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Publication Abstract from PubMed

The decrease of antibody efficacy to mutated SARS-CoV-2 spike RBD explains the breakthrough infections and reinfections by Omicron variants. Here, we analyzed broadly neutralizing antibodies isolated from long-term hospitalized convalescent patients of early SARS-CoV-2 strains. One of the antibodies named NCV2SG48 is highly potent to broad SARS-CoV-2 variants including Omicron BA.1, BA.2, and BA.4/5. To reveal the mode of action, we determined the sequence and crystal structure of the Fab fragment of NCV2SG48 in a complex with spike RBD from the original, Delta, and Omicron BA.1. NCV2SG48 is from a minor V(H) but the multiple somatic hypermutations contribute to a markedly extended binding interface and hydrogen bonds to interact with conserved residues at the core receptor-binding motif of RBD, which efficiently neutralizes a broad spectrum of variants. Thus, eliciting the RBD-specific B cells to the longitudinal germinal center reaction confers potent immunity to broad SARS-CoV-2 variants emerging one after another.

Structural basis of spike RBM-specific human antibodies counteracting broad SARS-CoV-2 variants.,Shitaoka K, Higashiura A, Kawano Y, Yamamoto A, Mizoguchi Y, Hashiguchi T, Nishimichi N, Huang S, Ito A, Ohki S, Kanda M, Taniguchi T, Yoshizato R, Azuma H, Kitajima Y, Yokosaki Y, Okada S, Sakaguchi T, Yasuda T Commun Biol. 2023 Apr 11;6(1):395. doi: 10.1038/s42003-023-04782-6. PMID:37041231^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.