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

Aaron Brault, Arban Domi, Erin M. McDonald, Dalit Talmi-Frank, Nathanael McCurley, Rahul Basu, Harriet L. Robinson, Michael Hellerstein, Nisha K. Duggal, Richard A. Bowen, Farshad Guirakhoo

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number14769
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

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Vaccines
Flavivirus
Proteins
Vaccinia
Dengue Virus
Antibody-Dependent Enhancement
Zika Virus
Fetal Development
Culicidae
Immunization
Brain

ASJC Scopus subject areas

  • General

Cite this

Brault, A., Domi, A., McDonald, E. M., Talmi-Frank, D., McCurley, N., Basu, R., ... Guirakhoo, F. (2017). A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model. Scientific Reports, 7(1), [14769]. https://doi.org/10.1038/s41598-017-15039-8

A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model. / Brault, Aaron; 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.

In: Scientific Reports, Vol. 7, No. 1, 14769, 01.12.2017.

Research output: Contribution to journalArticle

Brault, A, Domi, A, McDonald, EM, Talmi-Frank, D, McCurley, N, Basu, R, Robinson, HL, Hellerstein, M, Duggal, NK, Bowen, RA & Guirakhoo, F 2017, 'A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model', Scientific Reports, vol. 7, no. 1, 14769. https://doi.org/10.1038/s41598-017-15039-8
Brault, Aaron ; 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. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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