Specific prophylaxis and treatment of infectious diseases Medical biology, microbiology, virology, immunology department By as. E.V. Pokryshko

Active immunization. In active immunization, the immune system is stimulated by administration of vaccines to develop a disease-specific immunity.

Vaccines are preparations of antigens whose administration artificially establishes a state of immunity without causing disease. Vaccines are designed to stimulate the normal primary immune response.

Vaccine Groups Used in Active Immunization Killed pathogens Living pathogens with reduced virulence (attenuated) Purified microbial immunogens (proteins, polysaccharides, conjugate vaccines) Toxoids Experimental vaccines

Attenuated vaccine consist of living strains of microorganisms (pathogens) with reduced virulence that do not cause disease. Advantages: optimum vaccination protection; a single application often suffices, since the microorganisms reproduce in the vaccinated person, providing very good stimulation of the immune system.

Attenuated vaccine The principle disadvantage of living attenuated vaccines is the possible reversion to virulence through mutation or recombination; do not use in immunocompromised persons and during pregnancy (some exceptions) – strains may cause disease in individuals who lack adequate immune responses, such as those with AIDS.

Pathogens can be attenuated, that is, changed into nondisease-causing strains, by various procedures, including moderate use of heat, chemicals, desiccation, and growth in tissues other than the normal host. Attenuated vaccines are used against smallpox, anthrax, rabies, tuberculosis, plague, brucellosis, tularaemia, yellow fever, influenza, typhus fever, poliomyelitis, parotitis, measles, etc.).

Killed / lnactivated Vaccines are prepared by killing or inactivating microorganisms. They cannot reproduce or replicate within the body and are not capable of causing disease (enteric fever, paratyphoid, cholera, whooping cough, poliomyelitis and leptospirosis vaccines, etc.).. When microorganisms are killed or inactivated by treatment with chemicals, radiation, or heat, the antigenic properties of the pathogen are retained. The principle disadvantage Vaccination protection often not optimum, vaccination has to be repeated several times.

Toxoids are bacterial exotoxins detoxified by formaldehyde treatment that still retain their immunogen function. These are used against tetanus, botulism, diphtheria.

Purified microbial immunogens Proteins - often recombinant antigens, i.e., genetically engineered proteins; well-known example: hepatitis B surface (HBs) antigen. Polysaccharides - Chemically purified capsular polysaccharides of pneumococci, meningococci, and Haemophilus influenzae serotype b; problem: these are T cell- independent antigens that do not stimulate antibody production in children younger than two years of age. Conjugate vaccines - Coupling of bacterial capsular polysaccharide epitopes to proteins, e.g., to tetanus toxoid, diphtheria toxoid, or proteins of the outer membranes of meningococci; children between the ages of two months and two years can also be vaccinated against polysaccharide epitopes.

Associated vaccines are used for specific prophylaxis of infectious diseases: whooping cough-diphtheria-tetanus vaccine, diphtheria- tetanus associated anatoxin, whooping cough-diphtheria. Methods of preparing associated vaccines are being devised which will provide for the production of antibacterial, antitoxic and antivirus immunity.

Experimental vaccines are DNA vaccines. Purified DNA that codes for the viral antigens (proteins) and is integrated in plasmid DNA or nonreplicating viral vector DNA. The vector must have genetic elements – for example a transcriptional promoter and RNA-processing elements – that enable expression of the insert in the cells of various tissues (epidermis, muscle cells).

Routes of Vaccination. Antigens in a vaccine may be given via a number of routes: intradermally (into the skin), subcutaneously (under the skin), intramuscularly (into a muscle), intravenously (into the bloodstream), and into the mucosal cells lining the respiratory tract through inhalation, or orally into the gastrointestinal tracts. The effectiveness of vaccines depends on how they are introduced into the body.

Passive immunization. Passive immunity can be used to prevent diseases when there is not sufficient time to develop an acquired immune response through vaccination. The passive immunity obtained by this method is limited to a few weeks (or months at most).

Passive immunization. The administration of sera, pooled gamma globulin that contains various antibodies, specific immunoglobulins, or specific antitoxins provides immediate protection. In most cases, homologous (human) hyperimmune sera (obtained from convalescent patients or patients with multiple vaccinations) are used.

The administration of antitoxins and immunoglobulins to prevent disease occurs after exposure to a toxin and/or an infectious microorganism. Antitoxins are used to neutralize the toxins. Antitoxic sera are employed for treatment and for prophylaxis of tetanus, gas gangrene and botulism. Antimicrobial sera are used against anthrax, encephalitis and influenza in the form of globulins and gamma globulins.

If an antigen is injected into an animal, the latter produces different types of antibodies against various epitopes of the antigen (antigenic determinants). Complex mixture of antibodies contains antibodies to all determinants as well as antibodies that are heterogeneous with respect to heavy chain isotype, light chain type, allotype, variable region sequence, and idiotype. The antibodies thus generated are polyclonal in nature. This means different clones of antibody secreting cells are simultaneously synthesizing the antibody. In all microbial infections, body react with polyclonal antibody production.

Monoclonal antibodies (MCA) are antibodies produced by a single clone and directed against a single antigenic determinant. MCA can be generated in the laboratory: the mouse splenic lymphocytes could be fused with mouse myeloma cells to produce hybrid cells (hybrydoma). Among the two cell types chosen for fusion, one provides the hybrid cell immortality (myeloma cell) while the other (splenic plasma cell) provides the antibody producing capacity.

Production of the monoclonal antibodies

Monoclonal antibodies Monoclonal antibodies are being used widely as research tools to study protein structure and virus and toxin neutralization, and to isolate specific proteins from complex mixtures. Moreover, many commercially available monoclonal Abs are being used in extremely sensitive and specific techniques for the diagnosis of various diseases (ELISA, IFT) and, as mentioned earlier, for the experimental treatment of several human diseases.