NS1 DNA vaccination protects against Zika infection through T cell-mediated immunity in immunocompetent mice.
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Date
2019
Authors
Grubor-Bauk, B.
Wijesundara, D.K.
Masavuli, M.
Abbink, P.
Peterson, R.L.
Prow, N.A.
Larocca, R.A.
Mekonnen, Z.A.
Shrestha, A.
Eyre, N.S.
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Science Advances, 2019; 5(12):eaax2388-eaax2388
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The causal association of Zika virus (ZIKV) with microcephaly, congenital malformations in infants, and Guillain-Barré syndrome in adults highlights the need for effective vaccines. Thus far, efforts to develop ZIKV vaccines have focused on the viral envelope. ZIKV NS1 as a vaccine immunogen has not been fully explored, although it can circumvent the risk of antibody-dependent enhancement of ZIKV infection, associated with envelope antibodies. Here, we describe a novel DNA vaccine encoding a secreted ZIKV NS1, that confers rapid protection from systemic ZIKV infection in immunocompetent mice. We identify novel NS1 T cell epitopes in vivo and show that functional NS1-specific T cell responses are critical for protection against ZIKV infection. We demonstrate that vaccine-induced anti-NS1 antibodies fail to confer protection in the absence of a functional T cell response. This highlights the importance of using NS1 as a target for T cell-based ZIKV vaccines.
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Copyright 2019 The Authors (https://creativecommons.org/licenses/by-nc/4.0/)