Human hepatitis A virus (HAV) was first grown in cell cultures four and one-half years ago, enabling significant progress toward the development of HAV
vaccines.
Vaccine development in a number of laboratories has proceeded on three fronts: 1) live,
attenuated vaccine of cell culture origin; 2)
inactivated vaccine of cell culture origin; and 3) genetic
recombinant vaccines. Our studies to date have focused most heavily on the development of a live, attenuated HAV
vaccine, although we have also made a prototype killed HAV
vaccine form infected marmoset liver which induced
anti-HAV and solid immunity to
infection in marmosets. HAV was attenuated in virulence for both marmosets and chimpanzees by serial passaging in fetal rhesus monkey kidney cells and human diploid embryonic lung fibroblasts. A number of variants were produced which showed different levels of virulence/attenuation in these animal models. Some variants showed desirable live
vaccine-like properties (little or no induction of
enzyme elevations; little or no liver histologic change; retention of
anti-HAV induction capacity). Vaccinated animals were solidly immune to challenge with virulent HAV. Experimental
vaccines have been prepared from several attenuated HAV variants and preliminary studies in humans are planned.