SARS-CoV-2 monoclonal antibody treatment followed by vaccination shifts human memory B cell epitope recognition suggesting antibody feedback
Year: 2023
Type: preprint
Abstract: ABSTRACT Therapeutic anti-SARS-CoV-2 monoclonal antibodies (mAbs) have been extensively studied in humans, but the impact on immune memory of mAb treatment during an ongoing immune response has remained unclear. Here, we evaluated the effect of infusion of the anti-SARS-CoV-2 spike receptor binding domain (RBD) mAb bamlanivimab on memory B cells (MBCs) in SARS-CoV-2–infected individuals. Bamlanivimab treatment skewed the repertoire of memory B cells targeting Spike towards non-RBD epitopes. Furthermore, the relative affinity of RBD memory B cells was weaker in mAb-treated individuals compared to placebo-treated individuals over time. Subsequently, after mRNA COVID-19 vaccination, memory B cell differences persisted and mapped to a specific defect in recognition of the class II RBD site, the same RBD epitope recognized by bamlanivimab. These findings indicate a substantial role of antibody feedback in regulating human memory B cell responses, both to infection and vaccination. These data indicate that mAb administration can promote alterations in the epitopes recognized by the B cell repertoire, and the single administration of mAb can continue to determine the fate of B cells in response to additional antigen exposures months later. SIGNIFICANCE STATEMENT Evaluating the therapeutic use of monoclonal antibodies during SARS-CoV-2 infection requires a comprehensive understanding of their impact on B cell responses at the cellular level and how these responses are shaped after vaccination. We report for the first time the effect of bamlanivimab on SARS-CoV-2 specific human memory B cells of COVID-19 infected humans receiving, or not, mRNA immunization.
Authors: Camila H. Coelho, Nathaniel Bloom, Sydney I. Ramirez, Urvi M. Parikh, Amy Heaps, Scott F. Sieg, Alex Greninger, Justin Ritz, Carlee Moser, Joseph J. Eron, Judith S. Currier, Paul Klekotka, David A. Wohl, Eric S. Daar, Jonathan Li, Michael D. Hughes, Kara W. Chew, Davey M. Smith, Shane Crotty, the Accelerating COVID-19 Therapeutic Interventions and Vaccines–2/A5401 (ACTIV-2/A5401) Study Team
Institutions: La Jolla Institute for Immunology, Icahn School of Medicine at Mount Sinai, University of California San Diego, University of Pittsburgh, Case Western Reserve University, University of Washington, Harvard University, University of North Carolina at Chapel Hill, University of California, Los Angeles, The Lundquist Institute, Harbor–UCLA Medical Center, Brigham and Women's Hospital
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Human immune memory to COVID-19, vaccines, and respiratory pathogens, Statistical and Data Management Center (SDMC), Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG), University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit, Combating Antibiotic Resistance Into the Next Generation (CARING)
OpenAlex ID: W4388923730