A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates

Cell Rep. 2018 Nov 6;25(6):1385-1394.e7. doi: 10.1016/j.celrep.2018.10.031.

Abstract

Zika virus (ZIKV) causes severe neurologic complications and fetal aberrations. Vaccine development is hindered by potential safety concerns due to antibody cross-reactivity with dengue virus and the possibility of disease enhancement. In contrast, passive administration of anti-ZIKV antibodies engineered to prevent enhancement may be safe and effective. Here, we report on human monoclonal antibody Z021, a potent neutralizer that recognizes an epitope on the lateral ridge of the envelope domain III (EDIII) of ZIKV and is protective against ZIKV in mice. When administered to macaques undergoing a high-dose ZIKV challenge, a single anti-EDIII antibody selected for resistant variants. Co-administration of two antibodies, Z004 and Z021, which target distinct sites on EDIII, was associated with a delay and a 3- to 4-log decrease in peak viremia. Moreover, the combination of these antibodies engineered to avoid enhancement prevented viral escape due to mutation in macaques, a natural host for ZIKV.

Keywords: antibodies; antibody dependent enhancement; crystal structure; epitope; escape; flavivirus; macaques; prophylaxis; protection.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Neutralizing / immunology
  • Dengue Virus / immunology
  • Epitopes / immunology
  • HEK293 Cells
  • Humans
  • Macaca
  • Mice, Knockout
  • Mutation / genetics*
  • Protein Domains
  • Zika Virus / immunology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Epitopes