Typhoid Vaccine

Serological classification of Salmonella

Typhoid fever pathogens belong to Salmonella, which possess a very extensive antigenic structure. Representatives of the first five groups are most frequently encountered: A, B, C, D and E. If the isolated bacterium reacts with group-specific serum, this confirms that it belongs to Salmonella.

Pathogen identification is carried out in two stages:

1. Group determination using the O-antigen (somatic). Its receptors are designated by numbers. There are common receptors for different groups (e.g., 1 and 12) and strictly specific ones. Thus, a reaction with O-serum containing receptor 9 indicates group D, while reaction with receptor 4 indicates group B.
2. Species determination using the H-antigen (flagellar). For this purpose, first-phase sera are used, which are type-specific (species-specific). For example, Hm serum is used in group D, and Hi serum in group B. If the first phase is insufficient for precise identification, second-phase sera, which have a group-specific character, are used.

Diagnostics and antibody detection

To confirm the diagnosis or assess a patient's immunity, antibodies against the bacteria are sought rather than the bacteria themselves. For this purpose, the passive hemagglutination test with erythrocyte diagnostic agents is used—preparations where a specific antigen is fixed onto erythrocytes.

Note: The presence of antibodies to the Vi-antigen does not always indicate a current infection; they may be present in the blood of individuals who have previously received the vaccine.

Classical vaccines

Historically, the first preparations for the prevention of typhoid fever were inactivated vaccines, proposed by R. Pfeiffer and W. Kolle at the end of the 19th century.

Their main advantage is their fundamental inability to cause infectious complications. However, due to the presence of impurities, they can be toxic and allergenic. The main rule in their creation is that the method of pathogen inactivation must not destroy protective antigens. A significant drawback of such vaccines is that they are less effective than live attenuated preparations, since dead microbial cells are incapable of self-maintenance and replication within the body.

Modern generations of vaccines

The desire to reduce toxicity and increase efficacy has led to the development of new types of vaccines:

• Subunit vaccines: created by fractionating inactivated microorganisms. Only purified protective antigens are included in the final preparation.
• Chemical vaccines: represent the next stage of evolution. Active molecules are isolated in pure form or chemically synthesized.
• Genetically engineered vaccines: virulence genes are excluded from the pathogen's genome, and genes encoding protective antigens are inserted into a vector. The vaccinia virus is often used as it excellently stimulates humoral and cellular immunity on its own.
• New-type synthetic vaccines: constructed from entirely artificial subunits. They contain B-cell epitopes (peptides or polysaccharides), T-cell epitopes, and innate immunity activators. Despite their rational design, they currently exhibit weaker immunogenicity due to incomplete modern knowledge regarding the nature of antigenicity.

Toxoids and combination preparations

The use of whole microbial toxins for immunization is impossible due to their danger. Therefore, toxoids are used—toxins inactivated by formalin or other agents. They lose toxicity while completely retaining antigenicity.

Often, antigens of different pathogens and toxoids are combined into combination vaccines. Such mixing can produce an adjuvant effect—a mutual enhancement of the immune response to individual components. A classic example of such a preparation is the DTP vaccine, which contains diphtheria and tetanus toxoids along with killed Bordetella pertussis bacteria.

Class and exam questions

What else to study on this topic

• Structural features of the O-antigen and the distribution of common receptors among Salmonella groups.
• The two-phase nature of the H-antigen and the algorithm for using second-phase sera.
• The mechanism of the passive hemagglutination test and the principle of antigen fixation on erythrocytes.
• The adjuvant effect: how components of combination vaccines enhance each other's action.
• The use of the vaccinia virus as a vector for genetically engineered preparations.

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.