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

To evaluate the safety and immunogenicity of lyophilized, live attenuated hepatitis A vaccine (H2 strain) in rhesus monkeys.

Nine adult rhesus monkeys were used as experimental animals. The rhesus monkeys without anti-HAV were divided randomly into the aqueous vaccination group (4 rhesus monkeys), the lyophilized vaccination group (3 rhesus monkeys), and the control group (2 rhesus monkeys). Monkeys were inoculated by intramuscular injection, with control monkeys being inoculated with Minimum 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 and alanine aminotransferase (ALT) and aspartate aminotransferase (AST), at weeks 0, 4 and 8 postinocuation, needle-biopsy specimens were taken at weeks 0, 4, 8 and 12, all monkeys were sacrificed and tissue samples were taken from liver, lung, heart, kidney and brain for pathological examination at week 12.

Animals were immunized with a dose of 7.0 logTCID50/ml which is stable after freeze-drying. During the 12-week observation, no animals showed abnormal elevations of liver enzymes (ALT and AST) and no change in appetite or activity. Two monkeys (one in the aqueous group and the other in lyophilized group) showed possible lesions at week 8. The lyophilized vaccine, in addition to eliciting an anti-HAV IgG response similar to aqueous vaccine (P > 0.05), also showed IgM anti-HAV response at week 2 which was not observed with aqueous vaccine.

These results demonstrate that lyophilized, live hepatitis A vaccine is safe and highly immunogenic in primates, supporting its further evaluation in human clinical studies.