Aluminum-based adjuvants have long been utilized in vaccine formulations due to their immunostimulatory properties and strong safety record. The most commonly used aluminum adjuvants are aluminum hydroxide (AH) and aluminum phosphate (AP) salts, both of which are synthesized as hydrated nanoparticles. While the efficacy and safety of aluminum adjuvants are well-established, the precise mechanism behind their adjuvant action remains elusive. One of the theories states that aluminum adjuvants could act as depots for antigen proteins, enabling their slow release, which in turn enhances their uptake by antigen-presenting cells. As both AH and AP nanoparticles are known to form aggregates, characterizing the porous structures within these aggregates is pivotal to a comprehensive understanding of the depot theory.
In this study, Small-Angle X-ray Scattering was performed to investigate the arrangement of AH and AP nanoparticles. SAXS results suggest that the morphology of aluminum nanoparticles has a pronounced effect on the spatial organization of pores formed within their aggregates. Notably, nanoparticles with lower aspect ratios tend to form bigger and more open porous structures. To further probe the effects of aluminum nanoparticle morphologies on the porosity formed within their aggregates, we synthesized a wide range of AH and AP nanoparticles with distinctly different shapes and sizes. We then characterized the porosity within their aggregates, as well as the retention of antigen proteins within these porous networks. Collectively, we demonstrate the powerful use of SAXS for the in situ characterization of the porous structures within aluminum adjuvants. Our results not only shed light on the mechanism of action of aluminum adjuvants but also could benefit the rational development of nanoparticle-based adjuvants with enhanced performance.

Illustration of the porous Aluminum adjuvant aggregates and their morphology-driven antigen release mechanism.

Amy Xu

Louisiana State University

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