Mechanistic elucidation of freezing-induced surface decomposition of aluminum oxyhydroxide adjuvant
Jiahuan Li,
Ge Yu,
Zhihui Liang,
Min Li,
Chen Chen,
Xin Li,
Yiyang Guo,
Cheng Yang,
Yang Liu,
Caiqiao Zhang,
Weiting Zhang,
Jiaxu Liu,
Xuehu Ma,
Changying Xue,
Bingbing Sun
Affiliations
Jiahuan Li
State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China; School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China
Ge Yu
State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China; School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China
Zhihui Liang
State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China; School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China
Min Li
State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China; School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China
Chen Chen
School of Bioengineering, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China
Xin Li
School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China
Yiyang Guo
School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China
Cheng Yang
School of Chemistry, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China
Yang Liu
State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China; School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China
Caiqiao Zhang
NCPC Genetech Biotechnology Co., Ltd., Shijiazhuang 050035, P. R. China
Weiting Zhang
NCPC Genetech Biotechnology Co., Ltd., Shijiazhuang 050035, P. R. China
Jiaxu Liu
School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China
Xuehu Ma
School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China
Changying Xue
School of Bioengineering, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China
Bingbing Sun
State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China; School of Chemical Engineering, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China; Corresponding author
Summary: The freezing-induced aggregation of aluminum-based (Alum) adjuvants has been considered as the most important cause of reduced vaccine potency. However, the intrinsic properties that determine the functionality of Alum after freezing have not been elucidated. In this study, we used engineered aluminum oxyhydroxide nanoparticles (AlOOH NPs) and demonstrated that cryogenic freezing led to the mechanical pressure-mediated reduction of surface hydroxyl. The sugar-based surfactant, octyl glucoside (OG), was demonstrated to shield AlOOH NPs from the freezing-induced loss of hydroxyl content and the aggregation through the reduction of recrystallization-induced mechanical stress. As a result, the antigenic adsorption property of frozen AlOOH NPs could be effectively protected. When hepatitis B surface antigen (HBsAg) was adjuvanted with OG-protected frozen AlOOH NPs in mice, the loss of immunogenicity was inhibited. These findings provide insights into the freezing-induced surface decomposition of Alum and can be translated to design of protectants to improve the stability of vaccines.
