A global collaboration for systematic analysis of broad-ranging antibodies against the SARS-CoV-2 spike protein

Sharon L Schendel; Xiaoying Yu; Peter J Halfmann; Jarjapu Mahita; Brendan Ha; Kathryn M Hastie; Haoyang Li; Daniel Bedinger; Camille Troup; Kan Li; Natalia Kuzmina; Jordi B Torrelles; Jennifer E Munt; Melissa Maddocks; Mary Osei-Twum; Heather M Callaway; CoVIC-DB Team; Stephen Reece; Anne Palser; Paul Kellam; S Moses Dennison; Richard H C Huntwork; Gillian Q Horn; Milite Abraha; Elizabeth Feeney; Luis Martinez-Sobrido; Paula A Pino; Amberlee Hicks; Chengjin Ye; Jun-Gyu Park; Billie Maingot; Sivakumar Periasamy; Michael Mallory; Trevor Scobey; Marie-Noelle Lepage; Natalie St-Amant; Sarwat Khan; Anaïs Gambiez; Coronavirus Immunotherapeutic Consortium; Ralph S Baric; Alexander Bukreyev; Luc Gagnon; Timothy Germann; Yoshihiro Kawaoka; Georgia D Tomaras; Bjoern Peters; Erica Ollmann Saphire

doi:10.1016/j.celrep.2025.115499

A global collaboration for systematic analysis of broad-ranging antibodies against the SARS-CoV-2 spike protein

Cell Rep. 2025 Apr 22;44(4):115499. doi: 10.1016/j.celrep.2025.115499. Epub 2025 Apr 2.

Authors

Sharon L Schendel¹, Xiaoying Yu¹, Peter J Halfmann², Jarjapu Mahita¹, Brendan Ha¹, Kathryn M Hastie¹, Haoyang Li¹, Daniel Bedinger³, Camille Troup³, Kan Li⁴, Natalia Kuzmina⁵, Jordi B Torrelles⁶, Jennifer E Munt⁷, Melissa Maddocks⁷, Mary Osei-Twum⁸, Heather M Callaway¹; CoVIC-DB Team¹; Stephen Reece⁹, Anne Palser¹⁰, Paul Kellam¹¹, S Moses Dennison⁴, Richard H C Huntwork⁴, Gillian Q Horn⁴, Milite Abraha⁴, Elizabeth Feeney⁴, Luis Martinez-Sobrido⁶, Paula A Pino¹², Amberlee Hicks¹², Chengjin Ye⁶, Jun-Gyu Park¹², Billie Maingot¹², Sivakumar Periasamy¹³, Michael Mallory⁷, Trevor Scobey⁷, Marie-Noelle Lepage⁸, Natalie St-Amant⁸, Sarwat Khan⁸, Anaïs Gambiez¹; Coronavirus Immunotherapeutic Consortium; Ralph S Baric¹⁴, Alexander Bukreyev¹⁵, Luc Gagnon⁸, Timothy Germann³, Yoshihiro Kawaoka¹⁶, Georgia D Tomaras⁴, Bjoern Peters¹⁷, Erica Ollmann Saphire¹⁸

Affiliations

¹ Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
² Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
³ Carterra, Inc., Salt Lake City, UT 84103, USA.
⁴ Center for Human Systems Immunology, Departments of Surgery and Integrative Immunobiology, Duke University, Durham, NC 27701, USA.
⁵ Department of Pathology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX 77555, USA; Galveston National Laboratory, 301 University Boulevard, Galveston, TX 77550, USA.
⁶ Disease Intervention and Prevention and Population Health Programs, Texas Biomedical Research Institute, San Antonio, TX 78227, USA; Population Health Program, International Center for the Advancement of Research & Education (I-CARE), Texas Biomedical Research Institute, San Antonio, TX 78227, USA.
⁷ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA.
⁸ Nexelis, a Q2 Solutions Company, 525 Boulevard Cartier Ouest, Laval, QC H7V 3S8, Canada.
⁹ Kymab, a Sanofi Company, Babraham Research Campus, Cambridge CB22 3AT, UK.
¹⁰ RQ Biotechnology Ltd., London W12 7RZ, UK.
¹¹ RQ Biotechnology Ltd., London W12 7RZ, UK; Department of Infectious Diseases, Faculty of Medicine, Imperial College, London SW7 2AZ, UK.
¹² Disease Intervention and Prevention and Population Health Programs, Texas Biomedical Research Institute, San Antonio, TX 78227, USA.
¹³ Galveston National Laboratory, 301 University Boulevard, Galveston, TX 77550, USA.
¹⁴ Population Health Program, International Center for the Advancement of Research & Education (I-CARE), Texas Biomedical Research Institute, San Antonio, TX 78227, USA; Department of Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹⁵ Department of Pathology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX 77555, USA; Galveston National Laboratory, 301 University Boulevard, Galveston, TX 77550, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
¹⁶ Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA; Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo 162-8655, Japan; Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), University of Tokyo, Tokyo 162-8655, Japan.
¹⁷ Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address: bpeters@lji.org.
¹⁸ Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address: erica@lji.org.

Abstract

The Coronavirus Immunotherapeutic Consortium (CoVIC) conducted side-by-side comparisons of over 400 anti-SARS-CoV-2 spike therapeutic antibody candidates contributed by large and small companies as well as academic groups on multiple continents. Nine reference labs analyzed antibody features, including in vivo protection in a mouse model of infection, spike protein affinity, high-resolution epitope binning, ACE-2 binding blockage, structures, and neutralization of pseudovirus and authentic virus infection, to build a publicly accessible dataset in the database CoVIC-DB. High-throughput, high-resolution binning of CoVIC antibodies defines a broad and predictive landscape of antibody epitopes on the SARS-CoV-2 spike protein and identifies features associated with durable potency against multiple SARS-CoV-2 variants of concern and high in vivo efficacy. Results of the CoVIC studies provide a guide for selecting effective and durable antibody therapeutics and for immunogen design as well as providing a framework for rapid response to future viral disease outbreaks.

Keywords: COVID-19; CP: Immunology; SARS-CoV-2 spike protein; coronavirus; high-resolution epitope binning; neutralization; therapeutic antibodies.

MeSH terms

Angiotensin-Converting Enzyme 2 / metabolism
Animals
Antibodies, Neutralizing / immunology
Antibodies, Viral* / immunology
Antibodies, Viral* / therapeutic use
COVID-19* / immunology
COVID-19* / virology
Epitopes / immunology
Humans
Mice
SARS-CoV-2* / immunology
Spike Glycoprotein, Coronavirus* / immunology

Substances

Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
Antibodies, Viral
Epitopes
Antibodies, Neutralizing
Angiotensin-Converting Enzyme 2