Hepatitis A virus has been successfully adapted to growth in African green monkey kidney tissue culture. Over 28 serial passages have been achieved, with infectivity titers as high as 1 hundred million infectious units per ml of cell concentrate. The virus is predominantly cell-associated and does not produce cytopathic effects (CPE). It was attenuated for chimpanzees after 10 serial tissue culture passages; reevaluation of the virus in chimpanzees after 20 tissue culture passages indicates the virus infectivity and attenuation have remained the same as at passage level 10. The attenuated virus has been shown not to revert to virulence during serial passage through chimpanzees. Immunization of chimpanzees with the attenuated virus is protective. The tisse culture-adapted HAV has been 3X cloned. These clones have been characterized in chimpanzees and marmosets.
