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.