Exploiting FcRn engagement of an albumin-CpG oligonucleotide covalent conjugate for potent TLR9 immune induction.

ABSTRACT: CpG-oligodeoxynucleotide (CpG ODN)-based Toll-like receptor (TLR) agonists are promising immunostimulatory adjuvants; however, low entry into TLR-rich cellular endosomal compartments and poor lymphatic accumulation limit clinical translation. In this work, we introduce a recombinant human serum albumin (rHA)-CpG ODN covalent conjugate (rHA-CpG) designed to exploit the neonatal Fc receptor (FcRn)-driven albumin cellular sorting pathway to maximize CpG delivery into TLR9-rich endosomes and accumulate in lymph nodes. Site-selective conjugation of CpG to albumin cysteine 34, distant from its main FcRn-binding interface, resulted in a retained pH-dependent human FcRn binding, and receptor-driven endosomal trafficking in a cellular recycling assay. Induction of tumor necrosis factor (TNF) secret

SUBMITTER: Pilati D 

PROVIDER: S-EPMC12148431 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature