Structural basis of a potent human monoclonal antibody against Zika virus targeting a quaternary epitope

Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1591-1596. doi: 10.1073/pnas.1815432116. Epub 2019 Jan 14.


Zika virus (ZIKV) is a major human pathogen and member of the Flavivirus genus in the Flaviviridae family. In contrast to most other insect-transmitted flaviviruses, ZIKV also can be transmitted sexually and from mother to fetus in humans. During recent outbreaks, ZIKV infections have been linked to microcephaly, congenital disease, and Guillain-Barré syndrome. Neutralizing antibodies have potential as therapeutic agents. We report here a 4-Å-resolution cryo-electron microscopy structure of the ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195. The footprint of the ZIKV-195 Fab fragment expands across two adjacent envelope (E) protein protomers. ZIKV neutralization by this antibody is presumably accomplished by cross-linking the E proteins, which likely prevents formation of E protein trimers required for fusion of the viral and cellular membranes. A single dose of ZIKV-195 administered 5 days after virus inoculation showed marked protection against lethality in a stringent mouse model of infection.

Keywords: Zika virus; cryo-EM structure; membrane-fusion inhibition; monoclonal antibody; neutralization mechanism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Cryoelectron Microscopy / methods
  • Disease Models, Animal
  • Epitopes / immunology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Vaccination / methods
  • Viral Envelope Proteins / immunology
  • Zika Virus / immunology*
  • Zika Virus Infection / immunology*


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

Associated data

  • PDB/6MID