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A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model

Zika virus (ZIKV) is a mosquito-borne flavivirus that has rapidly extended its geographic range around the world. Its association with abnormal fetal brain development, sexual transmission, and lack of a preventive vaccine have constituted a global health concern. Designing a safe and effective vacc...

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Autores principales: Brault, Aaron C., Domi, Arban, McDonald, Erin M., Talmi-Frank, Dalit, McCurley, Nathanael, Basu, Rahul, Robinson, Harriet L., Hellerstein, Michael, Duggal, Nisha K., Bowen, Richard A., Guirakhoo, Farshad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677088/
https://www.ncbi.nlm.nih.gov/pubmed/29116169
http://dx.doi.org/10.1038/s41598-017-15039-8
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author Brault, Aaron C.
Domi, Arban
McDonald, Erin M.
Talmi-Frank, Dalit
McCurley, Nathanael
Basu, Rahul
Robinson, Harriet L.
Hellerstein, Michael
Duggal, Nisha K.
Bowen, Richard A.
Guirakhoo, Farshad
author_facet Brault, Aaron C.
Domi, Arban
McDonald, Erin M.
Talmi-Frank, Dalit
McCurley, Nathanael
Basu, Rahul
Robinson, Harriet L.
Hellerstein, Michael
Duggal, Nisha K.
Bowen, Richard A.
Guirakhoo, Farshad
author_sort Brault, Aaron C.
collection PubMed
description Zika virus (ZIKV) is a mosquito-borne flavivirus that has rapidly extended its geographic range around the world. Its association with abnormal fetal brain development, sexual transmission, and lack of a preventive vaccine have constituted a global health concern. Designing a safe and effective vaccine requires significant caution due to overlapping geographical distribution of ZIKV with dengue virus (DENV) and other flaviviruses, possibly resulting in more severe disease manifestations in flavivirus immune vaccinees such as Antibody-Dependent Enhancement (ADE, a phenomenon involved in pathogenesis of DENV, and a risk associated with ZIKV vaccines using the envelope proteins as immunogens). Here, we describe the development of an alternative vaccine strategy encompassing the expression of ZIKV non-structural-1 (NS1) protein from a clinically proven safe, Modified Vaccinia Ankara (MVA) vector, thus averting the potential risk of ADE associated with structural protein-based ZIKV vaccines. A single intramuscular immunization of immunocompetent mice with the MVA-ZIKV-NS1 vaccine candidate provided robust humoral and cellular responses, and afforded 100% protection against a lethal intracerebral dose of ZIKV (strain MR766). This is the first report of (i) a ZIKV vaccine based on the NS1 protein and (ii) single dose protection against ZIKV using an immunocompetent lethal mouse challenge model.
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spelling pubmed-56770882017-11-15 A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model Brault, Aaron C. Domi, Arban McDonald, Erin M. Talmi-Frank, Dalit McCurley, Nathanael Basu, Rahul Robinson, Harriet L. Hellerstein, Michael Duggal, Nisha K. Bowen, Richard A. Guirakhoo, Farshad Sci Rep Article Zika virus (ZIKV) is a mosquito-borne flavivirus that has rapidly extended its geographic range around the world. Its association with abnormal fetal brain development, sexual transmission, and lack of a preventive vaccine have constituted a global health concern. Designing a safe and effective vaccine requires significant caution due to overlapping geographical distribution of ZIKV with dengue virus (DENV) and other flaviviruses, possibly resulting in more severe disease manifestations in flavivirus immune vaccinees such as Antibody-Dependent Enhancement (ADE, a phenomenon involved in pathogenesis of DENV, and a risk associated with ZIKV vaccines using the envelope proteins as immunogens). Here, we describe the development of an alternative vaccine strategy encompassing the expression of ZIKV non-structural-1 (NS1) protein from a clinically proven safe, Modified Vaccinia Ankara (MVA) vector, thus averting the potential risk of ADE associated with structural protein-based ZIKV vaccines. A single intramuscular immunization of immunocompetent mice with the MVA-ZIKV-NS1 vaccine candidate provided robust humoral and cellular responses, and afforded 100% protection against a lethal intracerebral dose of ZIKV (strain MR766). This is the first report of (i) a ZIKV vaccine based on the NS1 protein and (ii) single dose protection against ZIKV using an immunocompetent lethal mouse challenge model. Nature Publishing Group UK 2017-11-07 /pmc/articles/PMC5677088/ /pubmed/29116169 http://dx.doi.org/10.1038/s41598-017-15039-8 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Brault, Aaron C.
Domi, Arban
McDonald, Erin M.
Talmi-Frank, Dalit
McCurley, Nathanael
Basu, Rahul
Robinson, Harriet L.
Hellerstein, Michael
Duggal, Nisha K.
Bowen, Richard A.
Guirakhoo, Farshad
A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title_full A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title_fullStr A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title_full_unstemmed A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title_short A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title_sort zika vaccine targeting ns1 protein protects immunocompetent adult mice in a lethal challenge model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677088/
https://www.ncbi.nlm.nih.gov/pubmed/29116169
http://dx.doi.org/10.1038/s41598-017-15039-8
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