Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor

Nat Med. 2020 Feb;26(2):228-235. doi: 10.1038/s41591-019-0746-2. Epub 2020 Feb 3.

Abstract

Zika virus (ZIKV) has caused significant disease, with widespread cases of neurological pathology and congenital neurologic defects. Rapid vaccine development has led to a number of candidates capable of eliciting potent ZIKV-neutralizing antibodies (reviewed in refs. 1-3). Despite advances in vaccine development, it remains unclear how ZIKV vaccination affects immune responses in humans with prior flavivirus immunity. Here we show that a single-dose immunization of ZIKV purified inactivated vaccine (ZPIV)4-7 in a dengue virus (DENV)-experienced human elicited potent cross-neutralizing antibodies to both ZIKV and DENV. Using a unique ZIKV virion-based sorting strategy, we isolated and characterized multiple antibodies, including one termed MZ4, which targets a novel site of vulnerability centered on the Envelope (E) domain I/III linker region and protects mice from viremia and viral dissemination following ZIKV or DENV-2 challenge. These data demonstrate that Zika vaccination in a DENV-experienced individual can boost pre-existing flavivirus immunity and elicit protective responses against both ZIKV and DENV. ZPIV vaccination in Puerto Rican individuals with prior flavivirus experience yielded similar cross-neutralizing potency after a single vaccination, highlighting the potential benefit of ZIKV vaccination in flavivirus-endemic areas.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Chlorocebus aethiops
  • Cross Reactions
  • Dengue / immunology*
  • Dengue Virus
  • Epitope Mapping
  • Female
  • Flavivirus / metabolism
  • Humans
  • Immunoglobulin G / chemistry
  • Inhibitory Concentration 50
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Protein Binding
  • Protein Domains
  • Tissue Donors*
  • Vaccination
  • Vaccines, Inactivated / therapeutic use
  • Vero Cells
  • Viral Vaccines / therapeutic use*
  • Viremia
  • Zika Virus
  • Zika Virus Infection / immunology*
  • Zika Virus Infection / prevention & control*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G
  • Vaccines, Inactivated
  • Viral Vaccines