Aluminum Hydroxide Adjuvant in Vaccines: Mechanism and Optimization

Overview of Aluminum Hydroxide Adjuvant

Aluminum hydroxide adjuvant has been an integral component of vaccines for several decades. Chemically, aluminum hydroxide adjuvant exists in the form of aluminum hydroxyl groups, and their hydroxyl groups can donate or accept protons, thus appearing as amphoteric compounds. This adjuvant plays a crucial role in enhancing the immunogenicity of vaccines, thereby eliciting robust and long-lasting protective immune responses.

The Role and Mechanism of Aluminum Hydroxide Adjuvant

Although aluminum hydroxide adjuvants are widely used, the exact mechanism by which they enhance immune responses is not fully understood. Aluminum hydroxide adjuvants function by stimulating and modulating the immune response to vaccine antigens. To date, researchers' explanations of the immune-stimulating mechanisms of aluminum hydroxide adjuvants include [1]:

• The repository effect
• Pro-phagocytic effect
• Activation of the pro-inflammatory NLRP3 pathway
• Promotion of innate immune responses
• elicitation of acquired immune response
• Complement activation

In Which Vaccines Has Aluminum Hydroxide Adjuvant Been Used?

Aluminum hydroxide adjuvants have been employed in a variety of vaccines, including those against infectious diseases and certain allergens. Notable examples include vaccines against hepatitis B, diphtheria, tetanus, and pertussis (DTaP), and human papillomavirus (HPV) vaccines.

The following table lists some of the applications of aluminum hydroxide adjuvants in common vaccine excipients in the United States.

Useful Link

It is always recommended that you check the vaccine package insert on the official FDA website.

Vaccines Licensed for Use in the United States

Safety Concerns of Aluminum Hydroxide Adjuvant

There are ongoing debates and research regarding their safety, particularly regarding potential links to adverse effects such as allergies, autoimmune diseases, and neurological conditions. Currently, the aluminum hydroxide adjuvant in some U.S.-licensed vaccines has proven safety over more than sixty years of use. Research shows that people who follow recommended vaccination schedules are exposed to lower amounts of aluminum, which is less easily absorbed by the body. According to an F DA study, the risk to humans (even infants) from occasional exposure to vaccines containing aluminum adjuvants remains extremely low.

Body burden contributions of aluminum from diet and vaccines. [2]

Improvement of Aluminum Hydroxide Adjuvant

The development of appropriate formulations using aluminum adjuvants requires a detailed understanding of the physical and chemical properties of the vaccine antigen, and the interaction of the antigen with the adjuvant. Excipients such as salts, buffers, and tonicity regulators are important factors influencing antigen-adjuvant interactions. In addition, aluminum hydroxide nanoparticles exhibit stronger vaccine adjuvant activity than traditional aluminum hydroxide microparticles.

Optimization of aluminum adjuvants. [3]

For example, Xinran Li et al. synthesized 112 nm aluminum hydroxide nanoparticles and used ovalbumin and B. anthracis protective antigen protein as model antigens. Protein antigens adsorbed on aluminum hydroxide nanoparticles were found to induce stronger antigen-specific antibody responses than the same protein antigens adsorbed on conventional aluminum hydroxide microparticles around 9.3 μm.

Aluminum hydroxide nanoparticles with a stronger vaccine adjuvant activity. [4]

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References

1. Peng He, et al. Hum Vaccin Immunother. 2015, 11(2), 477-488.
2. Mitkus, Robert J., et al. Vaccine 29.51 (2011), 9538-9543.
3. HogenEsch H, et al. npj Vaccines, 2018, 3(1), 51.
4. Li X, et al. Journal of controlled release, 2014, 173, 148-157.

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