Aluminum Phosphate Adjuvant: Enhancing Vaccine Efficacy and Safety

Overview of Aluminum Phosphate Adjuvant

Aluminum salt adjuvants have been used safely in vaccines for more than 70 years. Aluminum phosphate adjuvant is one of the most common aluminum adjuvants, which can enhance immunogenicity and improve vaccine design.

In fact, aluminum phosphate adjuvant is not a single substance, but an aluminum hydroxyphosphate complex. Aluminum phosphate adjuvant does not have a fixed molecular formula, but its approximate molecular formula is [Al(OH)x(PO₄)y].

The degree of displacement of hydroxyl groups by phosphate groups depends on the reactants and precipitation conditions and their isoelectric point. Generally speaking, the isoelectric point of aluminum phosphate adjuvant is 5.0, it exists in anionic form in a solution with pH 7.4, and is a good adsorbent for cationic antigens.

The Role and Mechanism of Aluminum Phosphate Adjuvant

The primary function of aluminum phosphate adjuvants is to potentiate and modulate the immune response generated by vaccines. By stimulating the innate immune system, these adjuvants activate dendritic cells, leading to improved antigen presentation and subsequent activation of adaptive immune responses. This ultimately results in the generation of robust and long-lasting immune memory against the target pathogen.

The exact mechanisms by which aluminum phosphate adjuvant enhances immune responses are still not fully understood. The immunostimulatory mechanisms of aluminum phosphate currently proposed by researchers mainly include:

• Depot Effect
• Recruitment of Immune Cells
• Enhancement of Antigen Uptake by Antigen Presenting Cells (APCs)
• Activation of NLRP3 Inflammasome Pro-Inflammatory Signaling Pathway
• Stimulatory Potential of Humoral Immune Responses

Immunostimulatory mechanism of aluminum phosphate adjuvant. [1]

In Which Vaccines Have Aluminum Phosphate Adjuvants Been Used?

Aluminum phosphate adjuvants have been used in a variety of vaccines, including but not limited to DT (Sanofi), DTaP (Daptacel), DTaP-IPV (Quadracel), Hep A/Hep B (Twinrix), and Meningococcal (MenB – Trumenba). Below is a list of some of the aluminum phosphate adjuvanted vaccines licensed for use in the United States and their aluminum content.

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

Aluminum Phosphate Safety Issues

There is ongoing debate and research surrounding the safety of aluminum adjuvants, including aluminum phosphate. Some studies suggest a potential link between aluminum adjuvants and certain health conditions, such as autoimmune disorders or neurological disorders. However, regulatory agencies like the U.S. Food and Drug Administration (FDA) and the World Health Organization (WHO) consider aluminum adjuvants to be safe for use in vaccines.

Improvement of Aluminum Phosphate Vaccine Adjuvant

In order to solve the problem that aluminum salt adjuvants have a weak ability to assist in inducing cellular immunity and can cause injection site reactions, more improved methods for adjuvants need to be developed.

Improvement of aluminum phosphate formula

Amorphous aluminum hydroxyphosphate sulfate adjuvant (AAHS) has been developed as a preferential incorporation or alternative to AP in a variety of vaccine formulations.

Development of nano-aluminum phosphate adjuvants

The effect of aluminum phosphate adjuvant can be effectively enhanced by changing its particle size and shape. For example, amorphous aluminum hydroxyphosphate nanoparticles (AAHP) synthesized by chemical precipitation show significantly enhanced immunostimulatory potential.

Amorphous aluminum hydroxyphosphate nanoparticles. [2]

Development of composite adjuvants containing aluminum phosphate

In general, aluminum adjuvants can enhance type II immune responses but do not induce type I immune responses. To induce both type I and type II immune responses, additional ingredients can be added to the aluminum adjuvant to create a synergistic effect. For example, the AS04 adjuvant, consisting of an aluminum adjuvant and the TLR4 agonist monophosphate A (MPL), was the first combination adjuvant approved for use in human vaccines, including HPV and hepatitis B vaccines.

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References

1. Ting Zhang, et al. Pharmaceutics, 2023, 15(6), 1756.
2. Liang Z, et al. Biomaterials, 2021, 275, 120960.

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