Self-assembled aluminum oxyhydroxide nanorices with superior suspension stability for vaccine adjuvant

Abstract

The suspension stability of aluminum-based adjuvant (Alum) plays an important role in determining the Alum-antigen interaction and vaccine efficacy. Inclusion of excipients has been shown to stabilize antigens in vaccine formulations. However, there is no mechanistic study to tune the characteristics of Alum for improved suspension stability. Herein, a library of self-assembled rice-shaped aluminum oxyhydroxide nanoadjuvants i.e., nanorices (NRs), was synthesized through intrinsically controlled crystallization and atomic coupling-mediated aggregations. The NRs exhibited superior suspension stability in both water and a saline buffer. After adsorbing hepatitis B surface antigen (HBsAg) virus-like particles (VLPs), human papillomavirus virus (HPV) VLPs, or bovine serum albumin, NR-antigen complexes exhibited less sedimentation. Further mechanistic study demonstrated that the improved suspension stability was due to intraparticle aggregations that led to the reduction of the surface free energy. By using HBsAg in a murine vaccination model, NRs with higher aspect ratios elicited more potent humoral immune responses. Our study demonstrated that engineered control of particle aggregation provides a novel material design strategy to improve suspension stability for a diversity of biomedical applications.