Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes

Sankhala, Rajeshwer S.; Dussupt, Vincent; Donofrio, Gina; Gromowski, Gregory D.; De La Barrera, Rafael A.; Larocca, Rafael A.; Mendez-Rivera, Letzibeth; Lee, Anna; Choe, Misook; Zaky, Weam; Mantus, Grace; Jensen, Jaime L.; Chen, Wei-Hung; Gohain, Neelakshi; Bai, Hongjun; McCracken, Michael K.; Mason, Rosemarie D.; Leggat, David; Slike, Bonnie M.; Tran, Ursula; Jian, Ningbo; Abbink, Peter; Peterson, Rebecca; Mendes, Erica Araujo; Freitas de Oliveira Franca, Rafael; Calvet, Guilherme Amaral; Bispo de Filippis, Ana Maria; McDermott, Adrian; Roederer, Mario; Hernandez, Mayda; Albertus, Amie; Davidson, Edgar; Doranz, Benjamin J.; Rolland, Morgane; Robb, Merlin L.; Lynch, Rebecca M.; Barouch, Dan H.; Jarman, Richard G.; Thomas, Stephen J.; Modjarrad, Kayvon; Michael, Nelson L.; Krebs, Shelly J.; Joyce, M. Gordon

doi:10.1016/j.celrep.2023.112942

Title: Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes

Journal Article · 09 August 2023 · Cell Reports

DOI: https://doi.org/10.1016/j.celrep.2023.112942 · OSTI ID:2470065

Sankhala, Rajeshwer S. ^[1]; Dussupt, Vincent; Donofrio, Gina; Gromowski, Gregory D.; De La Barrera, Rafael A.; Larocca, Rafael A.; Mendez-Rivera, Letzibeth; Lee, Anna; Choe, Misook; Zaky, Weam; Mantus, Grace; Jensen, Jaime L.; Chen, Wei-Hung; Gohain, Neelakshi; Bai, Hongjun; McCracken, Michael K.; Mason, Rosemarie D.; Leggat, David; Slike, Bonnie M.; Tran, Ursula more »

Walter Reed Army Institute of Research, Silver Spring, MD (United States); Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD (United States); et al.

Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS); Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-06CH11357; SC0012704

OSTI ID:: 2470065

Journal Information:: Cell Reports, Journal Name: Cell Reports Journal Issue: 8 Vol. 42; ISSN 2211-1247

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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Title: Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes

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