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 language | English |
|---|---|
| Pages (from-to) | 228-235 |
| Number of pages | 8 |
| Journal | Nature Medicine |
| Volume | 26 |
| Issue number | 2 |
| DOIs | |
| State | Published - 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.
Funding
We sincerely thank the clinical trial participants and staff. In addition, we thank M. Creegan, M. Eller and the MHRP FlowCore facility for help with FACS sorting and C. Kuklis, Q. Chen, D. Barvir, A. Srikanth, T. Li, C. Fung, B. Yadav, B. Sumlin, G. Ballarini, N. Burrell, R. Olson and A. Dean for technical support. X-ray diffraction data were collected at beamlines at the Advanced Photon Source, Argonne National Laboratory, and the National Synchrotron Light Source II. This work was primarily funded by the US Department of the Army and the Defense Health Agency (0130602D16) to K.M. Work at BIDMC under D.B. was performed with support from the US Department of Defense, Defense Health Agency (0130602D16), the Henry M. Jackson Foundation and the 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 Award UL1 TR001102) and with financial contributions from Harvard University and its affiliated academic healthcare centers. The ZPIV vaccine trial in Puerto Rico was funded by the Vaccine Treatment Evaluation Unit (VTEU) at Saint Louis University (contract no. HHSN2722013000021I) under S.L.G. The network of VTEUs is supported by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The funders of the clinical trials were involved in the clinical study design, clinical study operations and approval of the clinical protocols. The ZPIV program leads (K.M. and N.L.M.) and the study sponsors had final responsibility for the decision to submit for publication. This work was supported by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the US Department of Defense (DoD) under the leadership of N.L.M. and M.R. The Structural Biology Center (SBC) and Northeastern Collaborative Access Team (NE-CAT) beamlines are funded by the National Institute of General Medical Sciences from the National Institutes of Health (P41 GM103403) at the Advanced Photon Source, Argonne National Laboratory. SBC-CAT is operated by UChicago Argonne for the US Department of Energy, Office of Biological and Environmental Research under contract no. DE-AC02-06CH11357. This research used ID-17-1 (AMX) beamline of the National Synchrotron Light Source II, a US Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Brookhaven National Laboratory under contract no. DE-SC0012704. In addition, this work was supported by NIH contract no. HHSN272201400058C to B.J.D. Material has been reviewed by the Walter Reed Army Institute of Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers or the National Institutes of Health. The opinions or assertions contained herein are the private views of the authors, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70–25.
| Funders | Funder number |
|---|---|
| Advanced Photon Source | |
| US Department of the Army | |
| Vaccine Treatment Evaluation Unit | |
| National Institutes of Health (NIH) | UL1 TR001102 |
| U.S. Department of Defense | |
| U.S. Department of Energy EPSCoR | |
| National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences | P41 GM103403 |
| National Institute of Allergy and Infectious Diseases | UM1AI108568, W81XWH-07-2-0067, HHSN272201400058C |
| National Center for Research Resources | |
| Henry M. Jackson Foundation | |
| National Center for Advancing Translational Sciences (NCATS) | |
| Office of Science Programs | |
| Biological and Environmental Research | DE-AC02-06CH11357 |
| Argonne National Laboratory | |
| Brookhaven National Laboratory (BNL) | DE-SC0012704 |
| Division of Intramural Research, National Institute of Allergy and Infectious Diseases | |
| Harvard Transdisciplinary Research in Energetics and Cancer Center, Harvard University | |
| Harvard Catalyst | |
| Defense Health Agency | 0130602D16 |
| Walter Reed Army Institute of Research | |
| Saint Louis University |
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
