@article{68f799f8e93f450b969198d68c0e2084,
title = "Broad SARS-CoV-2 neutralization by monoclonal and bispecific antibodies derived from a Gamma-infected individual",
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.",
keywords = "Immunology, Structural biology, Virology",
author = "Denise Guerra and Tim Beaumont and Laura Radi{\'c} and Gius Kerster and {van der Straten}, Karlijn and Meng Yuan and Torres, {Jonathan L.} and Wen-Hsin Lee and Hejun Liu and Meliawati Poniman and Ilja Bontjer and Burger, {Judith A.} and Mathieu Claireaux and Caniels, {Tom G.} and Snitselaar, {Jonne L.} and Bijl, {Tom P. L.} and Sabine Kruijer and Gabriel Ozorowski and David Gideonse and Kwinten Sliepen and Ward, {Andrew B.} and Dirk Eggink and {de Bree}, {Godelieve J.} and Wilson, {Ian A.} and Sanders, {Rogier W.} and {van Gils}, {Marit J.}",
note = "Funding Information: This work was supported by a Netherlands Organisation for Scientific Research (NWO) Vici Grant (no. 91818627 ) to R.W.S, by the Fondation Dormeur, Vaduz (R.W.S and M.J.vG.), and by the Bill and Melinda Gates Foundation INV-004923 (I.A.W., A.B.W.). Funding Information: We thank the public health services (GGD) in the Netherlands for the help in contacting participants. We are also thankful to the participants of the COSCA study for the contribution to this research. We thank Robyn Stanfield for assistance in data collection. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy , Office of Science , Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515 . The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health , National Institute of General Medical Sciences ( P30GM133894 ). Funding Information: We thank the public health services (GGD) in the Netherlands for the help in contacting participants. We are also thankful to the participants of the COSCA study for the contribution to this research. We thank Robyn Stanfield for assistance in data collection. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences (P30GM133894). This work was supported by a Netherlands Organisation for Scientific Research (NWO) Vici Grant (no. 91818627) to R.W.S, by the Fondation Dormeur, Vaduz (R.W.S and M.J.vG.), and by the Bill and Melinda Gates Foundation INV-004923 (I.A.W. A.B.W.). Conceptualization: R.W.S. M.J.vG. T.B. G.J.dB. Funding acquisition: I.A.W. R.W.S. M.J.vG. G.J.dB. Investigation: D.G. T.B. L.R. G.K. M.Y. J.L.T. W-H.L. H.L. M.P. I.B. J.A.B. J.L.S. S.K. D.G. Methodology: L.R. K.S. M.C. T.G.C. D.E. G.O. A.B.W. Resources: L.R. G.J.dB. K.vdS. D.E. T.G.C, I.B. Supervision: G.O. A.B.W. T.B. K.S. M.C. I.A.W. R.W.S. M.J.vG. Writing – original draft: D.G. T.B. R.W.S. M.J.vG. Writing – review & editing: all authors. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
month = oct,
day = "20",
doi = "https://doi.org/10.1016/j.isci.2023.108009",
language = "English",
volume = "26",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier",
number = "10",
}