Chemical Nature and Classification
Most adjuvants are substances completely foreign to the human or animal host. They vary widely in origin and chemical structure. The main classes used in vaccine development include:
- Mineral salts: Aluminum hydroxide and aluminum phosphate gels.
- Bacterial components: Extracts of BCG (which serve as the basis for Complete Freund's Adjuvant), as well as inactivated Bordetella pertussis organisms.
- Complex organic compounds: Lipopolysaccharides (LPS), protein-LPS complexes, and muramyl dipeptide (MDP) along with its derivatives.
- Lipids and emulsifiers: Lanolin, Arlacel.
- Inflammatory agents: Turpentine, saponins.
- Polymeric compounds.
Mechanism of Action: Effects on the Antigen
Adjuvants act through a combination of mechanisms. The first pathway involves altering the physicochemical properties of the co-administered antigen.
Through adsorption or chemical conjugation with a polymeric carrier, aggregation of the antigen occurs. Soluble antigens are converted into a particulate form. This structural alteration has a significant immunological consequence: aggregated particulate antigens are captured and presented far more efficiently by phagocytes and antigen-presenting cells. Furthermore, adjuvants can shift the character of the immune response, potentially transforming a thymus-dependent antigen into a thymus-independent one.
Mechanism of Action: Effects on the Host Organism
The second pathway involves direct action on the host tissues at the injection site. Vaccines containing adjuvants are often described as depot vaccines.
In response to the injection of a foreign, often irritant substance, a local inflammatory reaction develops, ultimately forming a fibrous capsule. This creates a depot where the antigen persists for an extended period.
The gradual, sustained release of antigen from this depot into the systemic circulation produces a summation effect. For the immune system, this mimics repeated low-dose exposures, reducing the need for frequent booster vaccinations.
Additionally, adjuvants directly stimulate immunity by enhancing the proliferation of immunocompetent cells and augmenting the synthesis of specific protective antibodies.
Efficacy of Adjuvant Use
The addition of adjuvants generally enhances antigen immunogenicity several-fold. However, the most pronounced effect is observed with soluble protein toxoids.
When soluble molecular protein antigens (such as tetanus, botulinum, or diphtheria toxoids) are combined with an appropriate adjuvant, the immunogenicity of the preparation increases up to 100-fold compared to administering the unformulated antigen.