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Nat Med. 2017 Jun;23(6):763-767. doi: 10.1038/nm.4322. Epub 2017 Apr 10.

A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models.

Author information

1
Department of Biochemistry &Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA.
2
Institute for Human Infections &Immunity, University of Texas Medical Branch, Galveston, Texas, USA.
3
Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas, USA.
4
Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Ministry of Health, Ananindeua, Pará State, Brazil.
5
Department of Microbiology &Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
6
Department of Pathology and Center for Biodefense &Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA.
7
Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA.
8
Sealy Center for Structural Biology &Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas, USA.
9
Department of Pathology, Pará State University, Belém, Brazil.
10
Department of Phamarcology &Toxicology, University of Texas Medical Branch, Galveston, Texas, USA.

Abstract

Zika virus (ZIKV) infection of pregnant women can cause a wide range of congenital abnormalities, including microcephaly, in the infant, a condition now collectively known as congenital ZIKV syndrome. A vaccine to prevent or significantly attenuate viremia in pregnant women who are residents of or travelers to epidemic or endemic regions is needed to avert congenital ZIKV syndrome, and might also help to suppress epidemic transmission. Here we report on a live-attenuated vaccine candidate that contains a 10-nucleotide deletion in the 3' untranslated region of the ZIKV genome (10-del ZIKV). The 10-del ZIKV is highly attenuated, immunogenic, and protective in type 1 interferon receptor-deficient A129 mice. Crucially, a single dose of 10-del ZIKV induced sterilizing immunity with a saturated neutralizing antibody titer, which no longer increased after challenge with an epidemic ZIKV, and completely prevented viremia. The immunized mice also developed a robust T cell response. Intracranial inoculation of 1-d-old immunocompetent CD-1 mice with 1 × 104 infectious focus units (IFU) of 10-del ZIKV caused no mortality, whereas infections with 10 IFU of wild-type ZIKV were lethal. Mechanistically, the attenuated virulence of 10-del ZIKV may be due to decreased viral RNA synthesis and increased sensitivity to type-1-interferon inhibition. The attenuated 10-del ZIKV was incapable of infecting mosquitoes after oral feeding of spiked-blood meals, representing an additional safety feature. Collectively, the safety and efficacy results suggest that further development of this promising, live-attenuated ZIKV vaccine candidate is warranted.

Comment in

PMID:
28394328
PMCID:
PMC6276361
DOI:
10.1038/nm.4322
[Indexed for MEDLINE]
Free PMC Article

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