Broad SARS-CoV-2 neutralization by monoclonal and bispecific antibodies derived from a Gamma-infected individual
Year: 2023
Type: article
Abstract: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has remained a medical threat due to the evolution of multiple variants that acquire resistance to vaccines and prior infection. Therefore, it is imperative to discover monoclonal antibodies (mAbs) that neutralize a broad range of SARS-CoV-2 variants. A stabilized spike glycoprotein was used to enrich antigen-specific B cells from an individual with a primary Gamma variant infection. Five mAbs selected from those B cells showed considerable neutralizing potency against multiple variants, with COVA309-35 being the most potent against the autologous virus, as well as Omicron BA.1 and BA.2, and COVA309-22 having binding and neutralization activity against Omicron BA.4/5, BQ.1.1, and XBB.1. When combining the COVA309 mAbs as cocktails or bispecific antibodies, the breadth and potency were improved. In addition, the mechanism of cross-neutralization of the COVA309 mAbs was elucidated by structural analysis. Altogether these data indicate that a Gamma-infected individual can develop broadly neutralizing antibodies.
Source: iScience
Authors: Denise Guerra, Tim Beaumont, Laura Radić, Gius Kerster, Karlijn van der Straten, Meng Yuan, Jonathan L. Torres, Wen-Hsin Lee, Hejun Liu, Meliawati Poniman, Ilja Bontjer, Judith A. Burger, Mathieu Claireaux, Tom G. Caniels, Jonne L. Snitselaar, Tom P.L. Bijl, Sabine Kruijer, Gabriel Ozorowski, David Gideonse, Kwinten Sliepen, Andrew B. Ward, Dirk Eggink, Godelieve J. de Bree, Ian A. Wilson, Rogier W. Sanders, Marit J. van Gils
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,150
Funders: U.S. Department of Energy, Bill and Melinda Gates Foundation, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, National Institutes of Health, Office of Science, National Institute of General Medical Sciences, Basic Energy Sciences, Biological and Environmental Research, SLAC National Accelerator Laboratory
Awards: G1229526393, G1286251239, G2371548206, G2456928798, The Scripps Research Institute - to establish a Center of Excellence for structure-guided immunogen design for global health-related problems, G262532246, G303061748, G315621713, G4202012489, G4235786860, G4581610328, G4908923434, G495301720, G498139845, G5570207115, G628751139, G6550344761, G7083997402, G7283024673, G7313278570, G7396808078, G7863156295, G8207748872, G8382000481, G8925327636, A Synchrotron Radiation Structural Biology Resource, Molecular Biophysics Training Program at Stanford, G911061179, G969889393
OpenAlex ID: W4386965245