Zika: a safe recombinant vaccine with proof of efficacy in rodents

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We will construct a recombinant modified vaccinia Ankara (MVA) Zika virus vaccine in Manchester, and obtain proof of protection in a rodent model of Zika infection under development at Porton Down.
Recombinant modified vaccinia Ankara has been widely used as a human vaccine candidate. MVA has an excellent safety record, does not replicate in mammals, has a desirable cytokine receptor profile, and is particularly immunogenic when employed as a boosting agent(1-3). Such a vaccine would be suitable for large-scale use across whole populations giving simultaneous protection whilst interrupting the transmission of Zika.
Recombinant MVA has already been employed to generate vaccine candidates for related flaviviruses such as Japanese B encephalitis virus (JEV) and dengue(4-6). These employ prM and E sequences, sometimes truncated. We will employ capsid sequences as well, in order to generate more immunogenic virus-like particles. Recombinant vaccines such as these may be difficult to generate because of syncytia formation in which case strategies such as T7 expression system regulated by coinfection will be employed.
Licensed vaccines for the closely related dengue virus and for JEV do exist. In the case of the Sanofi-Pasteur dengue vaccine this is based on recombinant variants of the 17D yellow fever vaccine: there would be concern that an equivalent Zika vaccine might be embryotoxic. The JEV vaccine is an inactivated derivative of JEV: manufacture of such a vaccine would require large scale production of Zika (not possible at present) and always carries the risk of environmental release or failure of inactivation.