Development of a ZIKA viral pseudoinfectious virus as ZIKA vaccine candidate (STTR Phase II)

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Development of Zika viral pseudoinfectious virus as zika vaccine candidate (Phase 2) Abstract Zika virus epidemics and the association of ZIKV infection with Guillain–Barré syndrome, and congenital disabilities, including microcephaly, led the World Health Organization to declare ZIKV a “Public Health Emergency of International Concern” in 2016. Since then, various ZIKV vaccine platforms have been developed to control future epidemics. Historically, live-attenuated viral vaccines induce long-lasting protective immunity but reduced safety, whereas inactivated vaccines provide a high level of initial protection but exhibit weak long-term immunity. Third generation encapsidation-defective flavivirus vaccines have demonstrated surprisingly potent with high level of safety in animal models. However, they need complicated packaging systemor helper viral replicons, which make a licenced commercial production difficult and costly. Recently, we have converted a dual-host ZIKV into a vertebrate-specific replication defective ZIKV (VSRD-ZIKV; Wan et al in press) which can be efficiently produced at relatively low cost. In our phase 1 studies, we characterized the safety and efficacy of VSRD-ZIKV in a murine model. In the proposed phase 2 studies, we propose to: 1) study the genotypic and phenotypic stability of VSRD-ZIKV during culturing on manufacture cell substrate; 2) develop a seed lot stock; 3) evaluate the safety and efficacy of VSRD-ZIKV in a non-human primate model. By completing these goals we hope to produce a vaccine with a high safety and immunogenicity profile that could be moved toward human clinical trials. To achieve these goals we have established an experienced team. A strong partnership exists between the Howard University and Tengen. In addition, both groups will work closely with experts in Bioqual Inc who will be conducting the NHP trial.