Infectivity and vaccination efficacy studies in animal models of HBV S and pol gene mutants.
Infectious HBV wild-type and mutant clones were produced in vitro with three mutations in pol (rtV173L plus rtL180M plus rtM204V) or with a single mutation in the S gene (sG145R) and inoculated in treatment-naive chimpanzees. Intravenous inoculation of these mutants in chimpanzees resulted in HBV infection; the pol mutations remained stable, whereas the sG145R mutation reverted to wild type during viraemia. Additional hepatitis B vaccine efficacy studies conducted in chimpanzees showed lack of sterilizing immunity against the pol mutant. Whether such mutants can transmit to and infect vaccinated humans requires further investigation.
Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA. skamili@cdc.gov
Saleem
S
Kamili
D000818:Animals; D004195:Disease Models, Animal; D015751:Genes, pol / Q000235:genetics* / Q000276:immunology; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000235:genetics* / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D009154:Mutation; D002679:Pan troglodytes; D016896:Treatment Outcome; D014611:Vaccination
D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines