Asymptomatic or symptomatic SARS-CoV-2 infection plus vaccination confers increased adaptive immunity to variants of concern

Sun, Peifang; Ramos, Irene; Coelho, Camila H.; Grifoni, Alba; Balinsky, Corey A.; Vangeti, Sindhu; Tarke, Alison; Bloom, Nathaniel I.; Jani, Vihasi; Jakubski, Silvia J.; Boulifard, David A.; Cooper, Elizabeth; Goforth, Carl; Marayag, Jan; Marrone, Amethyst; Nunez, Edgar; White, Lindsey; Porter, Chad K.; Sugiharto, Victor A.; Schilling, Megan A.; Mahajan, Avinash S.; Beckett, Charmagne; Sette, Alessandro; Sealfon, Stuart C.; Crotty, Shane; Letizia, Andrew G.

doi:10.1016/j.isci.2022.105202

Cited by 4 publications

(1 citation statement)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The two study designs differ, but we observed multiple similarities in the immunological outcomes found between the two after mAb infusions: a) IgM+ MBCs were increased; b) RBD MBC affinities were reduced; and c) frequencies of MBCs specific for an RBD epitope recognized by the therapeutic mAb were reduced. Variant recognition can increase in response to vaccination (34, 35). Following vaccination, the frequency of MBCs that cross-reacted with BA.1 and BA.5 RBD was increased in the mAb treated group compared to the placebo group.…”

Section: Discussionmentioning

confidence: 99%

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

Coelho,

Bloom,

Ramirez

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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 STATEMENTEvaluating 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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Coelho,

Bloom,

Ramirez

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

The MegaPool Approach to Characterize Adaptive CD4+ and CD8+ T Cell Responses

da Silva Antunes,

Weiskopf,

Sidney

et al. 2023

Current Protocols

Self Cite

View full text Add to dashboard Cite

Epitopes recognized by T cells are a collection of short peptide fragments derived from specific antigens or proteins. Immunological research to study T cell responses is hindered by the extreme degree of heterogeneity of epitope targets, which are usually derived from multiple antigens; within a given antigen, hundreds of different T cell epitopes can be recognized, differing from one individual to the next because T cell epitope recognition is restricted by the epitopes’ ability to bind to MHC molecules, which are extremely polymorphic in different individuals. Testing large pools encompassing hundreds of peptides is technically challenging because of logistical considerations regarding solvent‐induced toxicity. To address this issue, we developed the MegaPool (MP) approach based on sequential lyophilization of large numbers of peptides that can be used in a variety of assays to measure T cell responses, including ELISPOT, intracellular cytokine staining, and activation‐induced marker assays, and that has been validated in the study of infectious diseases, allergies, and autoimmunity. Here, we describe the procedures for generating and testing MPs, starting with peptide synthesis and lyophilization, as well as a step‐by‐step guide and recommendations for their handling and experimental usage. Overall, the MP approach is a powerful strategy for studying T cell responses and understanding the immune system's role in health and disease. © 2023 Wiley Periodicals LLC.Basic Protocol 1: Generation of peptide pools (“MegaPools”)Basic Protocol 2: MegaPool testing and quantitation of antigen‐specific T cell responses

show abstract

SARS-CoV-2 Monoclonal Antibody Treatment Followed by Vaccination Shifts Human Memory B-Cell Epitope Recognition, Suggesting Antibody Feedback

Bloom,

Ramirez,

Cohn

et al. 2024

The Journal of Infectious Diseases

View full text Add to dashboard Cite

Therapeutic monoclonal antibodies (mAbs) have been studied in humans, but the impact on immune memory of mAb treatment during an ongoing infection has remained unclear. 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 reduction 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 memory B cell responses to infection, and single mAb administration can continue to impact memory B cell responses to additional antigen exposures months later.

show abstract

Asymptomatic or symptomatic SARS-CoV-2 infection plus vaccination confers increased adaptive immunity to variants of concern

Cited by 4 publications

References 53 publications

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

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

The MegaPool Approach to Characterize Adaptive CD4+ and CD8+ T Cell Responses

SARS-CoV-2 Monoclonal Antibody Treatment Followed by Vaccination Shifts Human Memory B-Cell Epitope Recognition, Suggesting Antibody Feedback

Contact Info

Product

Resources

About