Cell Reports (Jun 2024)
Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple spike epitopes
- Jonathan Hurtado,
- Thomas F. Rogers,
- David B. Jaffe,
- Bruce A. Adams,
- Sandhya Bangaru,
- Elijah Garcia,
- Tazio Capozzola,
- Terrence Messmer,
- Pragati Sharma,
- Ge Song,
- Nathan Beutler,
- Wanting He,
- Katharina Dueker,
- Rami Musharrafieh,
- Sarah Burbach,
- Alina Truong,
- Michael J.T. Stubbington,
- Dennis R. Burton,
- Raiees Andrabi,
- Andrew B. Ward,
- Wyatt J. McDonnell,
- Bryan Briney
Affiliations
- Jonathan Hurtado
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA
- Thomas F. Rogers
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA
- David B. Jaffe
- 10x Genomics, Inc., 6230 Stoneridge Mall Road, Pleasanton, CA 94588, USA
- Bruce A. Adams
- 10x Genomics, Inc., 6230 Stoneridge Mall Road, Pleasanton, CA 94588, USA
- Sandhya Bangaru
- Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA 92037, USA
- Elijah Garcia
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Tazio Capozzola
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA
- Terrence Messmer
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA
- Pragati Sharma
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA
- Ge Song
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA
- Nathan Beutler
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Wanting He
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA
- Katharina Dueker
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA
- Rami Musharrafieh
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA
- Sarah Burbach
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA
- Alina Truong
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA
- Michael J.T. Stubbington
- 10x Genomics, Inc., 6230 Stoneridge Mall Road, Pleasanton, CA 94588, USA
- Dennis R. Burton
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of MGH, Harvard and MIT, Cambridge, MA 02139, USA
- Raiees Andrabi
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA
- Andrew B. Ward
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
- Wyatt J. McDonnell
- 10x Genomics, Inc., 6230 Stoneridge Mall Road, Pleasanton, CA 94588, USA; Corresponding author
- Bryan Briney
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Center for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Multi-Omics Vaccine Evaluation Consortium, The Scripps Research Institute, La Jolla, CA 92037, USA; Corresponding author
- Journal volume & issue
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Vol. 43,
no. 6
p. 114307
Abstract
Summary: 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.
