Protection against hepatitis B virus infection by immunization with hepatitis B core antigen

Iwarson, Sten; Tabor, Edward; Thomas, Howard; Snoy, Philip; Gerety, Robert J.

doi:10.1016/0016-5085(85)90148-9

Cited by 106 publications

(42 citation statements)

References 13 publications

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“…The first is that HBcAg/HBeAg-specific T helper cells can elicit anti-envelope antibodies that neutralize viruses (Milich et al, 1987 b) and this phenomenon could explain the ability of HBc or WHc vaccination to protect against HBV/WHV infection or at least against liver disease. Although our animals did not appear to develop anti-WHs, it is possible that our assay system is not sensitive enough to detect low levels of anti-WHs; in the studies by Iwarson et al (1985) and Murray et al (1984Murray et al ( , 1987 only three of seven animals seroconverted to anti-WHs after challenge. Another explanation which would need to be proved experimentally is that after immunization with WHcAg, T helper cell activity for cytotoxic T cell precursors is induced.…”

Section: Discussionmentioning

confidence: 81%

“…Recombinant WHc protein also assembles to form core particles similar to native core particles, which can be easily purified in large amounts. HBcAg has been shown to be highly immunogenic even without adjuvant (Iwarson et al, 1985) and might be used as an alternative vaccine against HBV infection e.g. in non-responders or low responders to HBsAg.…”

confidence: 99%

“…Anti-HBc passively transmitted to newborns from mothers who are chronic carriers of HBV do not protect these babies from HBV infection (Beasley et al, 1977), indicating that these antibodies do not neutralize the virus. Murray et al (1984Murray et al ( , 1987 and Iwarson et al (1985) demonstrated that immunization of chimpanzees with the core protein of HBV provided complete or partial protection from HBV infection. In Iwarson's study, three chimpanzees were completely protected.…”

Section: Introductionmentioning

confidence: 99%

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Protection of Woodchucks from Infection with Woodchuck Hepatitis Virus by Immunization with Recombinant Core Protein

Roos

Fuchs²,

Roggendorf³

1989

Journal of General Virology

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SUMMARYWoodchucks were immunized with recombinant woodchuck hepatitis virus (WHV) core antigen (WHcAg) to investigate whether such immunization protects against WHV infection. The C gene was cloned into a pUC12 vector and expressed in Escherichia coll. Core particles purified by sucrose and CsC1 gradient centrifugation had a buoyant density of 1-37 g/ml which corresponded to the density of WHcAg particles present in chronically infected liver. Two animals immunized with the recombinant antigen developed high antibody titres and were protected against infection after challenge with WHV. The surface antigen (WHsAg) and WHV DNA were not detected in the sera of immunized animals after challenge and these animals did not develop anti-WHs. Three control animals developed a typical WHV infection. The protection from WHV infection may depend not on the presence of antibodies against the core protein but on a cellular immune response to WHcAg.

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Section: Discussionmentioning

confidence: 81%

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Protection of Woodchucks from Infection with Woodchuck Hepatitis Virus by Immunization with Recombinant Core Protein

Roos

Fuchs²,

Roggendorf³

1989

Journal of General Virology

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“…Anti-HBc antibodies have been associated with active virus replication. Recently, a possible role of immune responses to HBcAg in protection against hepatitis B has been suggested (Prince, 1984;Stephen, Prince & Brotman, 1984;Iwarson et al, 1985), and the modulatingeffeet of anti-HBc antibodies in virus persistence and maternal transmission has been postulated (Alexander & Eddleston, 1986). However, all studies were based on the measurement of titres and subclasses of anti-HBc antibodies or on T cell-mediated immune responses.…”

Section: Discussionmentioning

confidence: 99%

“…Paradoxically, immune responses to HBcAg may also be significant in immunity to HBV. Immunization of chimpanzees with either recombinant-derived or liver-derived HBcAg particles results in protection against HBV challenge (Murray et al, 1984;Iwarson et al, 1985). The basis of this protection is unknown, although prior sensitization of mice with HBcAg or synthetic peptide analogues can potentiate B cell responses to the outer surface coat (HBsAg) determinants on subsequent exposure to HBV (Milich e?…”

Section: Introductionmentioning

confidence: 99%

The affinity of anti-HBc antibodies in acute and chronichepatitis B infection

Wen

Duan

Howard

et al. 1990

Clinical and Experimental Immunology

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SUMMARYAntibodies to hepatitis B core antigen (anti-HBc) are found in the sera of all individuals infected with hepatitis B virus. A role for these antibodies has been suggested in determining the outcome of infection. In this study, the affinity of anti-HBc antibodies in asymptomatic virus carriers was compared with that of antibodies present in the sera of patients with chronic liver disease. Persistently infected individuals with no evidence of clinical disease were found to have anti-HBc antibodies of greater affinity, compared with the chronic liver disease group. Sera from patients with chronic hepatitis contained high levels of low-affinity antibody whereas antibody levels in asymptomatic carriers were significantly lower. These findings are discussed in relation to the predicted role of antiHBc antibodies in mediating hepatitis B virus-related hepatocellular injury.

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Mutated epitopes of hepatitis B surface antigen fused to the core antigen of the virus induce antibodies that react with the native surface antigen

Shiau

Murray

1997

J. Med. Virol.

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Fusion of peptide epitopes to the core antigen (HBcAg) of hepatitis B virus (HBV) enhances their immunogenicity, both quantitatively and qualitatively. In a number of vaccine-induced mutants of HBV, glycine145 of the surface antigen S polypeptide (HBsAg) has been replaced by arginine, resulting in loss of cross-reactivity with antibodies to normal (wild-type) HBsAg. HBcAg fusion proteins carrying the immunodominant epitope of HBsAg, in which glycine145 was replaced by arginine, glutamic acid, or lysine, were produced in Escherichia coli and formed particles that displayed HBc antigenicity and immunogenicity similar to that of HBcAg itself. The fusion proteins also elicited T-cell proliferative responsiveness to HBcAg and HBsAg. Fusions carrying either wild-type or mutated epitopes of HBsAG showed HBs antigenicity in immunoblot analysis and antigen-capture immunoradiometric assay, but both mutant and wild-type derivatives induced antibodies that cross-reacted with wild-type HBsAG. The results emphasise the potential for HBcAg fusion proteins in vaccines by broadening the antibody response in a way that could confer protection against both wild-type and variant form of HBV.

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Protection against hepatitis B virus infection by immunization with hepatitis B core antigen

Cited by 106 publications

References 13 publications

Protection of Woodchucks from Infection with Woodchuck Hepatitis Virus by Immunization with Recombinant Core Protein

Protection of Woodchucks from Infection with Woodchuck Hepatitis Virus by Immunization with Recombinant Core Protein

The affinity of anti-HBc antibodies in acute and chronichepatitis B infection

Mutated epitopes of hepatitis B surface antigen fused to the core antigen of the virus induce antibodies that react with the native surface antigen

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