Vaccine- and hepatitis b immune
globulin-induced escape mutations of
hepatitis b virus surface antigen.
Date: Mon, 4 Jun 2001 08:32:46 -0400
From: hbv_research-list-owners@mail-list.com
Subject: Vaccine- and hepatitis b immune globulin-induced escape
mutations of
hepatitis b virus surface antigen.
1: J Biomed Sci 2001 May-Jun;8(3):237-47Vaccine- and hepatitis b immune
globulin-induced escape mutations ofhepatitis b virus surface
antigen.Cooreman MP, Leroux-Roels G, Paulij 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 inspite
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 acid145 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 his mutation on anti-HBs antibody recognition, compared with other
poin mutations in this antigenic domain. The clinical and
epidemiologica lsignificance 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 post transplantation 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