Two immunogenic recombinant protein vaccine candidates showed disparate protective efficacy against Zika virus infection in rhesus macaques

Vaccine. 2021 Feb 5;39(6):915-925. doi: 10.1016/j.vaccine.2020.12.077. Epub 2021 Jan 13.

Abstract

Zika virus (ZIKV) infection has caused major public health problems recently. To develop subunit vaccines for ZIKV, we have previously constructed recombinant ZIKV envelope protein domain III (EDIII), and the entire ectodomain (E80, which comprises EDI, EDII and EDIII), as vaccine candidates and showed both of them being immunogenic and protective in murine models. In this follow-up study, we compared these vaccine candidates in non-human primates. Both of them elicited neutralizing antibody responses, but only E80 immunization inhibited ZIKV infection in both peripheral blood and monkey tissues, whereas EDIII increased blood ZIKV RNA through possibly antibody-dependent enhancement. Further investigations revealed that the virion-binding antibody response in E80 immunized monkeys persisted longer and stronger than in EDIII immunized monkeys. These results demonstrate that E80 is superior to EDIII as a vaccine candidate, and that the magnitude, quality and durability of virion-binding neutralizing antibodies are correlates of protection.

Keywords: Antibody-dependent enhancement; E80; EDIII; Non-human primate; Vaccine; Zika virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antibody Formation
  • Follow-Up Studies
  • Macaca mulatta
  • Recombinant Proteins / immunology
  • Viral Envelope Proteins / genetics
  • Viral Vaccines / immunology*
  • Zika Virus
  • Zika Virus Infection* / prevention & control

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Recombinant Proteins
  • Viral Envelope Proteins
  • Viral Vaccines