tetano
Editor, Senior Moderator
Front Immunol
. 2026 Aug 25:17:1906350.
doi: 10.3389/fimmu.2026.1906350. eCollection 2026.
Luanfeng Lin # 1 2 , Luxuan Yang # 3 , Yulei Sun # 4 , Jiayan Li 3 , Yinying Lu 3 , Hongyu Wang 4 , Yabo Mi 3 , Liangjiu Zhang 3 , Binhuang Sun 4 , Xinyi Yu 4 , Tianmei Yu 4 , Xiaoyu Zhao 3 , Jingwen Ai 4 , Wenhong Zhang 1 3 4 5
Affiliations Expand
SARS-CoV-2 Omicron evolution continues to erode antibody-mediated immunity, but whether infection with antigenically distinct lineages simply amplifies pre-existing memory or redirects humoral recognition toward newly evolved antigenic space remains unclear. Here, we analyzed paired early- and convalescent-phase plasma and whole-blood samples from individuals with sequencing-confirmed BF.7 or JN.1 infection. Integrated neutralization profiling, antigenic cartography, and bulk B cell receptor (BCR) repertoire analysis revealed lineage-associated humoral trajectories. Both breakthrough infections increased cross-variant neutralization, but their updated humoral profiles were not equivalent. BF.7 breakthrough infection broadly boosted neutralization from a BA.5-related background, whereas JN.1 breakthrough infection produced greater gains against BA.2.86, JN.1, and KP.2 and shifted humoral recognition toward late-Omicron antigenic space. Neutralization remained branch-structured, with BQ.1.1 and KP.2 acting as persistent escape nodes within the BA.2/BA.5-related and BA.2.86/JN.1-related branches, respectively. This humoral updating paralleled changes in IGH clonotype counts, repertoire diversity, V/J gene usage, isotype composition, and V-J pairing, whereas major CDR3 length distributions and sequence-logo patterns remained largely conserved. Overall, these findings indicate that antigenically distinct Omicron breakthrough infections generate non-equivalent humoral recall trajectories: BF.7 exposure preferentially reinforced BA.5-related antibody recognition, whereas JN.1 exposure more effectively redirected recognition toward BA.2.86/JN.1-derived variants.
Keywords: BCR repertoire; Omicron; SARS-CoV-2; antigenic cartography; neutralization breadth.
. 2026 Aug 25:17:1906350.
doi: 10.3389/fimmu.2026.1906350. eCollection 2026.
Comparative analysis of immune escape and BCR repertoire remodeling after Omicron BF.7 and JN.1 infections
Luanfeng Lin # 1 2 , Luxuan Yang # 3 , Yulei Sun # 4 , Jiayan Li 3 , Yinying Lu 3 , Hongyu Wang 4 , Yabo Mi 3 , Liangjiu Zhang 3 , Binhuang Sun 4 , Xinyi Yu 4 , Tianmei Yu 4 , Xiaoyu Zhao 3 , Jingwen Ai 4 , Wenhong Zhang 1 3 4 5
Affiliations Expand
- PMID: 42712620
- PMCID: PMC13550182
- DOI: 10.3389/fimmu.2026.1906350
Abstract
SARS-CoV-2 Omicron evolution continues to erode antibody-mediated immunity, but whether infection with antigenically distinct lineages simply amplifies pre-existing memory or redirects humoral recognition toward newly evolved antigenic space remains unclear. Here, we analyzed paired early- and convalescent-phase plasma and whole-blood samples from individuals with sequencing-confirmed BF.7 or JN.1 infection. Integrated neutralization profiling, antigenic cartography, and bulk B cell receptor (BCR) repertoire analysis revealed lineage-associated humoral trajectories. Both breakthrough infections increased cross-variant neutralization, but their updated humoral profiles were not equivalent. BF.7 breakthrough infection broadly boosted neutralization from a BA.5-related background, whereas JN.1 breakthrough infection produced greater gains against BA.2.86, JN.1, and KP.2 and shifted humoral recognition toward late-Omicron antigenic space. Neutralization remained branch-structured, with BQ.1.1 and KP.2 acting as persistent escape nodes within the BA.2/BA.5-related and BA.2.86/JN.1-related branches, respectively. This humoral updating paralleled changes in IGH clonotype counts, repertoire diversity, V/J gene usage, isotype composition, and V-J pairing, whereas major CDR3 length distributions and sequence-logo patterns remained largely conserved. Overall, these findings indicate that antigenically distinct Omicron breakthrough infections generate non-equivalent humoral recall trajectories: BF.7 exposure preferentially reinforced BA.5-related antibody recognition, whereas JN.1 exposure more effectively redirected recognition toward BA.2.86/JN.1-derived variants.
Keywords: BCR repertoire; Omicron; SARS-CoV-2; antigenic cartography; neutralization breadth.