A Zika vaccine based on chimpanzee adenovirus ChAdOx1 elicits lineage-transcending sterile immunity and prevents colonisation of brain and ovaries

Zika virus (ZIKV) continuous spread has affected more than 80 countries and no licenced vaccine is currently available. The Asian-lineage is the causative agent of major outbreaks across the globe and most of the current ZIKV vaccine candidates aim to provide homologous efficacy in ZIKV pre-clinical challenge models. In contrast, the African-lineage of ZIKV is mainly restricted to sylvatic transmission but not much is known about the ability of this virus to emerge from a sylvatic to human transmission. Efficacy of ZIKV vaccine in mice or macaques relies on the quantification of viraemia by RT-PCR. However, questions remain as to whether current ZIKV vaccine candidates offer lineage-transcending protection and viral clearance in key organs, such as the brain and reproductive tract. Here, we show the cross-protective capabilities of our previously reported simian adenoviral-vectored zika vaccines (ChAdOx1 ZIKV) against a heterologous African-ZIKV challenge model, in which A129 mice display a high susceptibility to ZIKV infection. Furthermore, we have assessed the ability of our vaccines to prevent infection in tissues such as the brain and ovaries, as both tissues are relevant for ZIKV pathogenesis. Finally, we describe a novel ChAdOx1 ZIKV vaccine design carrying a consensus antigen of the African-ZIKV lineage and tested its efficacy in a homologous challenge model.