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Title | Broad SARS-CoV-2 neutralization by monoclonal and bispecific antibodies derived from a Gamma-infected individual. |
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Journal, issue, pages | iScience, Vol. 26, Issue 10, Page 108009, Year 2023 |
Publish date | Oct 20, 2023 |
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 / |
PubMed 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 ...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. |
External links | iScience / PubMed:37841584 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 3.7 - 25.0 Å |
Structure data | EMDB-28850: SARS-CoV-2 Gamma 6P Mut7 S + COVA309-3 Fab EMDB-28851: SARS-CoV-2 Gamma 6P Mut7 S + COVA309-10 Fab EMDB-28852: SARS-CoV-2 Omicron 6P S + COVA309-35 Fab EMDB-28853: SARS-CoV-2 Gamma 6P Mut7 + S COVA309-38 Fab PDB-8f0i: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Antibody / SARS-CoV-2 / coronavirus / RBD / COVID-19 / IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex |