Virulence variability and strain derivation
Virulence is a phenotypic manifestation of a microorganism's genotype. It is not an absolute constant and can change under the influence of physical, chemical, or biological environmental factors.
To create vaccine strains, the process of attenuation—artificial reduction of virulence—is used. The main mechanisms for obtaining such strains include prolonged cultivation of the pathogen on artificial nutrient media or its repeated passage through the organism of poorly susceptible animals (or through cell cultures). If a microorganism completely loses its pathogenic properties, this indicates a change in its genotype. It is precisely these non-pathogenic variants that form the basis for live vaccines.
The reverse process—an increase in virulence—is also possible in nature. It occurs during the passage of the pathogen through highly susceptible animals, and at the genetic level, it is caused by mutations, recombinations, or lysogenic processes.
In addition, microorganisms possess mechanisms of adaptive variability. These include bacterial L-transformation, cyst formation in spirochetes, synthesis of a protective capsule upon entering a macroorganism, and temperature-dependent synthesis of pathogenicity factors (e.g., invasion proteins in yersinia or the Vi antigen in S. Typhi).
Requirements for vaccine strains and immunization rules
The main condition for the effectiveness of any vaccine is an exact match between the antigenic structure of the vaccine strains and the epidemic variants currently circulating. Since some viruses are prone to frequent mutations, the composition of preparations must be regularly updated. Vaccines must include "prognostically" relevant strains; otherwise, in the event of major changes in the viral antigenic structure, the vaccination will fail to provide protection.
Routine specific prevention is carried out at least one month before the start of the epidemic season (usually in September–October). Vaccination is primarily indicated for the following risk groups:
- Children and individuals over 65 years of age.
- Patients with metabolic syndrome, chronic pulmonary and cardiovascular diseases.
- Women planning pregnancy during a surge in incidence.
- Individuals with a high occupational risk of infection (healthcare workers).
Classification of vaccines (using influenza prevention as an example)
Depending on the processing technology of the vaccine strain, several types of preparations are distinguished:
- Live allantoic vaccines (administered intranasally or subcutaneously). They induce the most comprehensive immunity, including local protection of mucous membranes.
- Inactivated whole-virion vaccines ("killed"). They contain an intact inactivated virion. Important: like live allantoic preparations, they are strictly contraindicated in patients with chicken egg protein allergy.
- Split vaccines (fractionated). They contain a full set of viral antigens, but the lipids of the outer viral envelope have been removed. This significantly reduces the allergic effect.
- Subvirion vaccines (subunit, polymer-subunit, or "chemical"). These are the most purified preparations, as they contain only isolated protective antigens (hemagglutinin and neuraminidase).
Features of stable virus strains (using measles as an example)
Unlike rapidly mutating pathogens, some viruses possess high antigenic stability. For example, the RNA-genomic measles virus (family Paramyxoviridae, genus Morbillivirus) is monoserotypic—all circulating strains globally belong to a single serological variant.
The virus itself is extremely labile in the external environment: it is rapidly inactivated by insolation (direct sunlight), high temperatures, detergents, and standard disinfectants. However, its biotechnological application is highly successful: repeated passage on cell and tissue cultures yields reliable attenuated strains. They are completely non-pathogenic yet retain high immunogenicity and serve as the basis for the production of live measles vaccines.
To memorize vaccine types in order of decreasing viral component quantity, use the mnemonic: "Live Whole Split Subunit" (Live → Whole-virion → Split/fractionated → Subunit).
Class and exam questions
What happens to the genotype upon complete loss of virulence?
Complete loss of virulence during attenuation indicates an irreversible change in the microorganism's genotype.
Why is the measles virus passaged on cell cultures?
Repeated passage allows for obtaining attenuated (weakened) non-pathogenic strains that retain immunogenicity and are suitable for the production of live vaccines.
When might vaccination prove ineffective?
When major mutational changes have occurred in the antigenic structure of the circulating virus, and a new set of antigens was not included in the preparation.
What else to study on this topic
- Anti-epidemic measures during outbreaks (isolation, mask mandates, cohort separation)
- Indications for hospitalization on epidemiological grounds
- Specific drug prophylaxis during the epidemic period (rimantadine, oseltamivir, interferons)
- Clinical criteria and diagnostic algorithm for influenza
- Epidemiology of measles: reservoir, contagious period, and transmission mechanism
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