Molecular and Synthetic Vaccines

Methods of Obtaining Molecular Vaccines

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

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

• Biological synthesis. The target molecules are isolated from natural bacterial or viral cultures directly during their cultivation.
• Genetic engineering (recombinant technologies). The pathogen gene is inserted into the genome of safe 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 ordinary yeast. This method is also actively used to develop preparations against HIV, malaria, syphilis, and influenza.
• Chemical synthesis. Artificial recreation of the antigenic determinant "in vitro" after complete decoding of its chemical structure.

Toxoids as a Classical Example

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

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 microbial metabolic byproduct waste and residual nutrient media.
4. Sorption (adjuvant addition): 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 specific units: IU (antitoxin binding units) or Lf (flocculation units).

Synthetic Vaccines: Solving 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 properly attaching (adhering) to the receptors of immunocompetent cells.

To transform a weak molecular stimulus into a strong synthetic vaccine, researchers artificially enlarge the antigen. For this purpose, the antigenic determinant is chemically or physico-chemically "conjugated" to a high-molecular-weight carrier—a safe polymer (e.g., polyvinylpyrrolidone). In such a design, the polymer performs dual functions: it works as a transporter ("schlapper") and as an adjuvant.

This modification provides powerful immunological advantages:

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

Note: Development of such polymer-based influenza vaccines has been pioneered by modern immunopharmacology schools utilizing soluble macromolecular carriers.

Associated (Multicomponent) Vaccines

To optimize immunization schedules, reduce the number of injections, and minimize physician visits during mass prophylaxis, associated vaccines are created. These are preparations that include several different antigens simultaneously (including live or inactivated components). The human immune system is physiologically capable of responding to dozens of antigens at once without overload; however, the primary technological challenge is achieving an ideal compositional balance to eliminate antigenic 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, the oral polio vaccine (poliovirus types I, II, and III) or polytoxoids (a mixture of toxoids against botulism, tetanus, and gas gangrene).
• Combination vaccines. Consist of heterogeneous antigens directed against completely different diseases. A classic example is the DTaP (or DTP) vaccine, containing a whole-cell pertussis component along with tetanus and diphtheria toxoids, as well as the MMR vaccine (measles, mumps, and rubella).