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

Vincent Dussupt, Rajeshwer S. Sankhala, Gregory D. Gromowski, Gina Donofrio, Rafael A. De La Barrera, Rafael A. Larocca, Weam Zaky, Letzibeth Mendez-Rivera, Misook Choe, Edgar Davidson, Michael K. McCracken, James D. Brien, Peter Abbink, Hongjun Bai, Aubrey L. Bryan, Candace Hope Bias, Irina Maljkovic Berry, Nubia Botero, Tanya Cook, Nicole A. Doria-RoseAriadna Grinyo i. Escuer, Justice Akuoku Frimpong, Aviva Geretz, Mayda Hernandez, Bradley S. Hollidge, Ningbo Jian, Kareem Kabra, David J. Leggat, Jinyan Liu, Amelia K. Pinto, Wiriya Rutvisuttinunt, Ian Setliff, Ursula Tran, Samantha Townsley, Benjamin J. Doranz, Morgane Rolland, Adrian B. McDermott, Ivelin S. Georgiev, Rasmi Thomas, Merlin L. Robb, Kenneth H. Eckels, Elizabeth Barranco, Michael Koren, Darci R. Smith, Richard G. Jarman, Sarah L. George, Kathryn E. Stephenson, Dan H. Barouch, Kayvon Modjarrad, Nelson L. Michael, M. Gordon Joyce, Shelly J. Krebs

Research output: Contribution to journalLetterpeer-review

56 Scopus citations

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.

Original languageEnglish
Pages (from-to)228-235
Number of pages8
JournalNature Medicine
Volume26
Issue number2
DOIs
StatePublished - Feb 1 2020

Bibliographical note

Publisher Copyright:
© 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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