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

doi:10.1016/j.isci.2023.108009

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

iScience. 2023 Sep 22;26(10):108009. doi: 10.1016/j.isci.2023.108009. eCollection 2023 Oct 20.

Authors

Denise Guerra^{1

2}, Tim Beaumont^{1

2}, Laura Radić^{1

2}, Gius Kerster^{1

2}, Karlijn van der Straten^{1

2

3}, Meng Yuan⁴, Jonathan L Torres⁴, Wen-Hsin Lee⁴, Hejun Liu⁴, 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 Ozorowski⁴, David Gideonse⁵, Kwinten Sliepen^{1

2}, Andrew B Ward⁴, 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}

Affiliations

¹ Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands.
² Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, the Netherlands.
³ Amsterdam UMC, location University of Amsterdam, Department of Internal Medicine, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands.
⁴ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁵ Center for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), 3721 MA Bilthoven, the Netherlands.
⁶ The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁷ Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA.

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.

Grants and funding

P30 GM133894/GM/NIGMS NIH HHS/United States