iScience


. 2023 Sep 22;26(10):108009.
doi: 10.1016/j.isci.2023.108009. eCollection 2023 Oct 20. Broad SARS-CoV-2 neutralization by monoclonal and bispecific antibodies derived from a Gamma-infected individual

Denise Guerra 1 2 , Tim Beaumont 1 2 , Laura Radić 1 2 , Gius Kerster 1 2 , Karlijn van der Straten 1 2 3 , Meng Yuan 4 , Jonathan L Torres 4 , Wen-Hsin Lee 4 , Hejun Liu 4 , Meliawati Poniman 1 2 , Ilja Bontjer 1 2 , Judith A Burger 1 2 , Mathieu Claireaux 1 2 , Tom G Caniels 1 2 , Jonne L Snitselaar 1 2 , Tom P L Bijl 1 2 , Sabine Kruijer 1 2 , Gabriel Ozorowski 4 , David Gideonse 5 , Kwinten Sliepen 1 2 , Andrew B Ward 4 , Dirk Eggink 1 2 5 , Godelieve J de Bree 2 3 , Ian A Wilson 4 6 , Rogier W Sanders 1 2 7 , Marit J van Gils 1 2



AffiliationsAbstract

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.

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