A novel rabies vaccine based on infectious propagating particles derived from hybrid VEEV-Rabies replicon

EBioMedicine

Cheng-guang Zhang¹  Ling Zhao¹  Chen Chen²  Bo Zhang³  Ya-Nan Zhang³  Na Li³  Zhen Wang⁴  Cheng-Lin Deng⁴ 

[1] College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China;University of Chinese Academy of Sciences, Beijing 100049, China;Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China;State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, China;

关键词: Rabies;    VEEV;    Live attenuated vaccine;    Glycoprotein;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: Live attenuated vaccines (LAVs) can mimic natural infection and have advantages to stimulate a robust and sustained immune response as well as to confer long-term protection. However, safety concerns is one of the major obstacles for LAVs development. In an effort to achieve the optimal balance between immunogenicity and safety, researchers currently have taken different strategies for the development of LAVs. Methods: We constructed a novel infectious self-propagating hybrid replicon particle (PRP), VEEV-RABV-G, through replacing the entire structural proteins of the Venezuelan equine encephalitis virus (VEEV) with the glycoprotein of rabies virus (RABV-G) as the single structural protein. We evaluated the potential of VEEV-RABV-G as a safe live attenuated vaccine in mice model. Findings: We found that VEEV-RABV-G could self-propagate efficiently in cell culture and induce a robust humoral immunity and provide protection against virulent RABV challenge in immunized mice. Remarkably, VEEV-RABV-G is highly attenuated in both adult and sucking mice, causing much weaker inflammatory and apoptotic effects in the brains of infected adult mice and significantly lower weight loss and morbidity compared with the commonly used RABV-derived LAVs. Interpretation: This study reveals the feasibility of developing novel rabies vaccines based on the self-replicating PRPs. Funding: This work was supported by the National Key Research and Development Program of China (2016YFD0500400).

【 授权许可】

Unknown