TY - JOUR
T1 - 19n01, a broadly neutralizing antibody against omicron BA.1, BA.2, BA.4/5, and other SARS-CoV-2 variants of concern
AU - García-Vega, Melissa
AU - Melgoza-González, Edgar A.
AU - Hernández-Valenzuela, Sofía
AU - Hinojosa-Trujillo, Diana
AU - Reséndiz-Sandoval, Mónica
AU - Llamas-Covarrubias, Mara Anais
AU - Loza-López, Martín
AU - Valenzuela, Olivia
AU - Soto-Gaxiola, Alan
AU - Hernández-Oñate, Miguel A.
AU - Mata-Haro, Verónica
AU - Cassaniti, Irene
AU - Sammartino, Josè Camilla
AU - Ferrari, Alessandro
AU - Simonelli, Luca
AU - Pedotti, Mattia
AU - Sun, Rui
AU - Zuo, Fanglei
AU - Baldanti, Fausto
AU - Varani, Luca
AU - Marcotte, Harold
AU - Pan-Hammarström, Qiang
AU - Hernández, Jesús
N1 - Publisher Copyright:
© 2023 The Author(s)
PY - 2023/4/21
Y1 - 2023/4/21
N2 - 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.
AB - 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.
KW - Immunology
KW - Transcriptomics
KW - Virology
UR - http://www.scopus.com/inward/record.url?scp=85152374476&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2023.106562
DO - 10.1016/j.isci.2023.106562
M3 - Artículo
C2 - 37063467
AN - SCOPUS:85152374476
SN - 2589-0042
VL - 26
JO - iScience
JF - iScience
IS - 4
M1 - 106562
ER -