Adjuvants

Classification and origin

By their nature and composition, adjuvants are divided into several main groups:

• Natural components: lipopolysaccharides (LPS), peptidoglycans, nucleic acids with CpG motifs, and attenuated microorganisms (e.g., Mycobacterium bovis strains in the BCG vaccine).
• Synthetic substances: polyelectrolytes and specialized polymers.
• Cytokines: immune system regulatory molecules.
• Complex delivery systems: liposomes, dendrimers, and targeted delivery complexes.

Main mechanisms of action

The addition of an adjuvant solves the most complex challenge of vaccination — the efficient presentation of antigen to naive T lymphocytes. This is achieved through the following mechanisms:

1. Formation of an antigen depot. The delayed release of the preparation prolongs the duration of its effect on the immune system.
2. Direct stimulating effect. The adjuvant provokes local inflammation and activates innate immunity mechanisms, particularly antigen-presenting cells (APCs).
3. Optimal delivery. Vector transport of the antigen to specific compartments of target cells.

How adjuvant composition determines the type of immunity

Depending on the system used, the immune system develops different types of responses:

• Th2-dependent (humoral) response: predominantly induced by mineral adjuvants (aluminium and calcium salts or hydroxide).
• Th1-dependent (cellular inflammatory) response: develops in response to proinflammatory stimuli — BCG or other microbial components.
• Cytotoxic (CD8+) response: requires the introduction of the antigen directly into the cytosol. For this purpose, ISCOM systems (Immune stimulatory complexes) are used. In these, the antigen is bound to micelles of the glycoside Quil A. Once in the cytosol, the antigen is degraded by the proteasome, transported via the TAP system into the endoplasmic reticulum, and incorporated into MHC-I molecules.
• To deliver the antigen into the endosomal compartment, liposomes — lipid vesicles containing the antigen — are used.

Freund's adjuvants: the historical standard

This group of adjuvants possesses colossal immunogenicity but is prohibited in clinical practice due to severe adverse effects. They are used exclusively in experiments:

• Incomplete Freund's adjuvant: an emulsion of mineral oil, lanolin, and an emulsifier. It creates a long-lasting depot and is used to maintain immunity during repeat immunizations (Th2 response).
• Complete Freund's adjuvant: BCG is added to the components of the incomplete adjuvant. Mycobacteria potently stimulate dendritic cells, which is why the preparation is used to effectively initiate a primary immune response (Th1 response).

Synthetic and alternative approaches

Since the primary requirement for vaccines is absolute safety (especially in mass use among children), the concept of fully synthetic vaccines emerged in the 1970s. The idea consisted in creating peptides conjugated with a polymer carrier.

Initially, polyelectrolytes were used, but due to their low biodegradability, polyoxidonium (azoximer bromide) — a safe synthetic polymer — became the drug of choice. The Grippol vaccine was created on its basis, in which influenza virus hemagglutinin and neuraminidase are bound to polyoxidonium.

Experimental directions:

• DNA vaccines: intramuscular administration of bacterial vectors containing protective antigen genes, where expression of the required proteins occurs.
• Anti-idiotypic vaccines: a concept in which the active center of an anti-idiotypic antibody spatially mimics the epitope of the original pathogen. Despite the elegance of the idea, the efficacy of such vaccines (e.g., against hepatitis B) has so far proven to be low.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Processing and presentation of antigens in MHC class I and II molecules.
• The role of dendritic cells in adjuvant recognition.
• Mechanisms of formation of Th1- and Th2-dependent immune responses.
• Physicochemical properties and metabolism of polyoxidonium.
• The principle of the idiotypic network and anti-idiotypic antibodies.

Other topics in the section "Immunity in defense and damage of the organism. Pathology of immunity"

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