NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice

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.; Beard, M. R.; Gummow, J.; Carr, J.; Robertson, S. A.; Hayball, J. D.; Barouch, D. H.; Gowans, E. J.

doi:10.1126/sciadv.aax2388

Title: NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice

Journal Article · 11 December 2019 · Science Advances

DOI: https://doi.org/10.1126/sciadv.aax2388 · OSTI ID:1591849

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Univ. of Adelaide, SA (Australia); Basil Hetzel Inst. for Translational Health Research, Adelaide, SA (Australia)
Harvard Medical School, Boston, MA (United States)
Univ. of South Australia, Adelaide, SA (Australia); QIMR Berghofer Medical Research Inst., Brisbane, QLD (Australia); Australian Infectious Diseases Research Centre, Brisbane, QLD (Australia)
Univ. of Adelaide, SA (Australia)
Finders Univ., Adelaide, SA (Australia)
Univ. of South Australia, Adelaide, SA (Australia); Univ. of Adelaide, SA (Australia)
Harvard Medical School, Boston, MA (United States); Ragon Inst. of MGH, MIT, and Harvard, Cambridge, MA (United States)

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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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1591849

Journal Information:: Science Advances, Journal Name: Science Advances Journal Issue: 12 Vol. 5; ISSN 2375-2548

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: English

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Two Is Better Than One: Evidence for T-Cell Cross-Protection Between Dengue and Zika and Implications on Vaccine Design Subramaniam, Krishanthi S.; Lant, Suzannah; Goodwin, Lynsey Frontiers in Immunology, Vol. 11 https://doi.org/10.3389/fimmu.2020.00517	journal	March 2020
Zika Virus Inhibits IFN-α Response by Human Plasmacytoid Dendritic Cells and Induces NS1-Dependent Triggering of CD303 (BDCA-2) Signaling Bos, Sandra; Poirier-Beaudouin, Béatrice; Seffer, Valérie Frontiers in Immunology, Vol. 11 https://doi.org/10.3389/fimmu.2020.582061	journal	October 2020

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