SARS-CoV-2 monoclonal antibody treatment followed by vaccination shifts human memory B cell epitope recognition suggesting antibody feedback

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 (R...

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Bibliographic Details
Published in:bioRxiv 2023-11
Main Authors: Coelho, Camila H, Bloom, Nathaniel, Ramirez, Sydney I, Parikh, Urvi M, Heaps, Amy, Sieg, Scott F, Greninger, Alex, Ritz, Justin, Moser, Carlee, Eron, Joseph J, Currier, Judith S, Klekotka, Paul, Wohl, David A, Daar, Eric S, Li, Jonathan, Hughes, Michael D, Chew, Kara W, Smith, Davey M, Crotty, Shane
Format: Article
Language:English
Subjects:
Antibodies
COVID-19
Epitopes
Equity stake
Feedback
Immunological memory
Immunology
Lymphocytes B
Memory cells
Monoclonal antibodies
mRNA
Severe acute respiratory syndrome coronavirus 2
Vaccination
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Summary: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.
ISSN:2692-8205
2692-8205
DOI:10.1101/2023.11.21.567575