Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients

• Type of Material: Article
• Authors: Mehul Suthar, Emory University; Matthew G. Zimmerman, Emory University; Robert C. Kauffman, Emory University; Grace Mantus, Emory University; Susanne L. Linderman, Emory University; William Hudson, Emory University; Abigail Vanderheiden, Emory University; Lindsay Nyhoff, Emory University; Carl Davis, Emory University; Oluwaseyi Adekunle, Emory University; Maurizio Affer, Emory University; Melanie Sherman, Emory University; Stacian Reynolds, Emory University; Hans P. Verkerke, Emory University; David N. Alter, Emory University; Jeannette Guarner, Emory University; Janetta Bryksin, Emory University; Michael C. Horwath, Emory University; Connie Arthur, Emory University; Natia Saakadze, Emory University; Geoffrey Smith, Emory University; Srilatha Edupuganti, Emory University; Erin Scherer, Emory University; Kieffer Hellmeister, Emory University; Andrew Cheng, Emory University; Juliet A. Morales, Emory University; Andrew Neish, Emory University; Sean Stowell, Emory University; Filipp Frank, Emory University; Eric Ortlund, Emory University; Evan Anderson, Emory University; Vineet D. Menachery, University of Texas Galveston; Nadine Rouphael, Emory University; Aneesh Mehta, Emory University; David Stephens, Emory University; Rafi Ahmed, Emory University; John Roback, Emory University; Jens Wrammert, Emory University
• Language: English
• Date: 2020-06-08
• Publisher: CellPress
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Author(s)
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.xcrm.2020.100040
• Title of Journal or Parent Work: Cell Reports Medicine
• Volume: 1
• Issue: 3
• Grant/Funding Information: This work was funded in part by an Emory EVPHA Synergy Fund award (M.S.S. and J.W.), and by the National Institutes of Health NIAID Infectious Diseases Clinical Research Consortium (IDCRC) UM1 AI148684 (D.S.S., R.A., and J.W), R01 AI137127 (J.W.), ORIP/OD P51OD011132 (M.S.S.), 5T32 AI074492 (S.L.L.), R00 AG049092 (V.D.M.), World Reference Center for Emerging Viruses and Arboviruses R24 AI120942 (V.D.M.), HIPC 5U19AI090023-10 (N.R., E.A., and A.M.), VTEU 1UM1AI148576-01 (E.A. and N.R.), and a grant from The Marcus Foundation (J.D.R). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: neutralizing antibody; spike protein; COVID-19; receptor-binding protein; coronavirus; SARS-CoV-2; serology test; protective immunity; humoral immune response
• Research Categories: Health Sciences, Immunology; Health Sciences, Pathology; Biology, Cell; Biology, Virology

Abstract

SARS-CoV-2, the virus responsible for COVID-19, is causing a devastating worldwide pandemic, and there is a pressing need to understand the development, specificity, and neutralizing potency of humoral immune responses during acute infection. We report a cross-sectional study of antibody responses to the receptor-binding domain (RBD) of the spike protein and virus neutralization activity in a cohort of 44 hospitalized COVID-19 patients. RBD-specific IgG responses are detectable in all patients 6 days after PCR confirmation. Isotype switching to IgG occurs rapidly, primarily to IgG1 and IgG3. Using a clinical SARS-CoV-2 isolate, neutralizing antibody titers are detectable in all patients by 6 days after PCR confirmation and correlate with RBD-specific binding IgG titers. The RBD-specific binding data were further validated in a clinical setting with 231 PCR-confirmed COVID-19 patient samples. These findings have implications for understanding protective immunity against SARS-CoV-2, therapeutic use of immune plasma, and development of much-needed vaccines.