Tuning Mechanoreceptor Signaling Enhances the Adjuvant Effect of Biomaterial Vaccines

Increasing hydrogel crosslinking further slows antigen release and increases mechanical rigidity. Herein, we tested whether upon enhancing mechanical stiffness of vaccine microporous annealed particle (Vax-MAP), a granular hydrogel vaccine platform could provide enhanced adjuvant effects through activation of Piezo1 and/or the Yap/Taz mechanotransduction pathways in immune cells.

Indeed, regardless of the presence of an antigen, increasing hydrogel rigidity through polymer crosslinking dramatically enhanced innate immune cell recruitment and activation to Vax-MAP hydrogel implants. Deletion of either Yap/Taz or Piezo1 in myeloid cells impaired this stiffness-induced immune cell recruitment in response to antigen-free formulations. Pharmacological inhibition of Yap/Taz, but not global deletion of Piezo1, reduced the enhanced production of low and high affinity antibody responses to stiffer Vax-MAP formulations.