Ad26.M.Env ZIKV vaccine protects pregnant rhesus macaques and fetuses against Zika virus infection

At the start of the Zika virus (ZIKV) epidemic in 2015, ZIKV spread across South and Central America, and reached parts of the southern United States placing pregnant women at risk for fetal microcephaly, fetal loss, and other adverse pregnancy outcomes associated with congenital ZIKA syndrome (CZS). For this reason, testing of a safe and efficacious ZIKV vaccine remains a global health priority. Here we report that a single immunization with Ad26.M.Env ZIKV vaccine, when administered prior to conception, fully protects pregnant rhesus macaques from ZIKV viremia in blood and tissues with no adverse effects in dams and fetuses. Furthermore, vaccination prevents ZIKV distribution in fetal tissues including brain. ZIKV associated neuropathology was absent in offspring of Ad26.M.Env vaccinated dams, although pathology was limited in sham vaccinated controls. Vaccine efficacy is associated with induction of ZIKV neutralizing antibodies in pregnant rhesus macaques. A Phase I trial showed that Ad26.M.Env (Ad26.ZIKV.001) was safe and immunogenic in people. These data suggest the feasibility of vaccine prevention of ZCS in humans.