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NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice
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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905874/ https://www.ncbi.nlm.nih.gov/pubmed/31844662 http://dx.doi.org/10.1126/sciadv.aax2388 |
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author | 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. |
author_facet | 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. |
author_sort | Grubor-Bauk, B. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6905874 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-69058742019-12-16 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. Sci Adv Research Articles 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. American Association for the Advancement of Science 2019-12-11 /pmc/articles/PMC6905874/ /pubmed/31844662 http://dx.doi.org/10.1126/sciadv.aax2388 Text en Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles 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 |
title | NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice |
title_full | NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice |
title_fullStr | NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice |
title_full_unstemmed | NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice |
title_short | NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice |
title_sort | ns1 dna vaccination protects against zika infection through t cell–mediated immunity in immunocompetent mice |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905874/ https://www.ncbi.nlm.nih.gov/pubmed/31844662 http://dx.doi.org/10.1126/sciadv.aax2388 |
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