A combination of two human monoclonal antibodies limits fetal damage by Zika virus in macaques

Proc Natl Acad Sci U S A. 2020 Apr 7;117(14):7981-7989. doi: 10.1073/pnas.2000414117. Epub 2020 Mar 24.

Abstract

Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement (ADE) in vitro and extend their half-lives. Here we report on prophylactic coadministration of the Fc-modified antibodies to pregnant rhesus macaques challenged three times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission, protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV.

Keywords: Fc domain modifications; Zika virus; antibody-dependent enhancement; congenital Zika syndrome; macaque pregnancy model.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / administration & dosage
  • Antibodies, Neutralizing / genetics
  • Antibodies, Neutralizing / immunology
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Female
  • Fetus / immunology
  • Fetus / virology
  • HEK293 Cells
  • Humans
  • Immunoglobulin Fc Fragments / administration & dosage
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin Fc Fragments / immunology
  • Immunoglobulin G / administration & dosage
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology
  • Infectious Disease Transmission, Vertical / prevention & control*
  • Pregnancy
  • Pregnancy Complications, Infectious / immunology
  • Pregnancy Complications, Infectious / prevention & control*
  • Pregnancy Complications, Infectious / virology
  • Protein Engineering
  • RNA, Viral / isolation & purification
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Zika Virus / genetics
  • Zika Virus / immunology*
  • Zika Virus / pathogenicity
  • Zika Virus Infection / immunology
  • Zika Virus Infection / prevention & control*
  • Zika Virus Infection / transmission
  • Zika Virus Infection / virology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • RNA, Viral
  • Recombinant Proteins