Unlocking binding properties of single-domain antibodies targeting the polymeric immunoglobulin receptor to enhance mucosal enrichment of IgG against respiratory syncytial virus - PubMed
4 hours ago
- #respiratory syncytial virus
- #mucosal immunity
- #bispecific antibody
- The study focuses on enhancing mucosal immunity by improving IgG transport across mucosal barriers using single-domain antibodies (VHH) targeting the polymeric immunoglobulin receptor (pIgR).
- IgA naturally translocates across mucosal barriers via pIgR, but IgG does not, despite being preferred for therapeutic development due to its well-characterized functions.
- Anti-pIgR VHH-Fc molecules were screened, revealing correlations between binding parameters (KD and koff) and transcytosis efficiency, with pH-dependent binding identified as a potential influencing factor.
- A bispecific antibody (bsAb) was engineered by fusing an anti-pIgR VHH to an IgG targeting respiratory syncytial virus (RSV), enabling efficient transcytosis while retaining RSV neutralization capabilities.
- The bsAb successfully transcytosed across pIgR-expressing MDCK cells and a human airway mucosal barrier model, demonstrating a novel strategy for mucosal delivery of biologics.