Publications
Cell reportsJun 2024 |
43
(
6
),
114307
DOI:
10.1016/j.celrep.2024.114307

Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple spike epitopes

Hurtado, Jonathan; Rogers, Thomas F; Jaffe, David B; Adams, Bruce A; Bangaru, Sandhya; Garcia, Elijah; Capozzola, Tazio; Messmer, Terrence; Sharma, Pragati; Song, Ge; Beutler, Nathan; He, Wanting; Dueker, Katharina; Musharrafieh, Rami; Burbach, Sarah; Truong, Alina; Stubbington, Michael J T; Burton, Dennis R; Andrabi, Raiees; Ward, Andrew B; McDonnell, Wyatt J; Briney, Bryan
Product Used
Genes
Abstract
The development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees to isolate over 9,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. Among the recovered antibodies was TXG-0078, an N-terminal domain (NTD)-specific neutralizing mAb that recognizes diverse alpha- and beta-coronaviruses. TXG-0078 achieves its exceptional binding breadth while utilizing the same VH1-24 variable gene signature and heavy-chain-dominant binding pattern seen in other NTD-supersite-specific neutralizing Abs with much narrower specificity. We also report CC24.2, a pan-sarbecovirus neutralizing antibody that targets a unique receptor-binding domain (RBD) epitope and shows similar neutralization potency against all tested SARS-CoV-2 variants, including BQ.1.1 and XBB.1.5. A cocktail of TXG-0078 and CC24.2 shows protection in vivo, suggesting their potential use in variant-resistant therapeutic Ab cocktails and as templates for pan-coronavirus vaccine design.
Product Used
Genes

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