Suspension stability of aluminum-based adjuvants

Abstract

Aluminum hydroxyphosphate (AAHP) and aluminum oxyhydroxide (AlOOH) are widely used adjuvants in human vaccines. However, vaccines formulated with aluminum-based adjuvants often exist as suspensions that can experience phase separation, spontaneous aggregation, layering, and settling, potentially compromising their immunogenic efficacy. Despite their widespread use, research into the suspension stability of aluminum-based adjuvants remains limited. In this study, we synthesized a series of aluminum hydroxyphosphate and AlOOH nanoparticles and systematically evaluated their suspension stabilities under various conditions. Our findings reveal that for aluminum hydroxyphosphate, particle size and ζ potential are the primary determinants of suspension stability, aligning with DLVO theory and Stokes’ law. For AlOOH, the suspension stability is governed by a combination of factors, including particle size, ζ potential, surface free energy (SFE) and hydrophobicity. Notably, the commercial adjuvant Alhydrogel® exhibited low suspension stability compared to our synthesized AlOOH nanoparticles, a result attributed to its high SFE. Furthermore, under specific formulation conditions, aluminum-based adjuvants with enhanced suspension stability improved the suspension stability of their corresponding adjuvant-antigen complexes. This study provides a foundation for optimizing the suspension stability of aluminum-based adjuvants and offers valuable insights for their rational design and transportation in vaccine development.