iScience (Oct 2023)

Broad SARS-CoV-2 neutralization by monoclonal and bispecific antibodies derived from a Gamma-infected individual

  • 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

Journal volume & issue
Vol. 26, no. 10
p. 108009

Abstract

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Summary: 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.

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