The mRNA vaccine expressing fused structural protein of PRRSV protects piglets against PRRSV challenge

The swine industry experiences substantial economic losses annually due to the porcine reproductive and respiratory syndrome virus (PRRSV). The limited protective efficacy of existing commercial vaccines against epidemic PRRSV underscores the urgent need for innovative solutions. The mRNA vaccines , which elicit robust immune responses, have emerged as a promising avenue in vaccine development. In this study, two distinct mRNA vaccines were engineered: one encoding the full-length GP5 and M proteins (GP5-M), and the other encoding the full-length N protein along with epitope peptide segments of the M and E proteins (NMEpep). Our findings indicate that, compared with NMEpep, piglets immunized with the GP5-M mRNA vaccine produced specific antibodies, exhibited elevated levels of PRRSV-specific IFN-γ, and demonstrated effective activation of CD4 + and CD8 + T cells as well as CD21 + B cells. Furthermore, the GP5-M vaccine conferred protective efficacy against HP-PRRSV challenge, evidenced by the mitigation of clinical symptoms, reduction in viral loads , and alleviation of tissue damage . In conclusion, this study presents a promising candidate vaccine for addressing epidemic PRRSV and establishes the GP5-M mRNA vaccine as a viable platform for the development of next-generation PRRSV vaccines . • The mRNA vaccines targeting the structural proteins of HP-PRRSV were engineered. • The GP5-M mRNA vaccine induced PRRSV-specific humoral and cellular immune responses. • The GP5-M mRNA vaccine protected piglets from HP-PRRSV challenge.