Hepatitis A virus (HAV) was the first of the hepatitis viruses to be successfully cultivated in vitro.This opened up the possibility that a vaccine could be developed to prevent disease.As HAV is a picornavirus, the model for a vaccine was established by polio for which both killed and live attenuated vaccines had been successfully developed.As the virus grew very poorly in early cell culture passages, it was reasoned that adaptation to cell culture might also attenuate the virus.In fact, cell culture adapted strains of HAV did exhibit attenuated phenotype in both tamarin monkeys and chimpanzees.However, strains that were selected appeared over-attenuated in clinical trials.