Vaccine protection against Zika virus from Brazil

• Published in: Nature (London) Vol. 536; no. 7617; pp. 474 - 478
• Main Authors: Larocca, Rafael A., Abbink, Peter, Peron, Jean Pierre S., de A. Zanotto, Paolo M., Iampietro, M. Justin, Badamchi-Zadeh, Alexander, Boyd, Michael, Ng’ang’a, David, Kirilova, Marinela, Nityanandam, Ramya, Mercado, Noe B., Li, Zhenfeng, Moseley, Edward T., Bricault, Christine A., Borducchi, Erica N., Giglio, Patricia B., Jetton, David, Neubauer, George, Nkolola, Joseph P., Maxfield, Lori F., De La Barrera, Rafael A., Jarman, Richard G., Eckels, Kenneth H., Michael, Nelson L., Thomas, Stephen J., Barouch, Dan H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.08.2016; Nature Publishing Group
• Subjects: 631/250/590; 631/326/596; Adoptive Transfer; Animals; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antibody Specificity; Birth defects; Brazil; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Deoxyribonucleic acid; Distribution; DNA; Dosage and administration; Encephalitis; Epidemics; Female; Fetuses; Gene Deletion; Global health; Humanities and Social Sciences; Humans; Immunization; Immunoglobulin G - immunology; Immunoglobulin G - isolation & purification; Immunology; letter; Mice; Microcephaly; Microcephaly - complications; Microcephaly - virology; multidisciplinary; Prevention; Product development; Science; Studies; Testing; Vaccines; Vaccines, DNA - chemistry; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Vaccines, Inactivated - chemistry; Vaccines, Inactivated - genetics; Vaccines, Inactivated - immunology; Vaccines, Subunit - chemistry; Vaccines, Subunit - genetics; Vaccines, Subunit - immunology; Vector-borne diseases; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viral vaccines; Viral Vaccines - chemistry; Viral Vaccines - genetics; Viral Vaccines - immunology; Zika virus; Zika Virus - chemistry; Zika Virus - genetics; Zika Virus - immunology; Zika virus infection; Zika Virus Infection - complications; Zika Virus Infection - immunology; Zika Virus Infection - prevention & control; Zika Virus Infection - virology; Brazil; Puerto Rico
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature18952

The authors test several candidate vaccines for Zika virus in mouse models and show that single-shot DNA vaccines and inactivated virus vaccines provide complete protection against Zika virus isolates from Brazil and Puerto Rico. A vaccine effective against Zika virus Dan Barouch and colleagues explore candidate vaccines for Zika virus in mouse models and show that single-shot DNA vaccines and inactivated virus vaccine provide complete protection against Zika virus isolates from Brazil and Puerto Rico. Protection correlates with Env-specific antibody titres and can be passively transferred. Zika virus (ZIKV) is a flavivirus that is responsible for the 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 , 4 , 5 , 6 , 7 , 8 and mice 9 , 10 , 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 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 11 . 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.