Main Types of Vaccines
The classification of vaccine products is based on the nature of the antigen used and the method of its production:
- Live Attenuated. Contain pathogens whose virulence has been artificially reduced while preserving their ability to induce an immune response. They are highly effective because microorganisms replicate (self-replicate) in the human body. However, there is a minimal risk of reverting to the pathogenic form (reversion). Examples: BCG (for tuberculosis), the Sabin polio vaccine, measles and rubella vaccines.
- Inactivated (Killed). The pathogen is killed chemically (e.g., with formalin) or physically without destroying protective antigens. They are completely safe regarding the development of the infection, but less effective than live counterparts. Examples: the Salk polio vaccine, rabies and typhoid vaccines.
- Antitoxic (Toxoids). Used when the main factor of bacterial pathogenicity is its toxin. The toxin is detoxified (converted into a toxoid), stripping away its poisonous properties while retaining antigenicity. Examples: prevention of diphtheria and tetanus.
Modern Biotechnological Approaches
Molecular engineering is now actively used to create safer and more targeted preparations:
- Recombinant (Vector). Virulence genes are removed from the pathogen's genome, and genes encoding desired (protective) antigens are inserted into a safe carrier virus. Often, the vaccinia virus serves as such a vector, which itself stimulates immunity.
- DNA Vaccines. Consist of a plasmid carrying the target gene. Following intramuscular injection, the host's cells begin expressing the pathogen's antigen themselves (e.g., HBs antigen in hepatitis B prevention).
- Synthetic. Artificially assembled complexes where B-cell epitopes are linked to T-cell epitopes and innate immunity activators. Despite their technological advancement, they currently show weak immunogenicity due to gaps in our understanding of the nature of antigenicity.
- Idiotypic. An experimental approach where anti-idiotypic antibodies mimicking the spatial structure of the pathogen's epitope are administered instead of the antigen.
Combination Preparations and the Role of Adjuvants
To address the issue of insufficient immunogenicity of purified antigens and toxoids, adjuvants are used—substances (mineral alums, saponins) administered alongside the vaccine to enhance the body's response.
Vaccines are frequently combined to protect a person against multiple infections simultaneously. A classic example of a combination product is the DTaP vaccine. It is supplied in liquid form, contains an aluminum hydroxide adjuvant, and includes diphtheria and tetanus toxoids, as well as killed Bordetella pertussis bacteria. The cellular pertussis component is most frequently responsible for the pro-inflammatory side effects of the preparation (local reactions, fever).
Complications and Legal Aspects
Vaccination is a state-regulated procedure. In the Russian Federation, the Federal Law on Immunoprophylaxis is in effect, and the National Immunization Schedule includes routine protection with 7 vaccines against 11 infections. The first vaccinations (BCG and hepatitis B) are administered in the first days of life, DTaP at 3 months, and booster doses are given several years later to maintain the effect.
Contraindications include immunodeficiencies, severe reactions to previous doses, and allergies to components. Serious complications (toxic, allergic reactions, nervous system damage, or development of an infection from a live vaccine) are extremely rare—occurring at a rate of about 1 in 1,000,000 cases.
The Challenge of Developing an HIV Vaccine
Despite the eradication of smallpox and a dramatic decrease in the incidence of measles and poliomyelitis, science remains powerless against diseases such as plague, syphilis, malaria, and AIDS.
Developing an HIV vaccine is one of vaccinology's most complex challenges. Two factors hinder this:
- The colossal mutagenicity of the virus (especially its surface glycoproteins, which are the main target for antibodies).
- Direct destruction and depletion of CD4+ T lymphocytes (T-helper cells), without which the initiation of adaptive immunity is impossible.
However, the existence of individuals with natural resistance to HIV and patients whose immune systems can strongly slow disease progression gives scientists hope for successfully developing a vaccine in the future.
Briefly: answers to topical questions
What are the molecular and cellular mechanisms of the adjuvant action of aluminum hydroxide?
The mechanism of aluminum hydroxide's adjuvant action involves antigen deposition and enhancement of phagocytosis with the formation of a Th2-dependent immune response. An inflammatory reaction occurs at the injection site, forming a fibrous capsule where the antigen persists for a long time. The gradual release of antigen from the depot acts as repeated stimulation of the immune system (summation effect). In addition, direct stimulation of the immune system occurs:
- Cell activation — direct activation of proliferation of immunocompetent cells.
- Protein synthesis — enhanced synthesis of protective proteins.
What are subunit and split vaccines, and for which infections are they used?
Subunit and split vaccines are highly purified inactivated preparations used for the specific prevention of influenza.
| Characteristic | Subunit vaccines | Split vaccines |
|---|---|---|
| Principle of creation | Fractionation of killed microorganisms | Disruption of the virion with removal of envelope lipids |
| Composition | Include only protective antigens (hemagglutinin and neuraminidase) | Full set of viral antigens without lipids |
| Goal of application | Induction of specific immunity | Reduction of the pyrogenic effect through high purification |
Which conditions are absolute contraindications for administering live vaccines?
Absolute contraindications to the administration of live vaccines include:
- Primary immunodeficiency.
- Malignant neoplasms.
- Pregnancy.
- Post-kidney transplantation status.
During methotrexate therapy, vaccination with live vaccines must strictly be avoided.
Which viral vectors are used as platforms for creating recombinant vaccines?
Viral vectors used to create recombinant vaccines include:
- Vaccinia virus — a classic carrier virus into which a recombinant plasmid carrying the protective antigen gene is inserted.
- Modified vaccinia Ankara (MVA) — a vector promoting the generation of humoral and cellular immune responses.
Genes encoding pathogen protective antigens can also be integrated into the genome of a safe microbial carrier.
The composition of DTaP is reflected right in its name: D — Diphtheria toxoid, P — Pertussis (killed bacteria), D — Diphtheria, T — Tetanus (toxoid).
Class and exam questions
Why live vaccines are considered more effective than killed ones?
Live attenuated microorganisms are capable of replication (self-replication) within the human body. This provides prolonged and physiological antigenic stimulation, leading to more robust and lasting immunity.
Why vaccines against viral infections are not administered to newborns?
Antiviral vaccines (e.g., against measles, mumps, and rubella) are administered at 12–15 months of age. If given earlier, the vaccine virus may be neutralized by maternal protective antibodies circulating in the child's blood during the first year of life.
How cross-antigenic reactivity works using smallpox as an example
Historically, E. Jenner used the cowpox virus, which causes only mild illness in humans. Due to antigenic similarity (cross-reactivity), the immune system learns to recognize and combat the lethal human smallpox virus as well, forming reliable protection.
What else to study on this topic
- Molecular mechanisms of viral attenuation (targeted genome modification)
- Role of PAMPs (pathogen-associated molecular patterns) in innate immunity activation
- Subunit and chemical vaccines: fractionation and synthesis technologies
- Causes of adverse effects and reactogenicity of combination vaccines
- Mucosal vaccines (oral and nasal): application prospects
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