Mechanistic understanding of the aspect ratio-dependent adjuvanticity of engineered aluminum oxyhydroxide nanorods in prophylactic vaccines. (April 2022)

• Record Type: Journal Article
• Authors: Liang, Zhihui; Wang, Xin; Yu, Ge; Li, Min; Shi, Shuting; Bao, Hang; Chen, Chen; Fu, Duo; Ma, Wei; Xue, Changying; Sun, Bingbing
• Is Part Of: Nano today. Volume 43(2022)
• Publication Date: 2022-04
• Subjects: Aluminum oxyhydroxide -- Adjuvants -- Surface hydrophobicity -- Humoral immune response -- SARS-CoV-2 RBD -- Hepatitis B surface antigen; Nanotechnology -- Periodicals; Nanosciences -- Périodiques; 620.505
• DOI: 10.1016/j.nantod.2022.101445
• Languages: English
• ISSNs: 1748-0132

Abstract

Abstract: Aluminum oxyhydroxide (AlOOH) adjuvants are widely used in human vaccines. However, the interaction mechanisms at the material-bio interface, and further understandings on physicochemical property-dependent modulation of the immune responses still remain uncertain. Herein, a library of AlOOH nanorods with well-defined aspect ratios is designed to explore the mechanisms of adjuvanticity. The aspect ratios of AlOOH nanorods were demonstrated to be intrinsically modulated by the hydroxide supersaturation level during crystal growth, leading to the differences in surface free energy (SFE). As a result, higher aspect ratio AlOOH nanoadjuvants with lower SFE exhibited more hydrophobic surface, resulting in more membrane depolarization, cellular uptake and dendritic cell (DC) activation. By using hepatitis B surface antigen (HBsAg) virus-like particles (VLPs) or SARS-CoV-2 spike protein receptor-binding domain (RBD) as model antigens, AlOOH nanorods with higher aspect ratio were determined to elicit more potent humoral immune responses, which could be attributed to the enhanced DC activation and the efficient antigen trafficking to the draining lymph nodes. Our findings highlight the critical role of aspect ratio of AlOOH nanorods in modulating adjuvanticity, and further provide a design strategy for engineered nanoadjuvants for prophylactic vaccines. Graphical Abstract: ga1 Highlights: AlOOH nanorods with different aspect ratios could be intrinsically modulated by the hydroxide supersaturation level during crystal growth. Higher aspect ratio AlOOH nanorods with lower surface free energy (SFE) exhibit more hydrophobic surface, leading to more significant nano-cell interactions. AlOOH nanorods with higher aspect ratios elicited enhanced humoral immune responses, which were attributed to more effective DC activation in draining lymph nodes.