Immunogenicity and efficacy of zika virus envelope domain III in DNA, protein, and ChAdOx1 adenoviral-vectored vaccines

César López-Camacho, Giuditta De Lorenzo, Jose Luis Slon-Campos, Stuart Dowall, Peter Abbink, Rafael A. Larocca, Young Chan Kim, Monica Poggianella, Victoria Graham, Stephen Findlay-Wilson, Emma Rayner, Jennifer Carmichael, Wanwisa Dejnirattisai, Michael Boyd, Roger Hewson, Juthathip Mongkolsapaya, Gavin R. Screaton, Dan H. Barouch, Oscar R. Burrone, Arvind H. PatelArturo Reyes-Sandoval*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

The flavivirus envelope protein domain III (EDIII) was an effective immunogen against dengue virus (DENV) and other related flaviviruses. Whether this can be applied to the Zika virus (ZIKV) vaccinology remains an open question. Here, we tested the efficacy of ZIKV-EDIII against ZIKV infection, using several vaccine platforms that present the antigen in various ways. We provide data demonstrating that mice vaccinated with a ZIKV-EDIII as DNA or protein-based vaccines failed to raise fully neutralizing antibodies and did not control viremia, following a ZIKV challenge, despite eliciting robust antibody responses. Furthermore, we showed that ZIKV-EDIII encoded in replication-deficient Chimpanzee adenovirus (ChAdOx1-EDIII) elicited anti-ZIKV envelope antibodies in vaccinated mice but also provided limited protection against ZIKV in two physiologically different mouse challenge models. Taken together, our data indicate that contrary to what was shown for other flaviviruses like the dengue virus, which has close similarities with ZIKV-EDIII, this antigen might not be a suitable vaccine candidate for the correct induction of protective immune responses against ZIKV.

Original languageEnglish
Article number307
Pages (from-to)1-20
Number of pages20
JournalVaccines
Volume8
Issue number2
DOIs
Publication statusPublished - Jun 2020

Bibliographical note

Funding Information:
This report is independent research funded by the UK Department of Health and Social Care through Innovate UK ?New vaccines for global epidemics: development and manufacture? grant No. 972216 (ARS), and also funded from an ODA budget (Global Health (ODA), 16/107/05-Design, development and GMP manufacture of a Zika vaccine) (AHP, ARS). The views expressed in this publication are those of the authors and not necessarily those of the Department of Health and Social Care. ARS is a Jenner Investigator and an Oxford Martin Fellow. AP is supported by the UK Medical Research Council. JM is supported by an MRC-Newton Fund grant, GRS is a Wellcome Trust Senior Investigator. We would like to thank the Jenner Institute?s Vector Core Facility for producing and supplying the recombinant viral vectors. We also thank James Brewer and Hannah Scales for provision of ALUM-MPA adjuvant.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Adenovirus
  • DENV
  • EDIII
  • Vaccine
  • ZIKV

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