Cell Reports (Sep 2019)
A Gorilla Adenovirus-Based Vaccine against Zika Virus Induces Durable Immunity and Confers Protection in Pregnancy
Abstract
Summary: The teratogenic potential of Zika virus (ZIKV) has made the development of an effective vaccine a global health priority. Here, we generate two gorilla adenovirus-based ZIKV vaccines that encode for pre-membrane (prM) and envelope (E) proteins (GAd-Zvp) or prM and the ectodomain of E protein (GAd-Eecto). Both vaccines induce humoral and cell-mediated immune responses and prevent lethality after ZIKV challenge in mice. Protection is antibody dependent, CD8+ T cell independent, and for GAd-Eecto requires the complement component C1q. Immunization of GAd-Zvp induces antibodies against a key neutralizing epitope on domain III of E protein and confers durable protection as evidenced by memory B and long-lived plasma cell responses and challenge studies 9 months later. In two models of ZIKV infection during pregnancy, GAd-Zvp prevents maternal-to-fetal transmission. The gorilla adenovirus-based vaccine platform encoding full-length prM and E genes is a promising candidate for preventing congenital ZIKV syndrome and possibly infection by other flaviviruses. : Hassan et al. generate gorilla adenovirus vector vaccines against ZIKV that induce durable neutralizing antibody responses and protect mice against lethal ZIKV challenge. One of the vaccines, which encodes for virus-like particles, protects against in utero transmission of ZIKV in immunocompromised and immunocompetent pregnancy models in mice. Keywords: vaccine, Zika virus, flavivirus, adaptive immunity, pathogenesis, pregnancy