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

24 Oct 2025
Yue M, Zhu Y, Wu H, Yan S, Zhang J, Chang M, Liu L, Huang H, Lu J, Wu W, Chen R, Wu S, Gao Y, Cao Y, Ding H, Zheng Q, Wang Y, Yuan Q, Xiong H, Tian K, Zhang T, Xia N
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.