Safety and immunogenicity of lyophilized, live attenuated hepatitis A vaccine in non-human primate model

Objective To evaluate the safety and immunogenicity of lyophilized, live at tenuated hepatitis A vaccine (H2 strain) in rhesus monkeys. Methods Nine adult rhesus monkeys were used as experimental animals. The rh esus monkeys without anti-HAV were divided randomly into the aqueous vaccin ation group (4 rhesus monkeys), the lyophilized vaccination group (3 rhesus monkeys), and the control group (2 rhesus monkeys). Monkeys were inoculate d by intramuscular injection, with control monkeys being inoculated with Mi nimum Essential Medium Eagle (MEM). Following vaccination, the monkeys were observed for the development of diarrhoea and other adverse side-effects, such as changes in appetite, frequency of defaecation and stool consistency for seven days. At the weeks 2, 3, 4, 6, 8, 10 and 12 positnoculation, the peripheral blood was collected from all animals and assayed for anti-HAV a nd alanine aminotransferase ( ALT) and aspartate aminotransferase (AST), at weeks 0, 4 and 8 postinocuation, needle-biopsy specimens were taken at wee ks 0, 4, 8 and 12, all monkeys were sacrificed and tissue samples were take n from liver, lung, heart, kidney and brain for pathological examination at week 12. Results Animals were immunized with a dose of 7.0 logTCID(50)/ml which is s table after freeze-drying. During the 12-week observation, no animals showe d abnormal elevations of liver enzymes (ALT and AST) and no change in appet ite or activity. Two monkeys (one in the aqueous group and the other in lyo philized group) showed possible lesions at week 8. The lyophilized vaccine, in addition to eliciting an anti-HAV IgG response similar to aqueous vacci ne (P > 0.05), also showed IgM anti-HAV response at week 2 which was not ob served with aqueous vaccine. Conclusions These results demonstrate that lyophilized, live hepatitis A va ccine is safe and highly immunogenic in primates, supporting its further ev aluation in human clinical studies.