Pre-existing SARS-CoV-2 immunity influences potency, breadth, and durability of the humoral response to SARS-CoV-2 vaccination

• Type of Material: Article
• Authors: Grace Mantus, Children's Healthcare of Atlanta; Lindsay E Nyhoff, Children's Healthcare of Atlanta; Venkata-Viswanadh Edara, Children's Healthcare of Atlanta; Veronika Zarnitsyna, Emory University; Caroline R Ciric, Children's Healthcare of Atlanta; Maria W Flowers, Children's Healthcare of Atlanta; Carson Norwood, Children's Healthcare of Atlanta; Madison Ellis, Emory University School of Medicine; Laila Hussaini, Children's Healthcare of Atlanta; Kelly E Manning, Emory University School of Medicine; Kathy Stephens, Children's Healthcare of Atlanta; Evan Anderson, Emory University; Rafi Ahmed, Emory University; Mehul Suthar, Emory University; Jens Wrammert, Emory University
• Language: English
• Date: 2022-04-19
• Publisher: Elsevier Inc
• Publication Version: Final Published Version
• Copyright Statement: © 2022 The Author(s)
• Final Published Version (URL): http://dx.doi.org/10.1016/j.xcrm.2022.100603
• Title of Journal or Parent Work: Cell Reports Medicine
• Volume: 3
• Issue: 4
• Start Page: 100603
• End Page: 100603
• Grant/Funding Information: The research reported in this publication was supported in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under award numbers 3U19AI057266-17S1, 3U19AI057266-17S2, 1U54CA260563, and T32AI074492 and under HHSN272201400004C and 75N93021C00017 (NIAID Centers of Excellence for Influenza Research and Surveillance, CEIRS) and NIH P51 OD011132 to Emory University. This work was also supported in part by the Emory Executive Vice President for Health Affairs Synergy Fund award, 75D30121C10084, COVID-Catalyst-I3 Funds from the Woodruff Health Sciences Center and Emory School of Medicine, the Pediatric Research Alliance Center for Childhood Infections and Vaccines and Children’s Healthcare of Atlanta, The Oliver S. and Jennie R. Donaldson Charitable Trust, the Vital Project/Proteus Fund, and Woodruff Health Sciences Center 2020 COVID-19 CURE Award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: humoral response; COVID-19 Vaccines; mRNA vaccination; SARS-CoV-2; Humans; memory B cells; Viral Vaccines; COVID-19; Antibodies, Viral; Vaccination; RBD; antibody durability
• Research Categories: Health Sciences, Immunology; Biology, Microbiology; Health Sciences, Medicine and Surgery

Abstract

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic highlights the importance of determining the breadth and durability of humoral immunity to SARS-CoV-2 mRNA vaccination. Herein, we characterize the humoral response in 27 naive and 40 recovered vaccinees. SARS-CoV-2-specific antibody and memory B cell (MBC) responses are durable up to 6 months, although antibody half-lives are shorter for naive recipients. The magnitude of the humoral responses to vaccination strongly correlates with responses to initial SARS-CoV-2 infection. Neutralization titers are lower against SARS-CoV-2 variants in both recovered and naive vaccinees, with titers more reduced in naive recipients. While the receptor-binding domain (RBD) is the main neutralizing target of circulating antibodies, Moderna-vaccinated naives show a lesser reliance on RBDs, with >25% neutralization remaining after depletion of RBD-binding antibodies. Overall, we observe that vaccination induces higher peak titers and improves durability in recovered compared with naive vaccinees. These findings have broad implications for current vaccine strategies deployed against the SARS-CoV-2 pandemic.