Toll-like receptor 9 agonist IMO-2125 rapidly reshapes the B-cell receptor repertoire in non-human primates

CpG oligodeoxynucleotides activate Toll-like receptor 9 (TLR9) and are used as vaccine adjuvants and immunotherapies, but their in vivo effects on the B-cell receptor (BCR) repertoire are incompletely defined. We administered the TLR9 agonist IMO-2125 to Indian rhesus macaques and African green monkeys and profiled peripheral-blood BCR repertoires at baseline, 24 h, 72 h, and 1 week. Light-chain clonotype and lineage diversity decreased after dosing, with the strongest lineage redistribution at 72 h. Most affected lineages decreased in frequency or clonotype number while showing increased mutation rates. Enriched heavy-chain lineages were biased toward mutated IgA and IgG and were consistent with memory- and effector-like B cells. The heavy-chain repertoire was comparatively stable, and responses differed in magnitude between species. These findings indicate that IMO-2125 rapidly reshapes the circulating BCR repertoire, most plausibly through selective redistribution of antigen-experienced B cells rather than broad clonal expansion.