Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

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

In another approach, the attenuated VSV-EBOV was used as a vector to express ZprME or prM and soluble envelope proteins as antigens (ZprMsolE) and efficacy was tested in type I interferon receptor deficient mice (IFNAR − / − ). The ZIKV vaccine candidates did not result in pathogenicity in mice, however, unexpectedly vaccination with VSV-EBOV control vector led to severe clinical symptoms in the immunocompromised mice, thus the VSV-EBOV-based ZIKV vaccine constructs appear to be more attenuated than the original VSV-EBOV in this study. Mice challenged with ZIKV 28 days p.v. were fully protected from disease. Antigenicity of ZprME seemed to be superior to ZprMsolE and 50% and 100% protection was achieved when mice were vaccinated with rVSV-ZprME 1 and 3 days pre-challenge, respectively. Interestingly, vaccination with the vaccines was sufficient to also protect outbred CD1 mice from EBOV challenge. 123 In a study assessing multiple ZIKV antigens in a VSV vector, which was attenuated via a point mutation in the VSV L protein, combining the ZIKV prM and E proteins with the nonstructural NS1 protein showed robust humoral and cellular responses in immunocompetent mice, as well as protection from disease in IFNAR − / − mice. 124 Furthermore, a VSV vector expressing the ZIKV capsid protein was also shown to be immunogenic with dominating cellular immune responses and reduced viral replication in the spinal cord and brain tissues of immunocompetent mice. 125 No human clinical trials using VSV-based ZIKV vaccine candidates have been initiated to date.