Journal
NATURE MEDICINE
Volume 26, Issue 2, Pages 228-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41591-019-0746-2
Keywords
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Funding
- US Department of the Army
- Defense Health Agency [0130602D16]
- US Department of Defense, Defense Health Agency [0130602D16]
- Henry M. Jackson Foundation
- Harvard Catalyst, Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health) [UL1 TR001102]
- Harvard University
- Vaccine Treatment Evaluation Unit (VTEU) at Saint Louis University [HHSN2722013000021I]
- National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Henry M. Jackson Foundation [W81XWH-07-2-0067]
- National Institute of General Medical Sciences from the National Institutes of Health at the Advanced Photon Source, Argonne National Laboratory [P41 GM103403]
- UChicago Argonne for the US Department of Energy, Office of Biological and Environmental Research [DE-AC02-06CH11357]
- DOE Office of Science by Brookhaven National Laboratory [DE-SC0012704]
- NIH [HHSN272201400058C]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI005143] Funding Source: NIH RePORTER
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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. Zika virus vaccination elicits Zika and dengue virus cross-neutralizing antibodies in flavivirus-exposed individuals, potentially enhancing the protective efficacy of the vaccine in flavivirus-endemic regions.
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