An engineered VSV-vectored rabies vaccine with an RABV-G-L71S mutation

A replicating recombinant rabies vaccine, rVSV-RABV, was constructed using vesicular stomatitis virus (VSV) expressing the rabies virus glycoprotein (RABV-G, SAD-B19 strain). A leucine-to-serine mutation at position 71 (L71S) in the RABV-G extracellular domain significantly enhanced the viral titer and G protein expression. The derived strain, rVSV-RABV-L71S, demonstrated production and immunogenic advantages. As an inactivated vaccine formulated with GEL-02 adjuvant, it induced stronger neutralizing antibody responses, along with innate and Th1-biased T cell immunity in mice, compared to commercially inactivated vaccines. As a live vaccine, it conferred robust protection against the CVS-24 challenge in mice (NIH titer ∼4.8-fold higher than reference) and elicited superior neutralizing antibodies in dogs. Both inactivated and live rVSV-RABV-L71S formulations exhibited favorable safety profiles. rVSV-RABV-L71S represents a promising, low-cost, high-efficacy rabies vaccine candidate suitable for widespread use in developing countries.

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Publication Details

Journal
iScience
Published
2025-10-25
DOI
https://doi.org/10.1016/j.isci.2025.113714
Primary Topic
Rabies epidemiology and control
Type
article
Field-Weighted Citation Impact
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article

An engineered VSV-vectored rabies vaccine with an RABV-G-L71S mutation

Tianying Zhang, Ying-Bin Wang, Liqin Liu, Hangtian Ding et al.
iScience
Rabies epidemiology and control
article

An engineered VSV-vectored rabies vaccine with an RABV-G-L71S mutation

Tianying Zhang, Ying-Bin Wang, Liqin Liu, Hangtian Ding, Hualong Xiong, Ruitong Chen, Kegong Tian, Qingbing Zheng, M.-C. Chang, Yanan Zhu, Shuyu Wu, Shengyu Yan, Mingxi Yue, Hongchao Wu, Hui Huang, Yujuan Gao, Ningshao Xia, Wen-Rong Wu, Quan Yuan, Jie Lü, Jinlei Zhang, Yuan Cao
article en

Abstract

A replicating recombinant rabies vaccine, rVSV-RABV, was constructed using vesicular stomatitis virus (VSV) expressing the rabies virus glycoprotein (RABV-G, SAD-B19 strain). A leucine-to-serine mutation at position 71 (L71S) in the RABV-G extracellular domain significantly enhanced the viral titer and G protein expression. The derived strain, rVSV-RABV-L71S, demonstrated production and immunogenic advantages. As an inactivated vaccine formulated with GEL-02 adjuvant, it induced stronger neutralizing antibody responses, along with innate and Th1-biased T cell immunity in mice, compared to commercially inactivated vaccines. As a live vaccine, it conferred robust protection against the CVS-24 challenge in mice (NIH titer ∼4.8-fold higher than reference) and elicited superior neutralizing antibodies in dogs. Both inactivated and live rVSV-RABV-L71S formulations exhibited favorable safety profiles. rVSV-RABV-L71S represents a promising, low-cost, high-efficacy rabies vaccine candidate suitable for widespread use in developing countries.

iScienceVol. 28(11)
Xiamen University (CN), Henan Agricultural University (CN), Luoyang Institute of Science and Technology (CN)
Openalex Percentile: Top 67%
Rabies epidemiology and control
DOIOpen Access PDFOpenAlex
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