tetano
Editor, Senior Moderator
Virol Sin
. 2026 Aug 10:S1995-820X(26)00136-7.
doi: 10.1016/j.virs.2026.08.007. Online ahead of print.
Pre-existing hemagglutinin-specific antibody levels are associated with B-cell repertoire maturation and antibody breadth after influenza vaccination
Wei Wang[SUP] 1 [/SUP], Yan Sun[SUP] 1 [/SUP], Qing Liu[SUP] 1 [/SUP], Yidan Xia[SUP] 2 [/SUP], Jing Wang[SUP] 1 [/SUP], Minhao Hu[SUP] 2 [/SUP], Mengyao Kong[SUP] 3 [/SUP], Jun He[SUP] 4 [/SUP], Rongbao Gao[SUP] 5 [/SUP], Yong Gao[SUP] 6 [/SUP]
Affiliations
Repeated influenza exposures generate complex antibody landscapes, yet how pre-existing antibodies are associated with subsequent vaccine responses remains unclear. We longitudinally tracked 21 adults stratified by pre-vaccination neutralizing titers to examine B-cell dynamics using flow cytometry, B cell receptor (BCR) sequencing, and monoclonal antibody characterization. After vaccination, participants with high baseline titers showed a longitudinal increase in the frequency of HA[SUP]+[/SUP]CD27[SUP]-[/SUP]IgD[SUP]+[/SUP] naive-phenotype B cells. BCRs recovered from hemagglutinin (HA)-binding (HA[SUP]+[/SUP]) B cells in the high-titer group displayed lower somatic hypermutation and shorter CDR3s, whereas those recovered from the lower-titer groups showed higher mutation levels and more extensive class switching. Correspondingly, monoclonal antibodies from the high-titer group generally showed narrow reactivity, while those from lower-titer groups showed broader neutralizing activity against historical strains. Clonal tracing further suggested that mAbs from lower-titer groups were more often linked to pre-existing sequences. Together, these findings suggest that pre-existing antibody levels are associated with differences in B-cell repertoire maturation and antibody breadth after influenza vaccination.
Keywords: Antibody breadth; B-cell receptor repertoire; Hemagglutinin (HA); Influenza vaccination; Pre-existing antibodies.
. 2026 Aug 10:S1995-820X(26)00136-7.
doi: 10.1016/j.virs.2026.08.007. Online ahead of print.
Pre-existing hemagglutinin-specific antibody levels are associated with B-cell repertoire maturation and antibody breadth after influenza vaccination
Wei Wang[SUP] 1 [/SUP], Yan Sun[SUP] 1 [/SUP], Qing Liu[SUP] 1 [/SUP], Yidan Xia[SUP] 2 [/SUP], Jing Wang[SUP] 1 [/SUP], Minhao Hu[SUP] 2 [/SUP], Mengyao Kong[SUP] 3 [/SUP], Jun He[SUP] 4 [/SUP], Rongbao Gao[SUP] 5 [/SUP], Yong Gao[SUP] 6 [/SUP]
Affiliations
- PMID: 42575251
- DOI: 10.1016/j.virs.2026.08.007
Repeated influenza exposures generate complex antibody landscapes, yet how pre-existing antibodies are associated with subsequent vaccine responses remains unclear. We longitudinally tracked 21 adults stratified by pre-vaccination neutralizing titers to examine B-cell dynamics using flow cytometry, B cell receptor (BCR) sequencing, and monoclonal antibody characterization. After vaccination, participants with high baseline titers showed a longitudinal increase in the frequency of HA[SUP]+[/SUP]CD27[SUP]-[/SUP]IgD[SUP]+[/SUP] naive-phenotype B cells. BCRs recovered from hemagglutinin (HA)-binding (HA[SUP]+[/SUP]) B cells in the high-titer group displayed lower somatic hypermutation and shorter CDR3s, whereas those recovered from the lower-titer groups showed higher mutation levels and more extensive class switching. Correspondingly, monoclonal antibodies from the high-titer group generally showed narrow reactivity, while those from lower-titer groups showed broader neutralizing activity against historical strains. Clonal tracing further suggested that mAbs from lower-titer groups were more often linked to pre-existing sequences. Together, these findings suggest that pre-existing antibody levels are associated with differences in B-cell repertoire maturation and antibody breadth after influenza vaccination.
Keywords: Antibody breadth; B-cell receptor repertoire; Hemagglutinin (HA); Influenza vaccination; Pre-existing antibodies.