Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

Fathi, Anahita; Dahlke, Christine; Addo, Marylyn M.

A commonly used VSV vaccine design strategy utilizes an rVSV vector lacking VSV-G -rVSVΔGwhich is modified to encode the glycoprotein (GP) of the pathogen of interest in replacement of VSV-G, expressing the foreign GP on the viral membrane. 15 Besides being an efficient and stable way to insert antigens of interest, this approach holds two major advantages. It serves as an attenuation factor, as the pathogenicity of wild-type VSV has largely been attributed to VSV-G. An exchange of glycoproteins may affect cell-tropism and, therefore, additionally, attenuate the vaccine candidate. 14, 16, 17 Toxicity and pathogenicity are thereby significantly decreased leading to a more benign safety profile. Simultaneously, antibody responses to wild-type VSV are mostly directed against VSV-G in humans and, therefore, eliminating VSV-G is an efficient way to significantly reduce preexisting vector-specific immunity. 18 It, however, needs to be considered that rVSV is a replication competent vector and that vulnerable populations including immunocompromised individuals, pregnant women, infants and the elderly may be at higher risk for adverse events.