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减毒鼠伤寒沙门氏菌肠炎亚种载体递送病毒样颗粒诱导小鼠对猪圆环病毒 2 的保护性免疫应答。

Live attenuated Salmonella enterica serovar Choleraesuis vector delivering a virus-like particles induces a protective immune response against porcine circovirus type 2 in mice.

机构信息

College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.

Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611-0880, USA.

出版信息

Vaccine. 2022 Aug 5;40(33):4732-4741. doi: 10.1016/j.vaccine.2022.06.046. Epub 2022 Jun 27.

Abstract

The virus-like particles (VLPs) of porcine circovirus type 2 (PCV2) is an attractive vaccine candidate that retains the natural conformation of the virion but lacks the viral genome to replicate, thus balancing safety and immunogenicity. However, the assembly of VLPs requires cumbersome subsequent processes, hindering the development of related vaccines. In addition, as a subunit antigen, VLPs are defective in inducing cellular and mucosal immune responses. In this study, the capsid (Cap) protein of PCV2 was synthesized and self-assembled into VLPs in the recombinant attenuated S. Choleraesuis vector, rSC0016(pS-Cap). Furthermore, rSC0016(pS-Cap) induced a Cap-specific Th1-dominant immune response, mucosal immune responses, and neutralizing antibodies against PCV2. Finally, the virus genome copies in mice immunized with the rSC0016(pS-Cap) were significantly lower than those of the empty vector control group after challenge with PCV2. In conclusion, our study demonstrates the potential of using S. Choleraesuis vectors to delivery VLPs, providing new ideas for the development of PCV2 vaccines.

摘要

猪圆环病毒 2 型(PCV2)的病毒样颗粒(VLPs)是一种有吸引力的疫苗候选物,它保留了病毒粒子的天然构象,但缺乏复制的病毒基因组,从而平衡了安全性和免疫原性。然而,VLPs 的组装需要繁琐的后续过程,阻碍了相关疫苗的开发。此外,作为亚单位抗原,VLPs 在诱导细胞和黏膜免疫应答方面存在缺陷。在本研究中,PCV2 的衣壳(Cap)蛋白在重组减毒 S. Choleraesuis 载体 rSC0016(pS-Cap)中被合成并自我组装成 VLPs。此外,rSC0016(pS-Cap)诱导了 Cap 特异性 Th1 优势免疫应答、黏膜免疫应答和针对 PCV2 的中和抗体。最后,用 rSC0016(pS-Cap)免疫的小鼠在受到 PCV2 攻击后,其病毒基因组拷贝数明显低于空载体对照组。总之,本研究表明,使用 S. Choleraesuis 载体传递 VLPs 具有潜力,为 PCV2 疫苗的开发提供了新的思路。

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