Search tips
Search criteria 


Logo of jcinvestThe Journal of Clinical Investigation
J Clin Invest. 1992 December; 90(6): 2543–2547.
PMCID: PMC443413

Loss of the common "A" determinant of hepatitis B surface antigen by a vaccine-induced escape mutant.


A previous study (Carman, W. F., A. R. Zanetti, P. Karayiannis, J. A. Waters, G. Manzillo, E. Tanzi, A. J. Zuckerman, and H. C. Thomas. 1990. Lancet. 336:325-329) demonstrated a variant hepatitis B surface antigen (HBsAg) in a vaccinated child born to a hepatitis B virus-infected mother. A substitution of arginine for glycine at amino acid 145 in HBsAg was observed. In this study the effect of this substitution on the common "a" determinant of this protein, against which protective immunity is directed, is investigated. Using recombinant HBsAg with and without the amino acid substitution, the binding of monoclonal antibodies that recognize different epitopes of the "a" determinant, was shown to be destroyed by the presence of arginine at amino acid 145. In convalescent and vaccinee sera, antibody binding to HBsAg was not inhibited by the variant HBsAg. Immunization with the variant HBsAg, although eliciting a high titer antibody that recognized the variant, produced a low titer of antibody recognizing the native protein. Studies in mice demonstrate that the immunogenicity of the variant protein is also substantially altered. The data presented here demonstrate that this variant evades the known protective anti-HBs response and lends support to the suggestion that this mutation arose as the result of immune pressure.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (754K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Le Bouvier GL, Capper RA, Williams AE, Pelletier M, Katz AJ. Concurrently circulating hepatitis B surface antigen and heterotypic anti-HBs antibody. J Immunol. 1976 Dec;117(6):2262–2264. [PubMed]
  • Koziol DE, Alter HJ, Kirchner JP, Holland PV. The development of HBsAg-positive hepatitis despite the previous existence of antibody to HBsAg. J Immunol. 1976 Dec;117(6):2260–2262. [PubMed]
  • Szmuness W, Stevens CE, Harley EJ, Zang EA, Oleszko WR, William DC, Sadovsky R, Morrison JM, Kellner A. Hepatitis B vaccine: demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States. N Engl J Med. 1980 Oct 9;303(15):833–841. [PubMed]
  • Jilg W, Lorbeer B, Schmidt M, Wilske B, Zoulek G, Deinhardt F. Clinical evaluation of a recombinant hepatitis B vaccine. Lancet. 1984 Nov 24;2(8413):1174–1175. [PubMed]
  • Imai M, Goto A, Nishioka K, Kurashina S, Miyakawa Y. Antigenicity of reduced and alkylated Australia antigen. J Immunol. 1974 Jan;112(1):416–419. [PubMed]
  • Mishiro S, Imai M, Takahashi K, Machida A, Gotanda T, Miyakawa Y, Mayumi M. A 49,000-dalton polypeptide bearing all antigenic determinants and full immunogenicity of 22-nm hepatitis B surface antigen particles. J Immunol. 1980 Apr;124(4):1589–1593. [PubMed]
  • Ashton-Rickardt PG, Murray K. Mutants of the hepatitis B virus surface antigen that define some antigenically essential residues in the immunodominant a region. J Med Virol. 1989 Nov;29(3):196–203. [PubMed]
  • Zanetti AR, Tanzi E, Manzillo G, Maio G, Sbreglia C, Caporaso N, Thomas H, Zuckerman AJ. Hepatitis B variant in Europe. Lancet. 1988 Nov 12;2(8620):1132–1133. [PubMed]
  • Carman WF, Zanetti AR, Karayiannis P, Waters J, Manzillo G, Tanzi E, Zuckerman AJ, Thomas HC. Vaccine-induced escape mutant of hepatitis B virus. Lancet. 1990 Aug 11;336(8711):325–329. [PubMed]
  • Waters JA, Brown SE, Steward MW, Howard CR, Thomas HC. Analysis of the antigenic epitopes of hepatitis B surface antigen involved in the induction of a protective antibody response. Virus Res. 1992 Jan;22(1):1–12. [PubMed]
  • Harford N, Cabezon T, Crabeel M, Simoen E, Rutgers A, De Wilde M. Expression of hepatitis B surface antigen in yeast. Dev Biol Stand. 1983;54:125–130. [PubMed]
  • Harford N, Cabezon T, Colau B, Delisse AM, Rutgers T, De Wilde M. Construction and characterization of a Saccharomyces cerevisiae strain (RIT4376) expressing hepatitis B surface antigen. Postgrad Med J. 1987;63 (Suppl 2):65–70. [PubMed]
  • Wampler DE, Lehman ED, Boger J, McAleer WJ, Scolnick EM. Multiple chemical forms of hepatitis B surface antigen produced in yeast. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6830–6834. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation