猪流行性腹泻mRNA疫苗的制备与免疫原性评价

Preparation and immunogenicity evaluation of mRNA vaccine against porcine epidemic diarrhea

摘要:

猪流行性腹泻（porcine epidemic diarrhea，PED）是一种可引起仔猪高致死率的传染性疾病，尽管已有灭活疫苗和减毒活疫苗上市，但由于病毒变异频繁导致保护效力欠佳，发病率依然居高不下。本研究首次制备了PED mRNA候选疫苗，并在小鼠和妊娠母猪上评价了其免疫原性，证明了基于病毒受体结合区异源二聚体的mRNA候选疫苗具有良好的免疫原性，可在小鼠上高效诱导体液和细胞免疫应答，单次免疫血清中和抗体滴度达到1：300以上，并在妊娠母猪上诱导了与灭活疫苗相近的中和抗体水平，实现了100%抗体转阳。本研究为PED mRNA疫苗的进一步产业化奠定了基础。

Abstract:

Porcine epidemic diarrhea (PED) is a highly contagious disease that causes high mortality in suckling piglets. Although several licensed inactivated and live attenuated vaccines were widely used, the infection rate remains high due to unsatisfactory protective efficacy. In this study, mRNA vaccine candidates against PED were prepared, and their immunogenicity was evaluated in mice and pregnant sows. The mRNA PED vaccine based on heterodimer of viral receptor binding region (RBD) showed good immunogenicity. It elicited robust humoral and cellular immune responses in mice, and the neutralizing antibody titer reached 1:300 after a single vaccination. Furthermore, it induced neutralizing antibody level similar to that of the inactivated vaccine in pregnant sows. This study developed a new design of PED vaccine based on the mRNA-RBD strategy and demonstrated the potential for clinical application.