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

• Published in: iScience Vol. 26; no. 4; p. 106562
• Main Authors: García-Vega, Melissa, Melgoza-González, Edgar A., Hernández-Valenzuela, Sofía, Hinojosa-Trujillo, Diana, Reséndiz-Sandoval, Mónica, Llamas-Covarrubias, Mara Anais, Loza-López, Martín, Valenzuela, Olivia, Soto-Gaxiola, Alan, Hernández-Oñate, Miguel A., Mata-Haro, Verónica, Cassaniti, Irene, Sammartino, Josè Camilla, Ferrari, Alessandro, Simonelli, Luca, Pedotti, Mattia, Sun, Rui, Zuo, Fanglei, Baldanti, Fausto, Varani, Luca, Marcotte, Harold, Pan-Hammarström, Qiang, Hernández, Jesús
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.04.2023; The Author(s); Elsevier
• Subjects: Immunology; Medicin och hälsovetenskap; Transcriptomics; Virology; Transcriptomics; Immunology; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106562

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. [Display omitted] •Single-cell RNAseq was done in B cells from donors infected with the ancestral strain•Selected mAbs were produced and characterized against SARS-COV-2 VOCs•19n01 mAb neutralizes SARS-CoV-2 VOCs, including Omicron BA.1, BA.2, and BA.4/5•19n01 mAb cross-competes with ACE2 binding to the RBD Immunology; Virology; Transcriptomics