19n01, a Broadly Neutralizing Antibody Against Omicron BA.1, BA.2, BA.4/5, and Other SARS-CoV-2 Variants of Concern

The constant evolution of SARS-CoV-2 has provoked the emergence of new variants with mutations that evade the neutralizing response of antibodies. The last variant, Omicron, has several mutations, of which the Spike protein is the leading cause of this evasion. Identifying new monoclonal antibodies (mAbs) that efficiently neutralize a new variant will help generate efficient treatments based on mAbs and reveal unique virus characteristics. In this study, we report the isolation and characterization of a human monoclonal antibody 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 original strain, BA.1, BA.2, and BA.4/5, with IC50 values ranging from 0.0002 to 0.0021 µg/mL. The microneutralization assay using the ancestral virus and VOCs demonstrated IC50 values of 0.013 to 0.267 µg/mL, and in the case of BA.2 and BA.5, the IC50 values were 0.0685, and 0.0445 µg/mL, respectively. Biophysical and structural analysis showed that 19n01 cross-competes with ACE2 binding to the 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 epitope may be located in a highly conserved RBD region, making it an ideal candidate as a therapeutic agent for COVID-19 against current VOCs.Funding Information: This research was funded by Consejo Nacional de Ciencia y Tecnología (CONACyT), grant number 312677 and by The European Union’s Horizon 2020 research and innovation program (ATAC, 101003650).Declaration of Interests: MGV, MRS, EAMG, VMH, and JH are coinventors of patent applications describing the neutralizing mAbs. The other authors declare no competing interests.Ethics Approval Statement: The study was evaluated and approved by the Ethics Committee of the CIAD, AC (C.E.I./012-2/2020), and all patients signed informed consent forms.