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

Mol Ther. 2019 May 8;27(5):974-985. doi: 10.1016/j.ymthe.2019.03.005. Epub 2019 Apr 5.

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.

Keywords: DMAb; DNA; DNA-encoded monoclonal antibody; Zika virus; antibody; immunoprophylaxis; infectious diseases; protection; rhesus macaque.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / pharmacology*
  • Antibodies, Viral / immunology
  • Antibodies, Viral / pharmacology
  • DNA / immunology
  • DNA / pharmacology*
  • Humans
  • Mice
  • Primates
  • Viral Envelope Proteins / antagonists & inhibitors
  • Viral Envelope Proteins / immunology*
  • Zika Virus / genetics
  • Zika Virus / immunology
  • Zika Virus / pathogenicity
  • Zika Virus Infection / genetics*
  • Zika Virus Infection / immunology
  • Zika Virus Infection / therapy
  • Zika Virus Infection / virology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Viral Envelope Proteins
  • DNA