tetano
Editor, Senior Moderator
Immun Inflamm Dis
. 2026 Sep;14(9):e70527.
doi: 10.1002/iid3.70527.
Takeo Kuwata 1 , Kyo Okazaki 2 , Hiroshi Morioka 2 , Yu Kaku 3 4 , Mikiko Shimizu 1 , Yoshimi Maruyama 1 , Ahmed K Hamdy 1 ; Genotype to Phenotype Japan (G2P‐Japan) Consortium; Tateki Suzuki 5 , Takao Hashiguchi 5 , Kei Sato 6 , Shuzo Matsushita 1
Affiliations Expand
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.
Keywords: SARS‐CoV‐2; neutralizing antibody; public antibody; variant.
. 2026 Sep;14(9):e70527.
doi: 10.1002/iid3.70527.
Somatic Hypermutations Enhance Neutralization Breadth of IGHV3-53/3-66 Public Antibodies Against SARS-CoV-2 Variants
Takeo Kuwata 1 , Kyo Okazaki 2 , Hiroshi Morioka 2 , Yu Kaku 3 4 , Mikiko Shimizu 1 , Yoshimi Maruyama 1 , Ahmed K Hamdy 1 ; Genotype to Phenotype Japan (G2P‐Japan) Consortium; Tateki Suzuki 5 , Takao Hashiguchi 5 , Kei Sato 6 , Shuzo Matsushita 1
Affiliations Expand
- PMID: 42747156
- DOI: 10.1002/iid3.70527
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.
Keywords: SARS‐CoV‐2; neutralizing antibody; public antibody; variant.