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A Genetically Engineered Bivalent Vaccine Coexpressing a Molecular Adjuvant against Classical Swine Fever and Porcine Epidemic Diarrhea

文献类型： 外文期刊

作者： Wang, Hao 1 ; Yi, Weicheng 1 ; Qin, Huan 1 ; Wang, Qin 2 ; Guo, Rui 3 ; Pan, Zishu 1 ;

作者机构： 1.Wuhan Univ, Coll Life Sci, State Key Lab Virol, Wuhan 430072, Peoples R China

2.China Inst Vet Drug Control, World Org Anim Hlth Reference Lab Class Swine Feve, Beijing 100081, Peoples R China

3.Hubei Acad Agr Sci, Inst Anim Husb & Vet, Key Lab Prevent & Control Agents Anim Bacteriosis, Minist Agr & Rural Affairs,Hubei Prov Key Lab Anim, Wuhan 430064, Peoples R China

关键词： classical swine fever virus; porcine epidemic diarrhea virus; bivalent vaccine; VISA; molecular adjuvant

期刊名称：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES （ 影响因子：5.6； 五年影响因子：6.2 ）

ISSN： 1661-6596

年卷期： 2023 年 24 卷 15 期

页码：

收录情况： SCI

摘要： Classical swine fever (CSF) and porcine epidemic diarrhea (PED) are highly contagious viral diseases that pose a significant threat to piglets and cause substantial economic losses in the global swine industry. Therefore, the development of a bivalent vaccine capable of targeting both CSF and PED simultaneously is crucial. In this study, we genetically engineered a recombinant classical swine fever virus (rCSFV) expressing the antigenic domains of the porcine epidemic diarrhea virus (PEDV) based on the modified infectious cDNA clone of the vaccine strain C-strain. The S1N and COE domains of PEDV were inserted into C-strain cDNA clone harboring the mutated 136th residue of N-pro and substituted 3 & PRIME;UTR to generate the recombinant chimeric virus vC/SM3 & PRIME;UTRN-S1NCOE. To improve the efficacy of the vaccine, we introduced the tissue plasminogen activator signal (tPAs) and CARD domain of the signaling molecule VISA into vC/SM3 & PRIME;UTRN-S1NCOE to obtain vC/SM3 & PRIME;UTRN-tPAsS1NCOE and vC/SM3 & PRIME;UTRN-CARD/tPAsS1NCOE, respectively. We characterized three vaccine candidates in vitro and investigated their immune responses in rabbits and pigs. The N-D136N(pro) mutant exhibited normal autoprotease activity and mitigated the inhibition of IFN-& beta; induction. The introduction of tPAs and the CARD domain led to the secretory expression of the S1NCOE protein and upregulated IFN-& beta; induction in infected cells. Immunization with recombinant CSFVs expressing secretory S1NCOE resulted in a significantly increased in PEDV-specific antibody production, and coexpression of the CARD domain of VISA upregulated the PEDV-specific IFN-& gamma; level in the serum of vaccinated animals. Notably, vaccination with vC/SM3 & PRIME;UTRN-CARD/tPAsS1NCOE conferred protection against virulent CSFV and PEDV challenge in pigs. Collectively, these findings demonstrate that the engineered vC/SM3 & PRIME;UTRN-CARD/tPAsS1NCOE is a promising bivalent vaccine candidate against both CSFV and PEDV infections.

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