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

DNA 编码单克隆抗体的体内递送可保护非人类灵长类动物免受寨卡病毒的侵害

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作者:Rianne N Esquivel, Ami Patel, Sagar B Kudchodkar, Daniel H Park, Karin Stettler, Martina Beltramello, Jeffrey W Allen, Janess Mendoza, Stephanie Ramos, Hyeree Choi, Piyush Borole, Kanika Asija, Mamadou Bah, Shareef Shaheen, Jing Chen, Jian Yan, Amy C Durham, Trevor R F Smith, Kate Broderick, Ghiabe

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.

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