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Molecular basis for antiviral activity of two pediatric neutralizing antibodies targeting SARS-CoV-2 Spike RBD.
Chen, Yaozong; Prévost, Jérémie; Ullah, Irfan; Romero, Hugo; Lisi, Veronique; Tolbert, William D; Grover, Jonathan R; Ding, Shilei; Gong, Shang Yu; Beaudoin-Bussières, Guillaume; Gasser, Romain; Benlarbi, Mehdi; Vézina, Dani; Anand, Sai Priya; Chatterjee, Debashree; Goyette, Guillaume; Grunst, Michael W; Yang, Ziwei; Bo, Yuxia; Zhou, Fei; Béland, Kathie; Bai, Xiaoyun; Zeher, Allison R; Huang, Rick K; Nguyen, Dung N; Sherburn, Rebekah; Wu, Di; Piszczek, Grzegorz; Paré, Bastien; Matthies, Doreen; Xia, Di; Richard, Jonathan; Kumar, Priti; Mothes, Walther; Côté, Marceline; Uchil, Pradeep D; Lavallée, Vincent-Philippe; Smith, Martin A; Pazgier, Marzena; Haddad, Elie; Finzi, Andrés.
  • Chen Y; Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.
  • Prévost J; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
  • Ullah I; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
  • Romero H; Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Lisi V; Centre de Recherche du CHU Ste-Justine, Montreal, QC H3T 1C5, Canada.
  • Tolbert WD; Centre de Recherche du CHU Ste-Justine, Montreal, QC H3T 1C5, Canada.
  • Grover JR; Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.
  • Ding S; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Gong SY; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
  • Beaudoin-Bussières G; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
  • Gasser R; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.
  • Benlarbi M; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
  • Vézina D; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
  • Anand SP; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
  • Chatterjee D; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
  • Goyette G; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
  • Grunst MW; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
  • Yang Z; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
  • Bo Y; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.
  • Zhou F; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
  • Béland K; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
  • Bai X; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Zeher AR; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Huang RK; Department of Biochemistry, Microbiology and Immunology, Center for Infection, Immunity, and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
  • Nguyen DN; Unit on Structural Biology, Division of Basic and Translational Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
  • Sherburn R; Centre de Recherche du CHU Ste-Justine, Montreal, QC H3T 1C5, Canada.
  • Wu D; Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Piszczek G; Unit on Structural Biology, Division of Basic and Translational Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
  • Paré B; Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Matthies D; Unit on Structural Biology, Division of Basic and Translational Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
  • Xia D; Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Richard J; Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.
  • Kumar P; Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.
  • Mothes W; Biophysics Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Côté M; Biophysics Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Uchil PD; Département de Biochimie et Médecine Moléculaire, Université de Montréal, Montreal, QC H3T 1J4, Canada.
  • Lavallée VP; Unit on Structural Biology, Division of Basic and Translational Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
  • Smith MA; Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Pazgier M; Centre de Recherche du CHUM (CRCHUM), Montreal, QC H2X 0A9, Canada.
  • Haddad E; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.
  • Finzi A; Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
iScience ; 26(1): 105783, 2023 Jan 20.
Article in English | MEDLINE | ID: covidwho-2149918
ABSTRACT
Neutralizing antibodies (NAbs) hold great promise for clinical interventions against SARS-CoV-2 variants of concern (VOCs). Understanding NAb epitope-dependent antiviral mechanisms is crucial for developing vaccines and therapeutics against VOCs. Here we characterized two potent NAbs, EH3 and EH8, isolated from an unvaccinated pediatric patient with exceptional plasma neutralization activity. EH3 and EH8 cross-neutralize the early VOCs and mediate strong Fc-dependent effector activity in vitro. Structural analyses of EH3 and EH8 in complex with the receptor-binding domain (RBD) revealed the molecular determinants of the epitope-driven protection and VOC evasion. While EH3 represents the prevalent IGHV3-53 NAb whose epitope substantially overlaps with the ACE2 binding site, EH8 recognizes a narrow epitope exposed in both RBD-up and RBD-down conformations. When tested in vivo, a single-dose prophylactic administration of EH3 fully protected stringent K18-hACE2 mice from lethal challenge with Delta VOC. Our study demonstrates that protective NAbs responses converge in pediatric and adult SARS-CoV-2 patients.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Language: English Journal: IScience Year: 2023 Document Type: Article Affiliation country: J.isci.2022.105783

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study / Randomized controlled trials Topics: Vaccines / Variants Language: English Journal: IScience Year: 2023 Document Type: Article Affiliation country: J.isci.2022.105783