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

doi:10.1016/j.isci.2022.104456

Mechanistic elucidation of freezing-induced surface decomposition of aluminum oxyhydroxide adjuvant

iScience. 2022 May 23;25(6):104456. doi: 10.1016/j.isci.2022.104456. eCollection 2022 Jun 17.

Authors

Jiahuan Li^{1

2}, Ge Yu^{1

2}, Zhihui Liang^{1

2}, Min Li^{1

2}, Chen Chen³, Xin Li², Yiyang Guo², Cheng Yang⁴, Yang Liu^{1

2}, Caiqiao Zhang⁵, Weiting Zhang⁵, Jiaxu Liu², Xuehu Ma², 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.
⁴ School of Chemistry, Dalian University of Technology, 2 Linggong Road, 116024 Dalian, China.
⁵ NCPC Genetech Biotechnology Co., Ltd., Shijiazhuang 050035, P. R. China.

Abstract

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.

Keywords: Biotechnology; Inorganic materials; Materials chemistry; Materials science.