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In Vivo Delivery of a DNA-Encoded Monoclonal Antibody Protects Non-human Primates against Zika Virus

Authors :
Ghiabe Guibinga
Janess M. Mendoza
David B. Weiner
Laurent Humeau
Stephanie Ramos
Jian Yan
Sagar B. Kudchodkar
Trevor R.F. Smith
Kanika Asija
Jeffrey W. Allen
Piyush Borole
Jing Chen
Martina Beltramello
Ami Patel
Mamadou A. Bah
Karin Stettler
Davide Corti
Rianne Esquivel
Amy C. Durham
Hyeree Choi
Daniel H. Park
Shareef Shaheen
Kate E. Broderick
Karuppiah Muthumani
Source :
Molecular Therapy
Publication Year :
2019
Publisher :
Elsevier BV, 2019.

Abstract

Zika virus (ZIKV) infection is endemic to several world regions, and many others are at high risk for seasonal outbreaks. Synthetic DNA-encoded monoclonal antibody (DMAb) is an approach that enables in vivo delivery of highly potent mAbs to control infections. We engineered DMAb-ZK190, encoding the mAb ZK190 neutralizing antibody, which targets the ZIKV E protein DIII domain. In vivo-delivered DMAb-ZK190 achieved expression levels persisting >10 weeks in mice and >3 weeks in non-human primate (NHPs), which is protective against ZIKV infectious challenge. This study is the first demonstration of infectious disease control in NHPs following in vivo delivery of a nucleic acid-encoded antibody, supporting the importance of this new platform.<br />Esquivel et al. deliver DNA-encoded ZK190 antibody (DMAb-ZK190) by intramuscular administration. DMAb-ZK190 targets the E protein of Zika virus, and it controls Zika virus infection in mice and non-human primates when delivered prior to infection, offering an alternative strategy for rapid protection.

Details

ISSN :
15250016
Volume :
27
Database :
OpenAIRE
Journal :
Molecular Therapy
Accession number :
edsair.doi.dedup.....133a453f4a05cc225e8fa2a84bcc76ca
Full Text :
https://doi.org/10.1016/j.ymthe.2019.03.005