Chiral Aluminum Oxyhydroxide Supraparticles as Adjuvants

Abstract Aluminum‐based adjuvants dominate global vaccine formulations owing to their proven efficacy in humoral immunity induction. However, their inherent limitations in activating cellular immunity pose critical challenges for vaccine development. In this study, chiral flower‐like aluminum oxyhydroxide (AlOOH) supraparticles (SPs) are synthesized via a one‐pot hydrothermal method using cysteine (Cys) enantiomers as chiral ligands, achieving a g‐factor of 0.004. L‐AlOOH SPs (L‐SPs) demonstrate significantly greater enhancement in dendritic cell (DC) maturation and antigen cross‐presentation efficiency compared to D‐AlOOH SPs (D‐SPs), indicating its potential as an adjuvant. Mechanistic studies reveal that L‐SPs enter DCs via Toll‐like receptor 2 (TLR2), thereby enhancing NOD‐like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation. In vivo experiments show that L‐SPs generate 21.59‐fold higher OVA‐specific antibody titers than commercial aluminum adjuvants. Further studies show that L‐SPs, after mixed with H9N2 virus proteins, enhance influenza virus antibody titers by 15.28‐fold, with sustained protection, confirming its translational potential. This study demonstrates the performance of chiral AlOOH SPs to simultaneously amplify humoral and cellular immunological responses, entering it as a promising next‐generation adjuvant for cancer immunotherapy and pandemic preparedness.