title: Vaccine protection against Zika virus from Brazil.
abstract: Zika virus (ZIKV) is a flavivirus that is responsible for the current epidemic in Brazil and the Americas. ZIKV has been causally associated with fetal microcephaly, intrauterine growth restriction, and other birth defects in both humans and mice. The rapid development of a safe and effective ZIKV vaccine is a global health priority, but very little is currently known about ZIKV immunology and mechanisms of immune protection. Here we show that a single immunization with a plasmid DNA vaccine or a purified inactivated virus vaccine provides complete protection in susceptible mice against challenge with a strain of ZIKV involved in the outbreak in northeast Brazil. This ZIKV strain has recently been shown to cross the placenta and to induce fetal microcephaly and other congenital malformations in mice. We produced DNA vaccines expressing ZIKV pre-membrane and envelope (prM-Env), as well as a series of deletion mutants. The prM-Env DNA vaccine, but not the deletion mutants, afforded complete protection against ZIKV, as measured by absence of detectable viraemia following challenge, and protective efficacy correlated with Env-specific antibody titers. Adoptive transfer of purified IgG from vaccinated mice conferred passive protection, and depletion of CD4 and CD8 T lymphocytes in vaccinated mice did not abrogate this protection. 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 is likely to be achievable.
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Larocca
authors.forename: Peter
authors.initials: P
authors.lastname: Abbink
authors.forename: Jean Pierre S
authors.initials: JP
authors.lastname: Peron
authors.forename: Paolo M de A
authors.initials: PM
authors.lastname: Zanotto
authors.forename: M Justin
authors.initials: MJ
authors.lastname: Iampietro
authors.forename: Alexander
authors.initials: A
authors.lastname: Badamchi-Zadeh
authors.forename: Michael
authors.initials: M
authors.lastname: Boyd
authors.forename: David
authors.initials: D
authors.lastname: Ng'ang'a
authors.forename: Marinela
authors.initials: M
authors.lastname: Kirilova
authors.forename: Ramya
authors.initials: R
authors.lastname: Nityanandam
authors.forename: Noe B
authors.initials: NB
authors.lastname: Mercado
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Li
authors.forename: Edward T
authors.initials: ET
authors.lastname: Moseley
authors.forename: Christine A
authors.initials: CA
authors.lastname: Bricault
authors.forename: Erica N
authors.initials: EN
authors.lastname: Borducchi
authors.forename: Patricia B
authors.initials: PB
authors.lastname: Giglio
authors.forename: David
authors.initials: D
authors.lastname: Jetton
authors.forename: George
authors.initials: G
authors.lastname: Neubauer
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Nkolola
authors.forename: Lori F
authors.initials: LF
authors.lastname: Maxfield
authors.forename: Rafael A
authors.initials: RA
authors.lastname: De La Barrera
authors.forename: Richard G
authors.initials: RG
authors.lastname: Jarman
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Eckels
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Thomas
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000918:Antibody Specificity; D001938:Brazil; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000302:isolation & purification; D051379:Mice; D008831:Microcephaly / Q000150:complications / Q000821:virology; D019444:Vaccines, DNA / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015164:Vaccines, Inactivated / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D022223:Vaccines, Subunit / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000071244:Zika Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000071243:Zika Virus Infection / Q000150:complications / Q000276:immunology / Q000517:prevention & control* / Q000821:virology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D015164:Vaccines, Inactivated; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; D014765:Viral Vaccines