Mechanistic understanding of the aspect ratio-dependent adjuvanticity of engineered aluminum oxyhydroxide nanorods in prophylactic vaccines

Zhihui Liang; Xin Wang; Ge Yu; Min Li; Shuting Shi; Hang Bao; Chen Chen; Duo Fu; Wei Ma; Changying Xue; Bingbing Sun

doi:10.1016/j.nantod.2022.101445

Mechanistic understanding of the aspect ratio-dependent adjuvanticity of engineered aluminum oxyhydroxide nanorods in prophylactic vaccines

Nano Today. 2022 Apr:43:101445. doi: 10.1016/j.nantod.2022.101445. Epub 2022 Mar 4.

Authors

Zhihui Liang^{1

2}, Xin Wang^{1

2}, Ge Yu^{1

2}, Min Li^{1

2}, Shuting Shi^{1

2}, Hang Bao³, Chen Chen³, Duo Fu^{1

3}, Wei Ma¹, Changying Xue³, Bingbing Sun^{1

2}

Affiliations

¹ State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China.
² School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China.
³ School of Bioengineering, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China.

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.

Keywords: Adjuvants; Aluminum oxyhydroxide; Hepatitis B surface antigen; Humoral immune response; SARS-CoV-2 RBD; Surface hydrophobicity.