Immunoprophylaxis (prophylactic immunization) Immunoprophylaxis • Types of immunization • Immunoglobulins and vaccines • Strategies in vaccine preparation • Mechanisms of action of different types of vaccines NATURAL Transplacental transfer of IgG Immunity after infection PASSIVE ACTIVE Immunoglobulines in milk (breast feeding) IMMUNIZATION Immunoglobulins and antisera (antitoxins) Vaccination ARTIFICIAL (PROPHYLACTIC) Pasive immunization (Administration of immunoglobulins/antisera) For prophylaxis or therapy immediate effect temporary immunity (weeks, months) Antibodies-Immunoglobulins (Ig) Human immunoglobulins (from blood donors) - human serum (gama)globulin (Ig of various specificity) e.g. for immunodeficiencies... - specific immune globulins (high-titre of specific Ig) e.g. for hepatitis B, tetanus, rabies... Animal (horse) sera (antisera, antitoxins) e.g. for snake venoms, botulism, diphteria... serum disease!!! Active immunization (Vaccination) Primarily for prophylaxis Requires time (weeks) for induction of immune response Administration - prior to exposure to pathogen (exception: rabies vaccine) - post-exposure (in combination with specific Ig) Adjuvant - increases immunogenicity Long-lasting immunity - multiple doses needed for most vaccines Herd immunity Vaccine types Live (attenuated) vaccines - contain live, attenuated (weakend) infectious agents Inactivated (killed) vaccines - contain killed whole infectious agents Subunit (antigenic) vaccines - contain structural parts/products of infectious agents obtained from pathogens by isolation and purification synthetic (genetic engineering) Conjugate vaccines - contain T-independent antigen bound to T-dependent antigen Combined (polyvalent) vaccines - contain several antigens of one or more different pathogens New approches for vaccines Live (attenuated) vaccines Principle Imunization with attenuated (weakened) pathogen Examples Several viral vaccines (against polio (oral-Sabin), mumps, measles, rubella, varicella) and some bacterial (BCG for tuberculosis)... Advantages Induction of both humoral (Abs) and cellular response (CTLs) Long-lasting immunity (administered in one or two doses) Limitations Risk in immunocompromised persons Instability (termolabile) BCG (limited efficacy) Inactivated (killed) vaccines Principle Imunization with killed (inactivated) whole infective agents Examples Vaccines against pertussis, typhoid, polio (Salk), influenza... Advantages Greater stability Safety (no risk of infection) Limitations Low immunogenicity (only Ab induced, adjuvant required) Shorter immunity (multiple, booster administration required) Subunit (antigenic) vaccines Principle Immunization with structural antigens (protein or polysaccharide) of pathogens or their products (e.g. toxoid) Examples Vaccine against pertussis (acellular), tetanus and diphteria (toxoid), influenza (Hemagglutinin and Neuraminidase), hepatitis B (HBsAg) and human papilloma virus (L1 protein) – so-called virus-like particles (VLP), pneumococcal and meningococcal polysaccharide vaccines... Advantages Same as for inactivated vaccines (greater safety) Limitations Same as for inactivated vaccines (lower immunogenecity) Conjugate vaccines Principle Immunization with capsular polysaccharide antigen of one pathogen (weak immunogen in children) conjugated to protein antigen of another pathogen (strong immunogen) Principle of immunization with conjugated vaccines Principle of immunization with conjugated vaccines Principle of immunization with conjugated vaccines Principle of immunization with conjugated vaccines Conjugate vaccines Principle Immunization with capsular polysaccharide antigen of one pathogen (weak immunogen in children) conjugated to protein antigen of another pathogen (strong immunogen) Example Vaccines against pneumococcus, menigococcus and H. influenzae type B (capsular polysaccharide bound to diptheria toxoid ) Advantages Same as for subunit vaccines Good immune response to capsular antigens Efficient in children in the first two years of life and asplenic persons Limitations Same as for subunit vaccines Relatively high cost Combined (polyvalent) vaccines Principle Simultaneous immunization with several serotypes of one pathogen (either attenuated strains or antigens) or several different pathogens Examples Vaccines against tetanus, diphtera and pertussis (DTP), measles, mumps and rubella (MMR), polysaccharide or conjugate pneumococcal vaccines... Advantages The same as for appropriate single vaccines Good immune response to every component in vaccine Practical (fewer administration, fewer visits of doctor...) Limitations Same as for single vaccines New approaches for vaccines (Hybride vaccines with live viral vectors) Principle Immunization with live viral vectors (e.g. vaccinia virus) with introduced genes for immunodominant peptides of different pathogens Examples Ongoing clinical trials for several vaccines (e.g. against HIV) Advantages Induction of both humoral (Abs) and cellular immune response (CTLs) Possibility of polyvalent vaccine preparation Limitations Repeated administration not possible New approaches for vaccines (DNA vaccines) Principle Injection of bacterial plasmid with DNA containing genes for various microbial antigenes Example Ongoing clinical trials for several pathogens Advantages Induction of both humoral (Abs) and cellular immune response (CTLs) Simple handling, possibility of polyvalent vaccines preparation Limitations Mechanism of action and possible adverse effects not well understood 1. Example of artificial active immunization is a. antigens from different infectious agents 2. Example of artificial passive immunization is b. immunity to tetanus after injection of tetanus toxoid 3. Example of natural active immunization is c. immunity to tetanus after injection of antitetanus immunoglobulins 4. Example of natural passive immunization is d. whole killed microorganisms 5. Live attenuated vaccine against polio e. induce production of mucosal IgA f. parts of infective agents or their products 6. Subunit vaccines contain g. high-affinity antibodies to polysaccharides 7. Inactivated vaccines contain 8. Combined vaccines contain h. immunity after recovery from infectious disease 9. Conjugate vaccines induce production of 10. Adjuvants increase b 1.____ c 2.____ h 3.____ i. immunogenicity of antigens in vaccines j. transplacental transfer of IgG j 4.____ e 5.____ f 6.____ d 7.____ a 8.____ g 9.____ h 10.___