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 Varani; Harold Marcotte; Qiang Pan-Hammarström; Jesús Hernández

doi:10.1016/j.isci.2023.106562

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

iScience. 2023 Apr 21;26(4):106562. doi: 10.1016/j.isci.2023.106562. Epub 2023 Apr 1.

Authors

Melissa García-Vega¹, Edgar A Melgoza-González¹, Sofía Hernández-Valenzuela¹, Diana Hinojosa-Trujillo¹, Mónica Reséndiz-Sandoval¹, Mara Anais Llamas-Covarrubias², Martín Loza-López³, Olivia Valenzuela⁴, Alan Soto-Gaxiola⁵, Miguel A Hernández-Oñate⁶, Verónica Mata-Haro⁷, Irene Cassaniti⁸, Josè Camilla Sammartino⁸, Alessandro Ferrari⁸, Luca Simonelli⁹, Mattia Pedotti⁹, Rui Sun¹⁰, Fanglei Zuo¹⁰, Fausto Baldanti^{8

11}, Luca Varani⁹, Harold Marcotte¹⁰, Qiang Pan-Hammarström¹⁰, Jesús Hernández¹

Affiliations

¹ Laboratorio de Inmunología, Centro de Investigación en Alimentación y Desarrollo, A.C. Hermosillo, Sonora, Mexico.
² Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Japan.
³ Laboratory of Functional Analysis in silico, The University of Tokyo, Shirokanedai, Tokyo, Japan.
⁴ Departamento de Ciencias Químico Biológicas, División de Ciencias de la Salud, Universidad de Sonora, Hermosillo, Sonora, Mexico.
⁵ Hospital General del Estado de Sonora "Dr. Ernesto Ramos Bours", Secretaria de Salud del Estado de Sonora, Hermosillo, Sonora, Mexico.
⁶ Laboratorio de Fisiología y Biología Molecular de Plantas, Centro de Investigación en Alimentación y Desarrollo, A.C. Hermosillo, Sonora, Mexico.
⁷ Laboratorio de Microbiología e Inmunología, Centro de Investigación en Alimentación y Desarrollo, A.C. Hermosillo, Sonora, Mexico.
⁸ Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
⁹ Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland.
¹⁰ Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
¹¹ Department of Clinical, Surgical, Diagnostics and Pediatric Sciences, University of Pavia, Pavia, Italy.

Abstract

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 (K_D 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.

Keywords: Immunology; Transcriptomics; Virology.