Journal: iScience / Year: 2025 Title: An engineered VSV-vectored rabies vaccine with an RABV-G-L71S mutation. Authors: Mingxi Yue / Yuhe Zhu / Hongchao Wu / Siping Yan / Jinlei Zhang / Mengqi Chang / Liqin Liu / Hui Huang / Jie Lu / Wenrong Wu / Ruitong Chen / Shuyu Wu / Yibing Gao / Yujiao Cao / Hangtian ...Authors: Mingxi Yue / Yuhe Zhu / Hongchao Wu / Siping Yan / Jinlei Zhang / Mengqi Chang / Liqin Liu / Hui Huang / Jie Lu / Wenrong Wu / Ruitong Chen / Shuyu Wu / Yibing Gao / Yujiao Cao / Hangtian Ding / Qingbing Zheng / Yingbin Wang / Quan Yuan / Hualong Xiong / Kegong Tian / Tianying Zhang / Ningshao Xia / 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 ...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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