Vaccine- and hepatitis b immune globulin-induced escape mutations of hepatitis b virus surface antigen.

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1: J Biomed Sci 2001 May-Jun;8(3):237-47

Vaccine- and hepatitis b immune globulin-induced escape mutations of

hepatitis b virus surface antigen.

Cooreman MP, Leroux-Roels G, ij WP.

Department of Gastroenterology and Hepatology, Academic Medical Center,

University of Amsterdam, Amsterdam, The Netherlands.

Hepatitis B virus surface antigen (HBsAg) vaccination has been shown to be

effective in preventing hepatitis B virus (HBV) infection. The protection is

based on the induction of anti-HBs antibodies against a major cluster of

antigenic epitopes of HBsAg, defined as the 'a' determinant region of small

HBsAg. Prophylaxis of recurrent HBV infection in patients who have undergone

liver transplantation for hepatitis B-related end-stage liver disease is

achieved by the administration of hepatitis B immune globulins (HBIg)

derived from HBsAg-vaccinated subjects. The anti-HBs-mediated immune

pressure on HBV, however, seems to go along with the emergence and/or

selection of immune escape HBV mutants that enable viral persistence in

spite of adequate antibody titers. These HBsAg escape mutants harbor single

or double point mutations that may significantly alter the immunological

characteristics of HBsAg. Most escape mutations that influence HBsAg

recognition by anti-HBs antibodies are located in the second 'a' determinant

loop. Notably, HBsAg with an arginine replacement for glycine at amino acid

145 is considered the quintessential immune escape mutant because it has

been isolated consistently in clinical samples of HBIg-treated individuals

and vaccinated infants of chronically infected mothers. Direct binding

studies with monoclonal antibodies demonstrated a more dramatic impact of

this mutation on anti-HBs antibody recognition, compared with other point

mutations in this antigenic domain. The clinical and epidemiological

significance of these emerging HBsAg mutants will be a matter of research

for years to come, especially as data available so far document that these

mutants are viable and infectious strains. Strategies for vaccination

programs and posttransplantation prophylaxis of recurrent hepatitis need to

be developed that may prevent immune escape mutant HBV from spreading and to

prevent these strains from becoming dominant during the next decennia.

Copyright 2001 National Science Council, ROC and S. Karger AG, Basel

PMID: 11385295 [PubMed - in process]