- 作者: Michael P, Cooreman Geert Leroux-Roels Wilma P. Paulij
- 作者服務機構: Deparment of Gastroenterology and Hepatology, Academic Medical Cener, University of Amsterdam, AMsterdam, Department of Bioscience and Chemistry, Organon Teknika, Boxtel, The Netherlands; Center for Vaccinology, Ghent University, Ghent, Belgium
- 中文摘要: --
- 英文摘要: Hepatitis B virus surface antigen (H BsAg) vaccinationhas been shown to be effective in preventing hepatitis Bvirus (HBV) infection. The protection is based on theinduction of anti-HBs antibodies against a major clusterof antigenic epitopes of HBsAg, defined as the 'a' deter-minant region of small HBsAg. Prophylaxis of recurrentHBV infection in patients who have undergone livertransplantation for hepatitis B-related end-stage liver dis-ease is achieved by the administration of hepatitis Bimmune globulins (HBIg) derived from HBsAg-vacci-nated subjects. The anti-HBs-mediated immune pressureon HBV, however, seems to go along with the emer-gence and/or selection of immune escape HBV mutantsthat enable viral persistence in spite of adequate anti-body titers. These HBsAg escape mutants harbor singleor double point mutations that may significantly alter theimmunological characteristics of HBsAg. Most escapemutations that influence HBsAg recognition by anti-HBsantibodies are∣ocated in the second 'a' determinantloop. Notably, HBsAg with an arginine replacement forglycine at amino acid 145 is considered the quintessen-tial immune escape mutant because it has been isolatedconsistently in clinical samples of HBIg-treated individu-als and vaccinated infants of chronically infected moth-ers. Direct binding studies with monoclonal antibodiesdemonstrated a more dramatic impact of this mutationon anti-HBs antibody recognition, compared with otherpoint mutations in this antigenic domain. The clinicaland epidemiological significance of these emergingHBsAg mutants will be a matter of research for years tocome, especially as data available so far document thatthese mutants are viable and infectious strains. Strate-gies for vaccination programs and posttransplantationprophylaxis of recurrent hepatitis need to be developedthat may prevent immune escape mutant HBV fromspreading and to prevent these strains from becomingdominant during the next decennia.
- 中文關鍵字: --
- 英文關鍵字: Hepatitis B virus. HBsAg. Mutations. Vaccination. Hepatitis B immune globulin