19n01, a broadly neutralizing antibody against omicron BA.1, BA.2, BA.4/5, and other SARS-CoV-2 variants of concern

Melissa García-Vega, Edgar A. Melgoza-González, Sofía Hernández-Valenzuela, Diana Hinojosa-Trujillo, Mónica Reséndiz-Sandoval, Mara Anais Llamas-Covarrubias, Martín Loza-López, Olivia Valenzuela, Alan Soto-Gaxiola, Miguel A. Hernández-Oñate, Verónica Mata-Haro, Irene Cassaniti, Josè Camilla Sammartino, Alessandro Ferrari, Luca Simonelli, Mattia Pedotti, Rui Sun, Fanglei Zuo, Fausto Baldanti, Luca VaraniHarold Marcotte, Qiang Pan-Hammarström, Jesús Hernández*

*Autor correspondiente de este trabajo

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This study reports the isolation and characterization of a human monoclonal antibody (mAb) called 19n01. This mAb was isolated by using single-cell RNAseq of B cells from donors infected with the ancestral strain. This mAb possesses a potent and broad capacity to bind and neutralize all previously circulating variants of concern (VOCs), including Omicron sublineages BA.1, BA.2, and BA.4/5. The pseudovirus neutralization assay revealed robust neutralization capacity against the G614 strain, BA.1, BA.2, and BA.4/5, with inhibitory concentration (IC50) values ranging from 0.0035 to 0.0164 μg/mL. The microneutralization assay using the G614 strain and VOCs demonstrated IC50 values of 0.013–0.267 μg/mL. Biophysical and structural analysis showed that 19n01 cross-competes with ACE2 binding to the receptor-binding domain (RBD) and the kinetic parameters confirmed the high affinity against the Omicron sublineages (KD of 61 and 30 nM for BA.2 and BA.4/5, respectively). These results suggest that the 19n01 is a remarkably potent and broadly reactive mAb.

Idioma originalInglés
Número de artículo106562
EstadoPublicada - 21 abr. 2023

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