Rafael A. Larocca 1 , Peter Abbink 1 , Jean Pierre S. Peron 2 , Paolo M. de A. Zanotto 2 , M. Justin Iampietro 1 , Alexander Badamchi-Zadeh 1 , Michael Boyd 1 , David Ng’ang’a 1 , Marinela Kirilova 1 , Ramya Nityanandam 1 , Noe B. Mercado 1 , Zhenfeng Li 1 , Edward T. Moseley 1 , Christine A. Bricault 1 , Erica N. Borducchi 1 , Patricia B. Giglio 1 , David Jetton 1 , George Neubauer 1 , Joseph P. Nkolola 1 , Lori F. Maxfield 1 , Rafael A. De La Barrera 3 , Richard G. Jarman 3 , Kenneth H. Eckels 3 , Nelson L. Michael 3 , Stephen J. Thomas 3 , Dan H. Barouch 1 , 4 , **
25 February 2017
Zika virus (ZIKV) is a flavivirus that is responsible for an unprecedented current epidemic in Brazil and the Americas 1, 2 . ZIKV has been causally associated with fetal microcephaly, intrauterine growth restriction, and other birth defects in both humans 3– 8 and mice 9– 11 . The rapid development of a safe and effective ZIKV vaccine is a global health priority 1, 2 , but very little is currently known about ZIKV immunology and mechanisms of immune protection. Here we show that a single immunization of a plasmid DNA vaccine or a purified inactivated virus vaccine provides complete protection in susceptible mice against challenge with a ZIKV outbreak strain from northeast Brazil. This ZIKV strain has recently been shown to cross the placenta and to induce fetal microcephaly and other congenital malformations in mice 11 . We produced DNA vaccines expressing full-length ZIKV pre-membrane and envelope (prM-Env) as well as a series of deletion mutants. The full-length prM-Env DNA vaccine, but not the deletion mutants, afforded complete protection against ZIKV as measured by absence of detectable viremia following challenge, and protective efficacy correlated with Env-specific antibody titers. Adoptive transfer of purified IgG from vaccinated mice conferred passive protection, and CD4 and CD8 T lymphocyte depletion in vaccinated mice did not abrogate protective efficacy. These data demonstrate that protection against ZIKV challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection. Our findings suggest that the development of a ZIKV vaccine for humans will likely be readily achievable.