Immunogenicity of wild-type and vaccine strains of Japanese encephalitis virus and the effect of haplotype restriction on murine immune responses

Abstract

The Chinese live attenuated Japanese encephalitis (JE) virus vaccine clone SA14-14-2 produced in primary hamster kidney (PHK) cells has been adapted to primary dog kidney cells (PDK) for use as a live attenuated human vaccine. In this study we have compared the immunogenicity in mice of SA14-14-2 (PDK) and SA14-14-2 (PHK); also included was the wild-type parent to the vaccine clones, SA14, and another wild-type JE virus strain Nakayama (original). It was found that Balb/c (H-2 d) mice given a single dose of 10 3 or 10 6 p.f.u. of live SA14-14-2 (PHK) virus elicited a superior neutralizing (N) antibody response as compared to the same dosages of live SA14-14-2 (PDK) virus. However, if the vaccine clones were inactivated and administered in a two-dose regime the N antibody response elicited was similar for the two viruses. This observation may be explained by differences in the replication efficiency in vivo of the respective vaccine clones. The humoral immune response to all the virus strains in this study elicited by different inbred mouse strains each carrying a discrete haplotype (Balb/c (H-2 d), C3H (H-2 k), C57BL/6 (H-2 b)) were also assessed using haemagglutination inhibition (HAI) and N assays. Viruses were shown to elicit patterns of high and low N-antibody response depending on the major histocompatibility complex (MHC) make-up of the mouse strains. However, the patterns did not necessarily coincide when HAI and N titre reactivity patterns were compared for the same virus strain.