Work

Somatic Hypermutations Enhance Neutralization Breadth of IGHV3‐53/3‐66 Public Antibodies Against SARS‐CoV‐2 Variants

Year: 2026

Type: article

Abstract: OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continuously evolves to evade antibodies elicited by prior infection or vaccination. Most IGHV3-53/3-66 public antibodies potently neutralize the prototype strain, but show limited activity against recent variants. However, some acquire broad neutralizing activity through accumulation of somatic hypermutations. We assessed whether non-broadly neutralizing IGHV3-53/3-66 antibodies could mature into broadly neutralizing antibodies. METHODS: A series of mutant antibodies was constructed based on the IGHV3-53/3-66 antibodies, 9-105 and K4-66. Neutralizing and binding activities were compared with the original antibodies. RESULTS: Introducing six mutations frequently observed in broadly neutralizing antibodies markedly improved the neutralization and binding of 9-105 against Omicron variants. Introducing Y66F into K4-66 enhanced neutralization of variants including BA.4/5 and JN.1. CONCLUSION: These findings show that mutations within the IGHV3-53/3-66 gene can enhance antibody breadth and potency, suggesting the potential of vaccine strategies to promote the maturation of these widely prevalent public antibodies.

Source: Immunity Inflammation and Disease

DOI: 10.1002/iid3.70527