tetano
Editor, Senior Moderator
Nat Commun
. 2026 Jul 24;17(1):7266.
doi: 10.1038/s41467-026-76035-z.
JN.1-adapted vaccination is associated with readjustment of ancestral memory B cells toward neutralization within the JN.1 antigenic space
Metodi V Stankov[SUP] #[/SUP][SUP] 1 [/SUP], Matthias Bruhn[SUP] #[/SUP][SUP] 2 [/SUP], Markus Hoffmann[SUP] 3 [/SUP], Abdus Salam[SUP] 2 [/SUP], Amy Eichmann[SUP] 3 [/SUP], Inga Nehlmeier[SUP] 3 [/SUP], Luis A Manthey[SUP] 1 [/SUP], Torsten Witte[SUP] 1 [/SUP], Stefan Pöhlmann[SUP] 3 4 [/SUP], Gerrit Ahrenstorf[SUP] 1 [/SUP], Christine Happle[SUP] 1 5 6 [/SUP], Alexandra Dopfer-Jablonka[SUP] 1 [/SUP], Ulrich Kalinke[SUP] 2 7 8 [/SUP], Georg M N Behrens[SUP] 9 10 11 12 [/SUP]
Affiliations
The antigenic drift of SARS-CoV-2 toward the JN.1 lineage has prompted the development of variant-adapted COVID-19 booster vaccines. However, these boosters are thought to primarily recall pre-existing memory B cells (MBC), raising concerns about their ability to realign the immune response in highly pre-exposed populations. Here we analyze antibody and B cell responses in pre-exposed individuals (n = 42; median 4.5 prior COVID-19 vaccinations; 90% with at least one prior SARS-CoV-2 infection) following vaccination with a JN.1-adapted mRNA vaccine. Vaccination is associated with increased IgG binding and enhanced neutralization of JN.1 and related descendant variants. Longitudinal profiling of antigen-specific MBC shows that Wu01-only and Wu01/JN.1 cross-reactive cells remain dominant, while JN.1-only cells modestly increase by day 21. Single-cell RNA-sequencing of antigen-specific MBC in a representative sub-cohort (n = 7), combined with functional monoclonal antibody analyses, demonstrates that somatic hypermutation (SHM) drives intra-clonotype specialization toward improved JN.1 binding and neutralization. These findings indicate maturation of pre-existing, class-switched MBC rather than substantial de novo recruitment of naïve B cells. In conclusion, JN.1-adapted booster vaccination is associated with refinement of pre-existing MBC repertoires toward the JN.1 antigenic space and with enhanced neutralization of contemporary and antigenically proximate variants.
. 2026 Jul 24;17(1):7266.
doi: 10.1038/s41467-026-76035-z.
JN.1-adapted vaccination is associated with readjustment of ancestral memory B cells toward neutralization within the JN.1 antigenic space
Metodi V Stankov[SUP] #[/SUP][SUP] 1 [/SUP], Matthias Bruhn[SUP] #[/SUP][SUP] 2 [/SUP], Markus Hoffmann[SUP] 3 [/SUP], Abdus Salam[SUP] 2 [/SUP], Amy Eichmann[SUP] 3 [/SUP], Inga Nehlmeier[SUP] 3 [/SUP], Luis A Manthey[SUP] 1 [/SUP], Torsten Witte[SUP] 1 [/SUP], Stefan Pöhlmann[SUP] 3 4 [/SUP], Gerrit Ahrenstorf[SUP] 1 [/SUP], Christine Happle[SUP] 1 5 6 [/SUP], Alexandra Dopfer-Jablonka[SUP] 1 [/SUP], Ulrich Kalinke[SUP] 2 7 8 [/SUP], Georg M N Behrens[SUP] 9 10 11 12 [/SUP]
Affiliations
- PMID: 42498786
- PMCID: PMC13400639
- DOI: 10.1038/s41467-026-76035-z
The antigenic drift of SARS-CoV-2 toward the JN.1 lineage has prompted the development of variant-adapted COVID-19 booster vaccines. However, these boosters are thought to primarily recall pre-existing memory B cells (MBC), raising concerns about their ability to realign the immune response in highly pre-exposed populations. Here we analyze antibody and B cell responses in pre-exposed individuals (n = 42; median 4.5 prior COVID-19 vaccinations; 90% with at least one prior SARS-CoV-2 infection) following vaccination with a JN.1-adapted mRNA vaccine. Vaccination is associated with increased IgG binding and enhanced neutralization of JN.1 and related descendant variants. Longitudinal profiling of antigen-specific MBC shows that Wu01-only and Wu01/JN.1 cross-reactive cells remain dominant, while JN.1-only cells modestly increase by day 21. Single-cell RNA-sequencing of antigen-specific MBC in a representative sub-cohort (n = 7), combined with functional monoclonal antibody analyses, demonstrates that somatic hypermutation (SHM) drives intra-clonotype specialization toward improved JN.1 binding and neutralization. These findings indicate maturation of pre-existing, class-switched MBC rather than substantial de novo recruitment of naïve B cells. In conclusion, JN.1-adapted booster vaccination is associated with refinement of pre-existing MBC repertoires toward the JN.1 antigenic space and with enhanced neutralization of contemporary and antigenically proximate variants.