PRRSV vector vaccine based on VEEV-VSVG recombinant replicon elicits efficient immune responses in piglets

Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the most significant viral infectious diseases affecting the global swine industry. Eradicating PRRS remains a formidable challenge due to the high genetic diversity and the complexity of the host immune response. Currently, no commercial vaccine provides complete protection against Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection. This study aimed to construct a vector vaccine expressing PRRSV GP3, GP4, GP5, and M protein based on the Venezuelan equine encephalitis virus (VEEV) replicon system and to evaluate the immunogenicity in piglets. Here, we demonstrated that PRRSV GP3, GP4, GP5, and M protein could be successfully expressed in BHK-21 cells infected with recombinant replicons. Notably, the expression exhibiting both time-dependence and passage stability. Recombinant replicons produced infectious virus-like vesicles (VLVs), displayed consistent biological traits, forming plaques of uniform size and morphology post-infection. Building upon these characteristics, we developed a PRRSV vector vaccine incorporating these four recombinant replicons and systematically evaluated immunogenicity and protective efficacy. The analysis revealed that the vector vaccine elicited robust humoral and cellular immune responses, in contrast to the negative control group. In challenge experiments, immunization with vector vaccine demonstrated significant protective effects, including a substantial reduction in serum viral loads, accelerated clearance of viremia and decreased viral loads in target tissues.