Vaccine antigens

Mechanisms of action and types of adjuvants

Adjuvants solve the problem of insufficient immunogenicity of purified antigens. Their main task is to create a focus of inflammation and activate antigen-presenting cells (APCs) by relying on the recognition of pathogen-associated molecular patterns (PAMPs). Without innate immune stimulation, a full-fledged adaptive response is not formed.

The composition of the adjuvant strictly determines the pathway of the immune reaction:

• Freund's adjuvants: a historically important group that is now banned due to high reactogenicity. Incomplete Freund's adjuvant (lanolin, mineral oil, emulsifier) creates a depot for the slow release of the antigen and is used in repeated immunizations. Complete Freund's adjuvant additionally contains BCG (Mycobacterium bovis strain). Mycobacteria powerfully stimulate dendritic cells, which is critically important for antigen presentation to naive T cells during the primary response.
• Pro-inflammatory stimuli: microorganisms and BCG direct the response along the cellular pathway involving Th1 lymphocytes.
• Mineral salts: aluminum potassium sulfate stimulates the thymus-dependent humoral response via Th2 cells. This is the most frequent and safest option in modern approved vaccines.
• Liposomes: lipid vesicles that deliver antigenic material into the endosomal compartment of the cell.
• ISCOM systems (Immune stimulatory complexes): unique complexes of an antigen, detergent, and the plant glycoside Quil A. They are capable of penetrating the cell membrane, delivering viral proteins directly into the cytosol. There, the antigen is chopped by the proteasome into peptides, which go via the TAP transporter into the endoplasmic reticulum. The result is the incorporation of epitopes into MHC-I molecules and potent stimulation of cytotoxic CD8+ T cells.

Classification of vaccines by antigen nature

Depending on the technology used to produce the antigenic material, several generations of vaccine preparations are distinguished:

1. Live attenuated: the pathogen is stripped of virulence but retains immunogenicity. This is achieved through cultivation under unfavorable conditions or targeted genetic modification (targeted deletion of the virulence gene followed by virus "reassembly"). They are highly effective but carry the risk of reversion to the wild type. Examples: BCG, measles, rubella, and herpes vaccines, and the live oral Sabin polio vaccine. Jenner's smallpox vaccine, which operates on the principle of cross-reactivity (cowpox virus protects against human smallpox), also belongs here.
2. Inactivated (killed): the causative agent is inactivated physically or chemically (e.g., with formalin). They are safer, but stimulate immunity more weakly. Examples: vaccines against pertussis, cholera, typhoid fever, rabies, and the inactivated Salk polio vaccine.
3. Antitoxic: the active substance is an inactivated bacterial toxin (anatoxin/toxoid) in a complex with an adjuvant. Used against diphtheria and tetanus.
4. Recombinant: created using genetic engineering methods. The protective antigen gene is cut out using restriction enzymes and placed under a viral promoter in a plasmid. This recombinant DNA is then introduced into a safe vector (e.g., cowpox virus). Used for the prophylaxis of influenza, herpes, and vesicular stomatitis.

Synthetic, DNA, and anti-idiotypic vaccines

The search for the ideal balance between safety and immunogenicity has led to the creation of entirely artificial preparations.

• Synthetic vaccines: developed in the 1970s (R.V. Petrov, R.M. Khaitov). They represent a pure peptide epitope conjugated with a carrier-adjuvant. Initially, toxic polyelectrolytes were used, but they were subsequently replaced by polyoxidonium (azoximer bromide). Based on this, the Grippol vaccine was created in 1988, where the polymer is bound to the surface antigens of the influenza virus (hemagglutinin and neuraminidase of H1N1, H3N2, and B strains). Synthetic vaccines are also being developed against salmonellosis, foot-and-mouth disease, and yersiniosis.
• DNA vaccines: an experimental direction. These are bacterial vectors (plasmids) carrying genes for the required antigens. The preparation is administered intramuscularly, after which the host's cells express the foreign protein themselves. The exact mechanisms triggering immunity in the muscles are still being studied (e.g., hepatitis B vaccines).
• Anti-idiotypic vaccines: an exotic approach where antibodies are used instead of an antigen. The active site of such an anti-idiotypic antibody spatially mimics the configuration of the original pathogen's epitope. Theoretically, this solves the problem when obtaining a native antigen is difficult. In practice, efficacy has proven low (experience with the hepatitis B vaccine), and for now, this remains merely an elegant scientific concept.

Class and exam questions

What else to study on this topic

• Mechanisms of antigen processing in the cytosol: the role of proteasomes and TAP transporters.
• Structure and functions of pathogen-associated molecular patterns (PAMPs) in the activation of innate immunity.
• Molecular engineering: stages of creating recombinant plasmids and vectors.
• Pharmacological properties and immunomodulatory action of polyoxidonium.
• The phenomenon of cross-antigenic reactivity using the example of poxviruses.

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

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