Molecular and synthetic vaccines

Methods for producing molecular vaccines

Molecular vaccines are based on the use of purified antigens—molecules or small fragments thereof that are recognized by our immune system. Since the preparation contains no whole pathogens, such vaccines are considered maximally safe and precisely targeted.

There are three main methods for obtaining the required protective antigen:

• Biological synthesis. The target molecules are isolated from cultures of natural bacteria or viruses directly during their cultivation.
• Genetic engineering (recombinant technologies). The pathogen's gene is inserted into the genome of harmless microbes, forcing them to synthesize a foreign antigen. A classic clinical example is the hepatitis B vaccine, where the protective antigen is produced by a recombinant strain of common yeast. This method is also actively used to develop preparations against HIV, malaria, syphilis, and influenza.
• Chemical synthesis. Artificial reconstruction of the antigen determinant "in vitro" after full decoding of its chemical structure.

Toxoids as a classical example

An important group of molecular vaccines is toxoids. They build immunity not against the microbe itself, but against the toxin it produces. Mass immunization with diphtheria and tetanus toxoids has dramatically reduced morbidity and eliminated epidemics. There are also preparations against botulism, gas gangrene (caused by Cl. perfringens and Cl. novyi), cholera, and staphylococcal infections.

Their production technology is strictly regulated and includes several stages:

1. Cultivation: large-scale cultivation of bacteria for exotoxin production.
2. Inactivation: the exotoxin is treated with a 0.4% formaldehyde solution and kept warm (37 °C) for 3–4 weeks. The molecule completely loses its toxicity while retaining its specific antigenicity.
3. Purification and concentration: removal of ballast microbial metabolic products and remnants of the nutrient medium.
4. Sorption (addition of an adjuvant): to enhance immunogenicity, sorbents (aluminum hydroxide gel or aluminum phosphate) are added to the preparation.

Finished toxoids are administered subcutaneously or intramuscularly. Their dosage is measured in special units: IU (antitoxin-binding units) or Lf (flocculation units).

Synthetic vaccines: solving the problem of low immunogenicity

The main problem with isolated molecules (or epitopes) is their extremely low immunogenicity. Upon entering the body, they fail to elicit a full-fledged immune response for two reasons:

• They are rapidly degraded by tissue enzymes.
• Their low molecular weight prevents them from fully attaching (adhering) to the receptors of immunocompetent cells.

To transform a weak molecular stimulus into a potent synthetic vaccine, researchers artificially enlarge the antigen. To do this, the antigenic determinant is chemically or physically/chemically "conjugated" to a high-molecular-weight carrier—a safe polymer (e.g., polyvinylpyrrolidone). In such a design, the polymer performs two functions simultaneously: it acts as a transporter ("schlapper") and as an adjuvant.

Such modification provides powerful immunological advantages:

• Transforms T-dependent antigens into T-independent ones.
• Ensures prolonged circulation of the preparation in the body.
• Significantly facilitates the adhesion of molecules by immune cells.

Note: In the Russian Federation, the development of such vaccines is actively pursued by the school of R.V. Petrov and R.M. Khaitov, an example being the influenza vaccine based on the polymer polyoxidonium.

Associated (multicomponent) vaccines

To optimize the immunization schedule, reduce the number of injections, and minimize doctor visits during mass prophylaxis, associated vaccines are created. These are preparations containing several distinct antigens simultaneously (including live or inactivated components). The human immune system is physiologically capable of reacting to dozens of antigens at once without overload, yet the primary technological challenge is achieving a perfectly balanced composition to prevent antigen competition and excessive reactions.

Depending on the nature of the constituent antigens, two types of such vaccines are distinguished:

• Polyvalent vaccines. Contain homogeneous antigens (different types or strains of the same pathogen). For example, oral polio vaccine (types I, II, and III viruses) or polytoxoid (a mixture of toxoids against botulism, tetanus, and gas gangrene).
• Combined vaccines. Consist of heterogeneous antigens directed against completely different diseases. A classic example is the DTP vaccine, containing the whole-cell pertussis component along with tetanus and diphtheria toxoids, as well as the MMR vaccine (measles, mumps, and rubella).

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Units of toxoid dosage (Lf and IU) and their biological significance in immunology
• Mechanisms of transforming T-dependent antigens into T-independent ones using polymer carriers
• The role of aluminum hydroxide and aluminum phosphate in forming an antigen depot
• Principles of preventing antigenic competition in combined vaccines
• Stages of creating recombinant vaccines using the hepatitis B vaccine as an example

Other topics in the «Immunoprophylaxis Agents» section

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