Association of normal serum protein antigens with chimpanzee hepatitis B surface antigen particles

Vnek, J; Prince, Alfred M.; Hashimoto, Nobuo; Ikram, H.

doi:10.1002/jmv.1890020405

Cited by 8 publications

(2 citation statements)

References 17 publications

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“…Following challenge with live HBV, anti-HBe responses occurred only in animals in which HBsAg replication was detectable (Figs. [10][11][12][13][14]. Anti-HBe responses tended to accompany or follow the appearance of anti-HBc.…”

Section: Anti-hbe Responsesmentioning

confidence: 94%

A final report on safety and immunogenicity of a bivalent aqueous subunit HBV vaccine

Prince

Brotman

Purcell

et al. 1985

Journal of Medical Virology

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The bivalent form of an aqueous formalin-inactivated hepatitis B vaccine was evaluated for safety and immunogenicity in chimpanzees. To evaluate safety five animals were inoculated intravenously with vaccine containing 500 micrograms HBsAg and two animals with 50 micrograms. None of these animals developed hepatitis or any serologic marker indicative of the presence of residual live virus in the vaccine. Twenty-four animals were used to evaluate immunogenicity and protective efficacy. Seven of these immunized animals produced weak or no anti-HBs responses. Two doses of 50 micrograms HBsAg given subcutaneously 1 month apart protected each of four animals that were challenged with 10(3.5) CID50 HBV at 6 and 12 months after immunization and protected three of four animals challenged at 24 months against development of hepatitis or HBsAg. Three of 4 animals in each group immunized with two doses of 20, 10, or 5 micrograms HBsAg were similarly protected when challenged 6 months after immunization. Thirteen of 20 immunized animals that did not develop HBsAg after challenge with HBV developed anamnestic anti-HBs or anti-HBc responses between 2 and 18 months after challenge, indicating minimal replication of challenge virus. The time of onset and frequency of occurrence of these delayed responses was related to the titer of anti-HBs at the time of challenge. False positive Ausab test results were observed in quarantined chimpanzees. These were neither preceded by appearance of HBsAg nor accompanied by development of anti-HBc. In most cases these reactions were due to a reactant having a sedimentation coefficient and an electrophoretic mobility resembling that of IgM. This reactant generally did not appear to confer resistance to challenge with HBV. The humoral immune response was characterized as being entirely of the IgM class 2 weeks after immunization and switched entirely into the IgG class by 10-12 weeks after vaccine administration. At the time of challenge all animals with antibody had anti-HBs of subtype a.

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Section: Anti-hbe Responsesmentioning

confidence: 94%

A final report on safety and immunogenicity of a bivalent aqueous subunit HBV vaccine

Prince

Brotman

Purcell

et al. 1985

Journal of Medical Virology

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“…Such vaccines could contain unwanted antigenic components, derived from elsewhere in the virion or its associated particles, or from the host cells in which these were synthesized. It is difficult, ifnot impossible, to remove all detectable host components-e.g., human serum albumin, IgG, and some other serum proteins-from even the most highly purified HBsAg particles (45)(46)(47)(48). Indeed, when such particles derive from HBV e antigen-positive donors, they adsorb efficiently to aggregated human serum albumin (48).…”

Section: Munizationmentioning

confidence: 99%

Hepatitis B virus vaccine: identification of HBsAg/a and HBsAg/d but not HBsAg/y subtype antigenic determinants on a synthetic immunogenic peptide.

Prince¹,

Ikram²,

Hopp³

1982

Proc. Natl. Acad. Sci. U.S.A.

