X-Ray Investigating the Aging Process of Aluminum Hydroxide Adjuvant in Protein-Based Vaccine Formulations Over a Short Period

Halvagar, Mohammad Reza; Zali, Mohammad; Zali, Sara; Najafi Mobara, Mahdieh; Bahemmat, Samira

doi:10.22092/ari.2025.367994.3463

X-Ray Investigating the Aging Process of Aluminum Hydroxide Adjuvant in Protein-Based Vaccine Formulations Over a Short Period

Articles in Press

Document Type : Original Articles

Authors

¹ Faculty member Department of Inorganic Chemistry, Chemistry and Chemical Engineering Research Center of Iran, PO Box 14335-186, Tehran, Iran

² Chemistry Department, Razi Vaccine & Serum Research Institute

³ Quality Assurance Department, Razi Vaccine & Serum Research Institute

⁴ Department of Inorganic Chemistry, Chemistry and Chemical Engineering Research Center of Iran

10.22092/ari.2025.367994.3463

Abstract

X-Ray Investigating the Aging Process of Aluminum Hydroxide Adjuvant in Vaccine Formulations

Abstract:
Nearly a century has passed since Glenny and colleagues introduced aluminum-based adjuvants. Over this extensive period, billions of doses of human and veterinary vaccines incorporating these adjuvants have been produced, ensuring both human health and food security. Aluminum-based adjuvants have played a pivotal role during epidemics, allowing scientists to accelerate vaccine development and save lives. Continuous research conducted by institutions worldwide has substantiated the safety and efficacy of aluminum-based adjuvants, establishing them as the gold standard. Consequently, any new adjuvant must be benchmarked against aluminum-based adjuvants and demonstrate substantial advantages to gain regulatory approval.
This study investigates the aging process of aluminum hydroxide under controlled variations in temperature, pH, and ionic strength. The physicochemical properties of each adjuvant, including pH changes during thermal treatments over different durations and in the sterilization process, protein adsorption capacity for each sample, particle size, and X-ray diffraction (XRD) patterns, are analyzed. These findings not only enhance our understanding of adjuvant stability but also provide valuable insights for determining their optimal shelf life.
The study demonstrates that the best storage conditions for the adjuvant, with minimal impact from the aging process, are a low pH (pH=5) and higher ionic strength. It was also confirmed that innovative measures, such as reducing the sterilization cycle, stirring the samples after sterilization, and rapidly cooling them afterward, can prevent crystal growth and even produce smaller particle sizes with higher adjuvanticity. This is significant as previous studies had reported a decline in adjuvanticity following sterilization.

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