文献类型： 外文期刊

作者： Yu, Ruiming ¹ ; Bai, Yingjie ¹ ; Zhang, Liping ¹ ; Zhou, Peng ¹ ; Zhang, Zhongwang ¹ ; Yang, Jun ⁴ ; Lu, Yanzhen ¹ ; Wang, Dongsheng ¹ ; Peng, Yousheng ¹ ; Li, Dan ¹ ; He, Jian ¹ ; Wang, Yonglu ¹ ; Zhang, Quanwei ⁵ ; Yuan, Ligang ³ ; Guo, Huichen ¹ ; Pan, Li ¹ ; Liu, Xinsheng ¹ ;

作者机构： 1.Lanzhou Univ, Chinese Acad Agr Sci, State Key Lab Anim Dis Control & Prevent, Coll Vet Med,Lanzhou Vet Res Inst, Lanzhou, Peoples R China

2.Gansu Prov Res Ctr Basic Disciplines Pathogen Biol, Lanzhou, Peoples R China

3.Gansu Agr Univ, Coll Vet Med, Lanzhou, Peoples R China

4.Hunan Inst Anim & Vet Sci, Changsha, Peoples R China

5.Gansu Agr Univ, Coll Life Sci & Biotechnol, Lanzhou, Peoples R China

关键词： porcine deltacoronavirus (PDCoV); spike protein; membrane protein; nucleoprotein; mRNA vaccine; immunoprotection

期刊名称：JOURNAL OF VIROLOGY （ 影响因子：3.8； 五年影响因子：3.9 ）

ISSN： 0022-538X

年卷期： 2025 年

页码：

收录情况： SCI

摘要： As an emerging swine enteric coronavirus, porcine deltacoronavirus (PDCoV) poses a severe threat to the global swine industry and has demonstrated potential for cross-species transmission. Therefore, the development of safe and effective vaccines is a top priority for the future prevention and control of PDCoV. In this study, we first designed and prepared an mRNA vaccine, S2P-mRNA-LNP, that expresses the full-length S2P (E855P, V856P) protein of PDCoV. Animal experiments demonstrated that S2P-mRNA-LNP induced significantly stronger humoral and cellular immune responses in mice than did an inactivated vaccine. Then, we introduced the P2A self-cleaving peptide into the S2P-mRNA-LNP design, generating SMN-mRNA-LNP, an LNP-encapsulated mRNA vaccine that allows the simultaneous expression of three major structural proteins of PDCoV (S, M, and N) from a single mRNA. The immunization of piglets demonstrated that both S2P-mRNA-LNP and SMN-mRNA-LNP induced robust humoral immune responses. Notably, SMN-mRNA-LNP conferred significantly superior active immune protection in piglets (5/5) than did S2P-mRNA-LNP (4/5). Further immunization experiments in pregnant sows showed that piglets born to SMN-mRNA-LNP-vaccinated sows acquired high levels of IgG, IgA, and neutralizing antibodies through the ingestion of colostrum, conferring complete passive protection (5/5). The protective efficacy of SMN-mRNA-LNP was markedly superior to that of the inactivated vaccine. In conclusion, these findings demonstrate that SMN-mRNA-LNP is a novel and highly efficacious candidate vaccine against PDCoV. In addition, the design strategy of single mRNA-LNP simultaneously delivering multiple viral antigens in this study provides a new idea for the development of porcine intestinal coronavirus mRNA vaccine in the future.IMPORTANCEIn this study, we designed and developed a novel mRNA vaccine, SMN-mRNA-LNP, capable of expressing the three major structural proteins (S, M, and N) of PDCoV from a single mRNA. This vaccine conferred superior active immune protection on piglets to that conferred by S2P-mRNA-LNP expressing only the S protein. Furthermore, following the immunization of pregnant sows with SMN-mRNA-LNP, their colostrum showed remarkably high IgA antibody titers reaching 1 & ratio;105.4, representing a 25-fold increase over that in the inactivated vaccine group. By suckling, newborn piglets acquired significantly greater passive immunity, which ultimately conferred complete protection against PDCoV challenge.