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Updated: Sep 12, 2025
A "Plug-And-Display" Nanoparticle Vaccine Platform Based on Outer Membrane Vesicles Displaying SARS-CoV-2 Receptor-Binding Domain
Published on: July 25, 2022
Single self-cleaving mRNA vaccine expressing multiple viral structural proteins elicits robust immune responses and
Ruiming Yu1,2,3, Yingjie Bai1,2, Liping Zhang1,2
1State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou University, Lanzhou, China.
Abstract:
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∶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.
