RBD-based enzyme-linked immunosorbent assay (ELISA) screening resulted in the identification of 92 SARS-CoV-2–specific mAbs (fig. In total, we sorted 804 SARS-CoV-2 RBD fluorescent probe binding class-switched B cells, amplified 398 (~50%) paired heavy- (HC) and light-chain (LC) antibody gene sequences, and successfully cloned and expressed 208 antibodies ( Fig. S1, A to C) for the generation of SARS-CoV-2 RBD-specific mAbs. We selected five individuals (table S1) who had high SARS-CoV-2 RBD binding titers, high neutralization titers to live SARS-CoV-2 WA.1, and had detectable frequencies of RBD-specific memory B cells (fig. We previously evaluated the humoral immune responses in 42 COVID-19–recovered individuals who had experienced mild symptoms after the ancestral Wuhan strain (WA.1) transmission in the year 2020 ( 15). The discovery of 002-S21F2 and the broadly neutralizing epitope it targets have timely implications for developing a broad range of therapeutic and vaccine interventions against SARS-CoV-2 variants including Omicron sublineages.
Structural studies of 002-S21F2 in complex with spike trimers of Omicron and WA.1 showed that it targets a conformationally conserved epitope on the outer face of RBD (class 3 surface) outside the ACE2-binding motif, thereby providing a mechanistic insights for its broad neutralization activity. In this study, by characterizing several human monoclonal antibodies (mAbs) isolated from single B cells of the COVID-19–recovered individuals in India who experienced ancestral Wuhan strain (WA.1) of SARS-CoV-2 during early stages of the pandemic, we found a receptor binding domain (RBD)–specific mAb 002-S21F2 that has rare gene usage and potently neutralized live viral isolates of SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, and Omicron sublineages (BA.1, BA.2, BA.2.12.1, BA.4, and BA.5) with IC 50 ranging from 0.02 to 0.13 μg/ml. Suthar, Rafi Ahmed, Eric Ortlund, Amit Sharma, Kaja Murali-Krishna, and Anmol Chandele Show Fewer Davis, Jens Wrammert, Sucheta Godbole, Amy R. Roback, Grace Mantus, Pawan Kumar Goel, Manju Rahi, Carl W. Davis-Gardner, Venkata Viswanadh Edara, Susanne Linderman, Kaustuv Nayak, Kritika Dixit, Pragati Sharma, Prashant Bajpai, Vanshika Singh, Filipp Frank, Narayanaiah Cheedarla, Hans P. Sanjeev Kumar, Anamika Patel, Lilin Lai, Chennareddy Chakravarthy, Rajesh Valanparambil, Elluri Seetharami Reddy, Kamalvishnu Gottimukkala, … Show All …, Meredith E.
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