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.
Grubor-Bauk, B., et al. "NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice." Science Advances, vol. 5, no. 12, Dec. 2019. https://doi.org/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. (2019). NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice. Science Advances, 5(12). https://doi.org/10.1126/sciadv.aax2388
Grubor-Bauk, B., Wijesundara, D. K., Masavuli, M., et al., "NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice," Science Advances 5, no. 12 (2019), https://doi.org/10.1126/sciadv.aax2388
@article{osti_1591849,
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 others},
title = {NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice},
annote = {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},
url = {https://www.osti.gov/biblio/1591849},
journal = {Science Advances},
issn = {ISSN 2375-2548},
number = {12},
volume = {5},
place = {United States},
publisher = {AAAS},
year = {2019},
month = {12}}