Enhanced immunogenicity induced by an alphavirus replicon-based pseudotyped baculovirus vaccine against porcine reproductive and respiratory syndrome virus.

摘要

Pseudotyped baculovirus has emerged as a promising vector for vaccine development and gene therapy. Alphaviruses, such as Semliki Forest virus (SFV), have also received considerable attention for use as expression vectors because of their self-replicating properties. In this study, pseudotyped baculovirus containing the hybrid cytomegalovirus (CMV) promoter/SFV replicon was used as a vector to co-express the GP5 and M proteins of porcine reproductive and respiratory syndrome virus (PRRSV). The immunogenicity of the resulting recombinant baculovirus (BV-SFV-5 m6) was compared with the pseudotyped baculovirus vaccine (BV-CMV-5 m6), in which the expression of GP5 and M were driven by the CMV promoter only. In vitro, BV-SFV-5 m6 exhibited enhanced expression of foreign proteins and also caused apoptosis in transduced cells. After immunization in BALB/c mice, BV-SFV-5 m6 induced strong GP5-specific ELISA antibodies and neutralizing antibodies against homologous and heterologous viruses, along with dose sparing. Further analysis of the cell-mediated immune response showed that BV-SFV-5 m6 elicited a Th1-dominant immune response that was greater than that elicited by BV-CMV-5 m6. Taken together, the results of this study indicate that a baculovirus containing the hybrid CMV promoter/alphavirus replicon can be utilized as an alternative strategy to develop an efficacious vaccine against PRRSV infection.