Studies in Chimpanzees of Live, Attenuated Hepatitis A Vaccine Candidates

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Abstract
Human hepatitis A virus (HAV) was attenuated in virulence for chimpanzees by passage in FRhK6 [fetal rhesus monkey kidney] and human diploid lung fibroblast [WI-38, MRC5] cell cultures. Several variants were developed by passage in cell cultures which showed different levels of virulence/attenuation for chimpanzees. These results were compared to those previously obtained with marmosets. Generally, most variants behaved similarly in the 2 animals. Two chimpanzees which gave vaccine-like responses following inoculation with HAV cell culture variants were challenged with virulent HAV. Both animals were immune to HAV infection. These findings provide further evidence for the feasibility of developing live, attenuated human HAV vaccines.