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On the basis of theoretical considerations, a peptide (H Discovery of hepatitis virus-specific antigens (1-3) and their association with the outer membrane ofhepatitis B virus (HBV) (4, 5) has led to rapid advances in the prevention of HBV infection. This has been achieved through detection of HBV carrier blood donors by testing for the HBV surface antigen (HBsAg) (6, 7), and by passive (8-12) and active (13-18) immunization.The protective effect of hepatitis B immune globulin, prepared from plasma selected for high anti-HBsAg content, as well as the demonstration that protective immunity can be induced, albeit at high cost, by the purified 23,000-dalton HBsAg polypeptide isolated from HBV-associated subviral particles (19), has suggested that anti-HBsAg is a protective antibody. Other surface specificities on the HBV virion could also play a similar role (18,20).HBsAg also exhibits generally mutually exclusive strain-specific subtype antigenic determinants-e.g., d/y (21) and w/r (22)-in addition to the determinant a common to all strains. Available evidence suggests that the subtype specificities play no role in providing protective immunity (23,24), and thus that HBsAg/a may be the critical determinant.It is thus ofobvious interest to learn the amino acid sequence of the antibody-combining site, or epitope, of HBsAg/a. Progress towards this goal has depended on two key advances: isolation and characterization of HBV DNA (25) and determination of its sequence through recombinant DNA methods (26)(27)(28)(29). This permitted prediction of the amino acid sequence of the product of the HBsAg gene (the s gene) (30,31). Using a theoretical model, Hopp and Woods (32) were then able to predict a putative dominant HBsAg epitope (termed H epitope): the sequence Lys-Pro-Thr-Asp-Gly-Asn corresponding to positions 141-146 on the HBsAg protein. They then synthesized a tetradecapeptide (H peptide) containing residues 138-149 of HBsAg plus two glycine residues at its COOH terminus, using classical solid-phase peptide synthetic methodology. The four cysteinyl residues were replaced by a-aminobutyric acid in order to prevent polymerization and other side reactions common to sulfhydryl-containing peptides. Polystyrene beads covalently coated with H peptide bound more "2I-labeled anti-HBsAg than did uncoated beads (33).We report herein confirmation of the prediction that the H peptide contains a major epitope for HBsAg, and we further demonstrate that this sequence of amino acids contains the HBsAg/a and HBsAg/d epitopes, but not the epitope ofHBsAg/ y or human serum albumin. Furthermore, we demonstrate that when bound to a carrier the peptide induces the synthesis of anti-HBsAg in vivo.MATERIALS AND METHODS H Epitope Polypeptide Preparations. Initial experiments were done with intact polystyrene beads (XE305A resin beads, Rohm and Hass, Philadelphia) on which the H peptide had been synthesized. These beads contained 10 mg of peptide per 25 mg.For immunization it was necessary to remove the peptide from the polystyrene ...

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Interaction Between Hepatitis B Surface Proteins and Monomeric Human Serum Albumin

et al. 1990

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HBsAg is known to bind to human serum albumin polymerized by glutaraldehyde, human serum albumin has been found in preparations of HBsAg by several investigators. However, it is not yet known whether natural human serum albumin binds to hepatitis B virus under physiological conditions. We studied the binding between natural or recombinant HBsAg and monomeric human serum albumin by immunological, biochemical and biophysical methods. The binding capacity of 20-nm HBs spheres was variable but ranged up to six molecules HSA/sphere. A reversible binding site for human serum albumin was exclusively localized in the preS2 domain, whereas the S domain was inactive in vitro. Human serum albumin copurified with HBsAg of human origin during gel chromatography or sucrose-gradient centrifugation. This human serum albumin was monomeric in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The preS2-bound part of the human serum albumin could be removed from HBsAg by high-salt, such as CsCl centrifugation, but another part could only be removed by treatment with a disulfide cleaving reagent. Most of this covalently bound human serum albumin was retained at the HBsAg particle after complete cleavage of medium-sized HBs protein with trypsin. This indicates a second way in which albumin binds irreversible to cysteine(s) of the small HBs protein (SHBs, P24 and GP27).

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Association of normal serum protein antigens with chimpanzee hepatitis B surface antigen particles

Cited by 8 publications

References 17 publications

A final report on safety and immunogenicity of a bivalent aqueous subunit HBV vaccine

A final report on safety and immunogenicity of a bivalent aqueous subunit HBV vaccine

Hepatitis B virus vaccine: identification of HBsAg/a and HBsAg/d but not HBsAg/y subtype antigenic determinants on a synthetic immunogenic peptide.

Interaction Between Hepatitis B Surface Proteins and Monomeric Human Serum Albumin

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