Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones

Lima, Noemia S.; Mukhamedova, Maryam; Johnston, Timothy S.; Wagner, Danielle A.; Henry, Amy R.; Wang, Lingshu; Yang, Eun Sung; Zhang, Yi; Birungi, Kevina; Black, Walker P; O’Dell, Sijy; Schmidt, Stephen D.; Moon, Damee; Lorang, Cynthia G.; Zhao, Boyu; Chen, Man; Boswell, Kristin L.; Roberts-Torres, Jesmine; Davis, Rachel L.; Peyton, Lowrey; Narpala, Sandeep; O’Connell, Sarah; Wang, Jennifer; Schrager, Alexander M.; Talana, Chloe Adrienna; Leung, Kwanyee; Shi, Wei; Khashab, Rawan; Biber, Asaf; Zilberman, Tal; Rhein, Joshua; Vetter, Sara M.; Ahmed, Afeefa; Novik, Laura; Widge, Alicia T.; Gordon, Ingelise J.; Guech, Mercy; Teng, I-Ting; Phung, Emily; Ruckwardt, Tracy J.; Pegu, Amarendra; Doria‐Rose, Nicole A.; Gaudinski, Martin R.; Koup, Richard A.; Kwong, Peter D.; McDermott, Adrian B.; Amit, Sharon; Schacker, Timothy W.; Levy, Itzchak; Mascola, John R.; Sullivan, Nancy J.; Schramm, Chaim A.; Douek, Daniel C.

doi:10.1101/2022.03.28.486152

Cited by 2 publications

(1 citation statement)

References 131 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, we have provided WA-1, Beta, Delta, and Omicron probes for confirming elicitation of cross-reactive B cells by mRNA-1273 or mRNA-Omicron boost and for evaluating their ACE2 binding inhibition [ 44 ]. Another recent research identified convergent immune responses elicited by Beta- or Gamma-infection when compared to ancestral virus infection using S2P, RBD, and NTD probes from WA-1, Beta, and Gamma variants [ 45 ]. To facilitate usage of these probes in COVID-19 related research, the full matrix of probe regions and variants is being made available at Addgene for dissemination, including plasmids for the recently emerged Omicron sublineage BA.2 ( S1 and S2 Tables).…”

Section: Discussionmentioning

confidence: 99%

Molecular probes of spike ectodomain and its subdomains for SARS-CoV-2 variants, Alpha through Omicron

et al. 2022

View full text Add to dashboard Cite

Since the outbreak of the COVID-19 pandemic, widespread infections have allowed SARS-CoV-2 to evolve in human, leading to the emergence of multiple circulating variants. Some of these variants show increased resistance to vaccine-elicited immunity, convalescent plasma, or monoclonal antibodies. In particular, mutations in the SARS-CoV-2 spike have drawn attention. To facilitate the isolation of neutralizing antibodies and the monitoring of vaccine effectiveness against these variants, we designed and produced biotin-labeled molecular probes of variant SARS-CoV-2 spikes and their subdomains, using a structure-based construct design that incorporated an N-terminal purification tag, a specific amino acid sequence for protease cleavage, the variant spike-based region of interest, and a C-terminal sequence targeted by biotin ligase. These probes could be produced by a single step using in-process biotinylation and purification. We characterized the physical properties and antigenicity of these probes, comprising the N-terminal domain (NTD), the receptor-binding domain (RBD), the RBD and subdomain 1 (RBD-SD1), and the prefusion-stabilized spike ectodomain (S2P) with sequences from SARS-CoV-2 variants of concern or of interest, including variants Alpha, Beta, Gamma, Epsilon, Iota, Kappa, Delta, Lambda, Mu, and Omicron. We functionally validated probes by using yeast expressing a panel of nine SARS-CoV-2 spike-binding antibodies and confirmed sorting capabilities of variant probes using yeast displaying libraries of plasma antibodies from COVID-19 convalescent donors. We deposited these constructs to Addgene to enable their dissemination. Overall, this study describes a matrix of SARS-CoV-2 variant molecular probes that allow for assessment of immune responses, identification of serum antibody specificity, and isolation and characterization of neutralizing antibodies.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular probes of spike ectodomain and its subdomains for SARS-CoV-2 variants, Alpha through Omicron

et al. 2022

View full text Add to dashboard Cite

show abstract

Contrasting Effects of SARS-CoV-2 Vaccination vs. Infection on Antibody and TCR Repertoires

Braun,

Hill,

Contreras

et al. 2023

Preprint

View full text Add to dashboard Cite

Antibodies and helper T cells play important roles in SARS-CoV-2 infection and vaccination. We sequenced B– and T-cell receptor repertoires (BCR/TCR) from the blood of 251 infectees, vaccinees, and controls to investigate whether features of these repertoires could predict subjects’ SARS-CoV-2 neutralizing antibody titer (NAbs), as measured by enzyme-linked immunosorbent assay (ELISA). We sequenced recombined immunoglobulin heavy-chain (IGH), TCRβ (TRB), and TCRδ (TRD) genes in parallel from all subjects, including select B– and T-cell subsets in most cases, with a focus on their hypervariable CDR3 regions, and correlated this AIRRseq data with demographics and clinical findings from subjects’ electronic health records. We found that age affected NAb levels in vaccinees but not infectees. Intriguingly, we found that vaccination, but not infection, has a substantial effect on non-productively recombined IGHs, suggesting a vaccine effect that precedes clonal selection. We found that repertoires’ binding capacity to known SARS-CoV-2-specific CD4+ TRBs performs as well as the best hand-tuned fuzzy matching at predicting a protective level of NAbs, while also being more robust to repertoire sample size and not requiring hand-tuning. The overall conclusion from this large, unbiased, clinically well annotated dataset is that B– and T-cell adaptive responses to SARS-CoV-2 infection and vaccination are surprising, subtle, and diffuse. We discuss methodological and statistical challenges faced in attempting to define and quantify such strong-but-diffuse repertoire signatures and present tools and strategies for addressing these challenges.

show abstract

Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones

Cited by 2 publications

References 131 publications

Molecular probes of spike ectodomain and its subdomains for SARS-CoV-2 variants, Alpha through Omicron

Molecular probes of spike ectodomain and its subdomains for SARS-CoV-2 variants, Alpha through Omicron

Contrasting Effects of SARS-CoV-2 Vaccination vs. Infection on Antibody and TCR Repertoires

Contact Info

Product

Resources

About