Merck + Co., Inc.

Paula A Giesa

Philip J Provost

Maurice R Hilleman

William J McAleer

Hepatitis A virus is attenuated in virulence by in vitro passage in susceptible cell cultures, without prior passage in a subhuman primate. This process results in a live, attenuated hepatitis A virus vaccine suitable for human disease prevention.

Cell culture of hepatitis A virus

Hepatitis A virus is attenuated by propagation in cell culture in vitro by direct inoculation of the cell cultures with a human clinical specimen containing the virus.

Attenuated hepatitis A virus

Hepatitus A virus is grown in Vero cells after passage in in vitro cell culture. Virus replication and continued passage in Vero cells requires extended incubation times, up to about four weeks, for early passages and incubation temperatures no higher than about 32.degree. C. Continued passage results in a significant decrease in incubation time and an increase in virus yield. Cultivation of hepatitus A virus in Vero cells meets the development requirements for an inactivated human vaccine.

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Lansdale, PA, United States of America

Paula A Giesa