101. Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor
- Author
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Samantha M. Townsley, Kayvon Modjarrad, Bradley S. Hollidge, Rafael A. Larocca, Darci R. Smith, Merlin L. Robb, Rajeshwer S. Sankhala, Ariadna Grinyo i Escuer, Nicole A. Doria-Rose, Kareem Kabra, Wiriya Rutvisuttinunt, Aviva Geretz, David J. Leggat, James D. Brien, Justice Akuoku Frimpong, Gregory D. Gromowski, Misook Choe, Ursula Tran, Edgar Davidson, Irina Maljkovic Berry, Mayda Hernandez, Shelly J. Krebs, Adrian B. McDermott, Richard G. Jarman, Aubrey L. Bryan, M. Gordon Joyce, Weam I. Zaky, Kathryn E. Stephenson, Gina Donofrio, Peter Abbink, Rafael De La Barrera, Candace Hope Bias, Jinyan Liu, Vincent Dussupt, Nelson L. Michael, Sarah L. George, Morgane Rolland, Ningbo Jian, Dan H. Barouch, Benjamin J. Doranz, Hongjun Bai, Kenneth H. Eckels, Elizabeth Barranco, Amelia K. Pinto, Rasmi Thomas, Letzibeth Mendez-Rivera, Nubia Botero, Michael K. McCracken, Michael Koren, Tanya Cook, Ian Setliff, and Ivelin S. Georgiev
- Subjects
0301 basic medicine ,Letter ,viruses ,Dengue virus ,medicine.disease_cause ,Antibodies, Viral ,Dengue fever ,Zika virus ,Dengue ,Mice ,0302 clinical medicine ,Chlorocebus aethiops ,Vaccines ,Mice, Inbred BALB C ,biology ,Zika Virus Infection ,Vaccination ,virus diseases ,Antibodies, Monoclonal ,General Medicine ,Tissue Donors ,Flavivirus ,030220 oncology & carcinogenesis ,Infectious diseases ,Female ,Structural biology ,Protein Binding ,Viremia ,Cross Reactions ,Microbiology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Inhibitory Concentration 50 ,Protein Domains ,medicine ,Animals ,Humans ,Vero Cells ,business.industry ,Viral Vaccines ,Zika Virus ,biochemical phenomena, metabolism, and nutrition ,Dengue Virus ,medicine.disease ,biology.organism_classification ,Virology ,Antibodies, Neutralizing ,Mice, Inbred C57BL ,030104 developmental biology ,Immunization ,Vaccines, Inactivated ,Immunoglobulin G ,Inactivated vaccine ,business ,Epitope Mapping - 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., 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.
- Published
- 2020