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

Abstract

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.

Authors:
ORCiD logo [1];  [1]; ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [2]; ORCiD logo [3]; ORCiD logo [2]; ORCiD logo [1];  [1]; ORCiD logo [4]; ORCiD logo [4];  [4]; ORCiD logo [5]; ORCiD logo [4]; ORCiD logo [6]; ORCiD logo [7]; ORCiD logo [1]
  1. Univ. of Adelaide, SA (Australia); Basil Hetzel Inst. for Translational Health Research, Adelaide, SA (Australia)
  2. Harvard Medical School, Boston, MA (United States)
  3. Univ. of South Australia, Adelaide, SA (Australia); QIMR Berghofer Medical Research Inst., Brisbane, QLD (Australia); Australian Infectious Diseases Research Centre, Brisbane, QLD (Australia)
  4. Univ. of Adelaide, SA (Australia)
  5. Finders Univ., Adelaide, SA (Australia)
  6. Univ. of South Australia, Adelaide, SA (Australia); Univ. of Adelaide, SA (Australia)
  7. Harvard Medical School, Boston, MA (United States); Ragon Inst. of MGH, MIT, and Harvard, Cambridge, MA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1591849
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Science Advances
Additional Journal Information:
Journal Volume: 5; Journal Issue: 12; Journal ID: ISSN 2375-2548
Publisher:
AAAS
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

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., and Gowans, E. J. NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice. United States: N. p., 2019. Web. doi:10.1126/sciadv.aax2388.
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. NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice. United States. doi:10.1126/sciadv.aax2388.
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., and Gowans, E. J. Wed . "NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice". United States. doi:10.1126/sciadv.aax2388. https://www.osti.gov/servlets/purl/1591849.
@article{osti_1591849,
title = {NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice},
author = {Grubor-Bauk, B. and Wijesundara, D. K. and Masavuli, M. and Abbink, P. and Peterson, R. L. and Prow, N. A. and Larocca, R. A. and Mekonnen, Z. A. and Shrestha, A. and Eyre, N. S. and Beard, M. R. and Gummow, J. and Carr, J. and Robertson, S. A. and Hayball, J. D. and Barouch, D. H. and Gowans, E. J.},
abstractNote = {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.},
doi = {10.1126/sciadv.aax2388},
journal = {Science Advances},
number = 12,
volume = 5,
place = {United States},
year = {2019},
month = {12}
}

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