational and linear determinants were induced by using plasmids expressing severely truncated antigens that have lost the ability to form native complexes. In addition, only a truncated form of E2 induced antibodies reacting against the hypervariable region 1 of E2 (specifically with the C-terminal part of it) known to contain a neutralization site. When injected intraepidermally into small primates, the truncated E2-encoding plasmid induced antibodies able to neutralize in vitro the binding of a purified E2 protein onto susceptible cells. Because such antibodies have been associated with viral clearance in both humans and chimpanzees, these findings may have important implications for the development of protective immunity against HCV. (+info)
Prevention of hepatitis A through active or passive immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP).
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Routine vaccination of children is the most effective way to reduce hepatitis A incidence nationwide over time. Since licensure of hepatitis A vaccine in 1995, this strategy has been implemented incrementally, starting with the recommendation of the Advisory Committee on Immunization Practices (ACIP) in 1996 to vaccinate children living in communities with the highest rates of infection and disease. These updated recommendations represent the next phase of this hepatitis A immunization strategy. Vaccination of children living in states and communities with consistently elevated rates of hepatitis A will provide protection from disease and is expected to reduce the overall incidence of hepatitis A. This report updates the ACIP's 1996 recommendations on the prevention of hepatitis A through immunization (MMWR 1996;45:[No. RR-151) and includes a) new data about the epidemiology of hepatitis A; b) recent findings about the effectiveness of community-based hepatitis A vaccination programs; and c) recommendations for the routine vaccination of children in states, counties, and communities with rates that are twice the 1987-1997 national average or greater (i.e., > or = 20 cases per 100,000 population) and consideration of routine vaccination of children in states, counties, and communities with rates exceeding the 1987-1997 national average (i.e., > or = 10 but <20 cases per 100,000 population). Unchanged in this report are previous recommendations regarding the vaccination of persons in groups at increased risk for hepatitis A or its adverse consequences and recommendations regarding the use of immune globulin for protection against hepatitis A. (+info)
Immunogenicity and safety of hepatitis A vaccine in liver and renal transplant recipients.
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Organ transplant recipients with chronic hepatitis B or hepatitis C virus infection may be at increased risk of fulminant hepatitis A. Liver transplant (LTX) recipients, renal transplant (RTX) recipients, and healthy controls received 2 doses of hepatitis A vaccine 6 months apart. Anti-hepatitis A virus (anti-HAV) seroconversion after the primary dose occurred in 41% of the LTX patients, 24% of the RTX patients, and 90% of the controls. After the booster dose, the respective rates were 97%, 72%, and 100% (P<.001). RTX patients also had significantly lower geometric mean titers (GMTs) of anti-HAV than LTX patients and controls. In the RTX group, the seroconversion rate and GMT were inversely associated with the number of immunosuppressive drugs received by the patients. The vaccine was well tolerated. Hepatitis A vaccine can be recommended to LTX and RTX patients, but the patients should receive a full course of 2 doses before imminent exposure. (+info)
Interference of antibody production to hepatitis B surface antigen in a combination hepatitis A/hepatitis B vaccine.
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A randomized trial comparing 3 manufacturing consistency lots of a combination hepatitis A/hepatitis B vaccine to each other and to hepatitis A vaccine and hepatitis B vaccine given separately and concurrently was done to evaluate safety, tolerability, and immunogenicity. Healthy volunteers >/=11 years of age were divided into 4 groups. Each of 3 groups received a separate consistency lot of the combination vaccine, and 1 group received separate but concurrent injections of hepatitis A and hepatitis B vaccines. Injections were given at weeks 0 and 24. The combination vaccine was generally well tolerated. The hepatitis A portion of the combination vaccine produced clinically acceptable high seropositivity rates 4 and 52 weeks after the first injection. The hepatitis B portion of the vaccine did not produce clinically acceptable seropositivity rates 4 weeks after the second injection. Lack of antibody production may be attributed, at least in part, to immunologic interference. (+info)
Inactivated hepatitis A vaccine in Chinese patients with chronic hepatitis B infection.
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BACKGROUND: Hepatitis B (HBV)-infected patients have a higher morbidity and mortality when super-infected by hepatitis A (HAV). AIM: To evaluate the immunogenicity and safety of a commercial inactivated HAV vaccine in Chinese patients with chronic HBV infection. METHODS: Sixty-five HBV-infected patients (30 carriers, 22 chronic hepatitis, 13 cirrhosis), who were seronegative for HAV, received a dose of 1440 ELISA units of HAV vaccine at weeks 0 and 24. Twenty-eight healthy individuals aged 18-57 years, who were seronegative for both HBV and HAV infection, also received the same vaccination regimen. Seroconversion was defined as an anti-HAV titre >/= 33 mIU/mL. RESULTS: The seroconversion rates for the HBV-infected patients at weeks 2, 4 and 24 were 72, 91 and 80%, respectively. The corresponding geometric mean titres (GMTs) were 103, 311 and 123 mIU/mL. In the healthy control group the seroconversion rates were 86, 93 and 89% at weeks 2, 4 and 24. The corresponding GMTs were 112, 158 and 250 mIU/mL. There was no difference in the seroconversion rates between the two groups, but healthy controls had a significantly higher GMT at week 24 (P=0.04). Side-effects were more common in HBV patients. CONCLUSION: The HAV vaccine is equally efficacious in patients with chronic HBV infection. (+info)
Immune responses to hepatitis C virus structural and nonstructural proteins induced by plasmid DNA immunizations.
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DNA-based immunizations have been used to elicit cellular immunity to hepatitis C virus (HCV) proteins in mice. Mice were immunized by intramuscular or intradermal injections of plasmid DNA derived from a near-full-length HCV genotype 1b genomic clone (pRC/B2) or individual genomic clones. These immunizations induced cytotoxic T lymphocytes (CTLs), as revealed in standard chromium-release assays that used syngeneic peptide-pulsed or transfected target cells. These assays identified four CTL epitopes within the capsid, E1, and E2 regions of the polyprotein sequence of HCV genotype 1a that were cross-reactive with HCV genotype 1b. Additionally, CTLs derived from mice immunized with either NS3 or NS5 specifically lysed target cells sensitized to either the genotype 1a or 1b gene products. Nucleic acid immunizations also generated humoral immunity to HCV proteins, as detected by anti-HCV reactivity to NS3 and capsid in ELISAs and immunoblot assays. (+info)
Prevalence of hepatitis B, D and C virus infections among children and pregnant women in Moldova: additional evidence supporting the need for routine hepatitis B vaccination of infants.
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Rates of acute hepatitis B are high in Moldova, but the prevalence of chronic infection is unknown. In 1994, we surveyed children and pregnant women, collected demographic information, and drew blood for laboratory testing. Among the 439 children (mean age, 5 years), the prevalence of antibody to hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were 17.1 and 6.8%, respectively. Among the 1098 pregnant women (mean age, 26 years), 52.4% were anti-HBc-positive and 9.7% were HBsAg-positive. Of the HBsAg-positive pregnant women, 35.6% were hepatitis B e antigen (HBeAg) positive and 18.3% had antibodies to hepatitis D virus. The prevalence of antibody to hepatitis C virus was 1.4% in children and 2.3% in pregnant women. The high HBeAg prevalence among HBsAg-positive pregnant women and the high anti-HBc prevalence among children indicate that both perinatal and early childhood transmission contribute to the high hepatitis B virus endemicity in Moldova. (+info)