Immunogenicity of experimentally combined hepatitis A and hepatitis E vaccine at different dosage ratio

    DONG Chen, DAI Xing, MENG Jiª²hong*

    Department of Microbiology and Immunology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China

    [Abstract] AIM: To evaluate the immunogenicity of experimentally combined hepatitis A and hepatitis E (cHA+E) vaccine and analyze the interactions between the two antigenic components in vaccine. METHODS: Nine different dosage ratio of the cHA+E vaccine, A500+E200, A500+E100, A500+E50, A250+E200, A250+E100, A250+E50, A125+E200, A125+E100 and A125+E50 (U+mg)/L, was prepared from an inactivated hepatitis A (HA) vaccine and a hepatitis E (HE) vaccine. 120 mice were immunized with the cHA+E vaccine, HA vaccine and HE vaccine alone in different doses, respectively. Mice were bled before immunization and 2, 4, 6, 8, 10, 12 and 14 weeks post immunization. Specific antibodies against hepatitis A and E viruses were detected by ELISA and neutralization assay. RESULTS: After immunization with different dosages of cHA+E vaccine, all animals developed hepatitis A virus antibody (antiª²HAV) and hepatitis E virus antibody (antiª²HEV). Antiª²HAV responses increased with the concentration of the HA vaccine component in the cHA+E vaccine. Antiª²HAV neutralizing antibody titers reached 1¡Ã1 024 when mice were immunized with cHA+E vaccine prepared from higher dosage (500 U/mL) of the HA vaccine. The titers only reached 1¡Ã512 when lower dosages (250 and 125 U/mL) of HA vaccine were applied. However, different dosages (200, 100 and 50 mg/L) of the HE vaccine component in the cHA+E vaccine developed no effects on the production of antiª²HAV neutralizing antibody. In addition, comparing with the single HE vaccine, the cHA+E vaccine induced higher level of antiª²HEV response. The antiª²HEV level increased with the concentration of HA vaccine component in the cHA+E vaccine. However, there was no obvious relationship between the antiª²HEV levels and the different dosages (200, 100 and 50 mg/L)of the HE vaccine component in the cHA+E vaccine. Immune sera elicited by the cHA+E vaccine neutralized HEV infectivity when detected by an in vitro RTª²nPCRª²based HEV neutralization assay. CONCLUSION: In cHA+E vaccine, the HA vaccine component can increase the immunogenicity of the HE vaccine component, and the HE vaccine component plays no adverse effects on the immunogenicity of the HA vaccine component. ......