Vaccine protection against Zika virus from Brazil.

TitleVaccine protection against Zika virus from Brazil.
Publication TypeJournal Article
Year of Publication2016
AuthorsLarocca RA, Abbink P, Peron JPierre S, Zanotto PM de A, Iampietro JM, Badamchi-Zadeh A, Boyd M, Ng'ang'a D, Kirilova M, Nityanandam R, Mercado NB, Li Z, Moseley ET, Bricault CA, Borducchi EN, Giglio PB, Jetton D, Neubauer G, Nkolola JP, Maxfield LF, De La Barrera RA, Jarman RG, Eckels KH, Michael NL, Thomas SJ, Barouch DH
JournalNature
Date Published08/25/2016
ISSN1476-4687
Abstract

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.

DOI10.1038/nature18952
Alternate JournalNature
PubMed ID27355570
Grant ListU19 AI095985 / AI / NIAID NIH HHS / United States
U19 AI096040 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
UM1 AI124377 / AI / NIAID NIH HHS / United States
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