iScience (Apr 2023)
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
Affiliations
- Melissa García-Vega
- Laboratorio de Inmunología, Centro de Investigación en Alimentación y Desarrollo, A.C. Hermosillo, Sonora, Mexico
- Edgar A. Melgoza-González
- Laboratorio de Inmunología, Centro de Investigación en Alimentación y Desarrollo, A.C. Hermosillo, Sonora, Mexico
- Sofía Hernández-Valenzuela
- Laboratorio de Inmunología, Centro de Investigación en Alimentación y Desarrollo, A.C. Hermosillo, Sonora, Mexico
- Diana Hinojosa-Trujillo
- Laboratorio de Inmunología, Centro de Investigación en Alimentación y Desarrollo, A.C. Hermosillo, Sonora, Mexico
- Mónica Reséndiz-Sandoval
- Laboratorio de Inmunología, Centro de Investigación en Alimentación y Desarrollo, A.C. Hermosillo, Sonora, Mexico
- Mara Anais Llamas-Covarrubias
- Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Japan
- Martín Loza-López
- Laboratory of Functional Analysis in silico, The University of Tokyo, Shirokanedai, Tokyo, Japan
- Olivia Valenzuela
- Departamento de Ciencias Químico Biológicas, División de Ciencias de la Salud, Universidad de Sonora, Hermosillo, Sonora, Mexico
- Alan Soto-Gaxiola
- Hospital General del Estado de Sonora “Dr. Ernesto Ramos Bours”, Secretaria de Salud del Estado de Sonora, Hermosillo, Sonora, Mexico
- Miguel A. Hernández-Oñate
- Laboratorio de Fisiología y Biología Molecular de Plantas, Centro de Investigación en Alimentación y Desarrollo, A.C. Hermosillo, Sonora, Mexico
- Verónica Mata-Haro
- Laboratorio de Microbiología e Inmunología, Centro de Investigación en Alimentación y Desarrollo, A.C. Hermosillo, Sonora, Mexico
- Irene Cassaniti
- Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- Josè Camilla Sammartino
- Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- Alessandro Ferrari
- Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- Luca Simonelli
- Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland
- Mattia Pedotti
- Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland
- Rui Sun
- Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
- Fanglei Zuo
- Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
- Fausto Baldanti
- Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostics and Pediatric Sciences, University of Pavia, Pavia, Italy
- Luca Varani
- Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Bellinzona, Switzerland
- Harold Marcotte
- Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
- Qiang Pan-Hammarström
- Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
- Jesús Hernández
- Laboratorio de Inmunología, Centro de Investigación en Alimentación y Desarrollo, A.C. Hermosillo, Sonora, Mexico; Corresponding author
- Journal volume & issue
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Vol. 26,
no. 4
p. 106562
Abstract
Summary: 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.
