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.