Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice

Nature. 2016 Dec 15;540(7633):443-447. doi: 10.1038/nature20564. Epub 2016 Nov 7.

Abstract

Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe disease, including congenital birth defects during pregnancy. To develop candidate therapeutic agents against ZIKV, we isolated a panel of human monoclonal antibodies from subjects that were previously infected with ZIKV. We show that a subset of antibodies recognize diverse epitopes on the envelope (E) protein and exhibit potent neutralizing activity. One of the most inhibitory antibodies, ZIKV-117, broadly neutralized infection of ZIKV strains corresponding to African and Asian-American lineages. Epitope mapping studies revealed that ZIKV-117 recognized a unique quaternary epitope on the E protein dimer-dimer interface. We evaluated the therapeutic efficacy of ZIKV-117 in pregnant and non-pregnant mice. Monoclonal antibody treatment markedly reduced tissue pathology, placental and fetal infection, and mortality in mice. Thus, neutralizing human antibodies can protect against maternal-fetal transmission, infection and disease, and reveal important determinants for structure-based rational vaccine design efforts.

Publication types

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

MeSH terms

  • Africa
  • Americas
  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / therapeutic use
  • Antibodies, Viral / chemistry
  • Antibodies, Viral / immunology
  • Antibodies, Viral / therapeutic use
  • Antibody Specificity
  • Asia
  • B-Lymphocytes / immunology
  • Disease Models, Animal
  • Epitope Mapping
  • Female
  • Fetal Diseases / immunology
  • Fetal Diseases / prevention & control*
  • Fetal Diseases / virology
  • Fetus / immunology
  • Fetus / virology
  • Humans
  • Infectious Disease Transmission, Vertical / prevention & control*
  • Male
  • Mice
  • Models, Molecular
  • Placenta / immunology
  • Placenta / virology
  • Pregnancy
  • Protein Multimerization
  • Survival Rate
  • Viral Proteins / chemistry
  • Viral Proteins / immunology
  • Viral Vaccines / chemistry
  • Viral Vaccines / immunology
  • Virus Replication / immunology*
  • Zika Virus / growth & development*
  • Zika Virus / immunology*
  • Zika Virus Infection / immunology*
  • Zika Virus Infection / pathology
  • Zika Virus Infection / virology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Viral Proteins
  • Viral Vaccines