Immunotherapy and Prevention

1. Sumy State University The Department of Infectious Diseases andEpidemiology with Course of Microbiology, Virology and Immunology Immunotherapy and Prevention Tatyana Ivakhnyuk 2011

2. Active Immunization Stimulates the host’s immune system to produce specific antibodies or cellular immune responses or both which would protect against or eliminate a disease.

3. Passive Immunization A preparation of antibodies that neutralizes a pathogen and is administered before or around the time of known or potential exposure.

4. Vaccines Provide an antigenic stimulus that does not cause disease but can produce long lasting, protective immunity

5. Sterile protection Non sterile protection Specific Specific Quick amplification Pathogen neutralization Specific Clearance of the pathogen before spreading Clearance of the pathogen after infection Extra cellular pathogens or free intracellular pathogens Antibody mediated Intracellular pathogen with cell to cell transmission Cell mediated Principles and Effects of Vaccination

6. Types of Vaccines and Their Characteristics

7. Vaccine technologies • Examples • Live vaccines polio, yellow fever • Recombinant vaccines RSV • Killed vaccines influenza, pertussis • Plasma derived vaccines Hepatitis B • Polysaccharide conjugates Hib, Pneumo • Peptide vaccines Malaria • Subunit vaccines HIV candidates • DNA vaccines Influenza • Combination vaccines DPT • Passive (antibodies) e.g. HBIG, VZIG

8. Types of Vaccines and Their Characteristics • Attenuated whole-agent vaccines use living but attenuated (weakened) microbes. Live vaccines more closely mimic an actual infection. Lifelong immunity, especially with viruses, is often achieved without booster immunizations, and an effectiveness rate of95% is not unusual. This long-term effectiveness probably occurs because the attenuated viruses replicate in the body, increasing the original dose and acting as a series of secondary (booster) immunizations.

9. Attenuated whole-agent vaccines

10. Ideal properties of a live vaccine Attenuated microorganism which replicates in the host thus eliciting immune responses similar to natural infection Able to elicit lifelong protection using only one or two doses Disease causing capacity is virtually eliminated. Elicits both humoral and cellular immunity

11. Examples of Attenuated or live vaccines Live attenuated vaccines oral polio, yellow fever mumps, measles, VZV tuberculosis (BCG)

12. Types of Vaccines and Their Characteristics Inactivated whole-agent vaccines use microbes that have been killed, usually by formalin or phenol. Inactivated virus vaccines used in humans include those against rabies (animals sometimes receive a live vaccine considered too hazardous for humans), influenza, and polio (the Salk poliovaccine). Inactivated bacterial vaccines include those for pneumococcal pneumonia and cholera. Several long-used inactivated vaccines that are being replaced for most uses by newer, more effective types are those for pertussis (whooping cough) and typhoid.

13. Inactivated whole-agent vaccines

14. Types of Vaccines and Their Characteristics • Toxoids, which are inactivated toxins, are vaccines directed at the toxins produced by a pathogen. The tetanus and diphtheria toxoids have long been part of the standard childhood immunization series. They require a series of injections for full immunity, followed by boosters every 10 years. Many older adults have not received boosters; they are likely to have low levels of protection.

15. Tetanus Toxoid chemical and temperature modification toxin moiety antigenic determinants Modification of Toxin to Toxoid (example) Extracellular Toxin of Clostridiun tetani Toxin

16. Types of Vaccines and Their Characteristics Subunit vaccines use only those antigenic fragments of a microorganism that best stimulate an immune response. Subunit vaccines that are produced by genetic modification techniques, meaning that other microbes are programmed to produce the desired antigenic fraction, are called recombinant vaccines. For example, the vaccine against the hepatitis B virus consists of a portion of the viral protein coat that is produced by a genetically modified yeast.

18. Types of Vaccines and Their Characteristics Conjugated vaccines have been developed in recent years to deal with the poor immune response of children to vaccines based on capsular polysaccharides.

19. Polysaccharide vaccines Unique type of inactivated subunit vaccine composed of long chains of sugar molecules that make up the surface capsule of certain bacteria. Available for Pneumococcal disease, meningococcal disease and Haemophilus influenzae type b

20. Combination vaccines Examples influenza trivalent OPV, inactivated IPV DPT, DPT/Hib, etc. MMR, MMRV PnC/MnC Advantages: only one needle at a visit may reduce number of visits reduces costs of administration geographic tailoring Disadvantages: loss of immunogenicity due to competition technically more difficult to produce higher production costs higher evaluation costs

21. Humoral component Tetanus Dyphteria H. influenzae Influenza Measles Varicella (herpes zoster) Dengue S. pneumoniae Cellular components BCG HIV Herpes type 1&2 Shingles (herpes zoster) Influenza in elderly Varicella (herpes zoster) Measles Correlates ?

22. Description of immunity Postinfection Postvaccine Active Passive Humoral Cellular Antibacterial Antiviruses Antitoxins Antifungal Specific Nonspecific Group specific, species specific, Type-specific

23. BCG (bacillus Calmette-Guerin) • Content:– living or attenuated, liophilic dried up culture unpathogenic strain of M. tuberculosis, was found by the French scientists Calmette and Guerin. Used for the active specific prophylaxis of tuberculosis. Plugged in the calendar of inoculations. Contra-indicated people with violation of cellular link of immunity. Whattypeofimmunity (originally) iscreatedinanorganismafterintroduction? Postvaccine Active Cellular Antibacterial General Specific

24. Killed brucellosis vaccine • Content:– It contains the killed by heat the cow-type and sheep-type species of the brucella. It is using for immunotherapy by chronic brucellosis. It has high sensibillization and allergic ability and it is using only for patients with normegric reaction of the organism on the intra-skin injection of the brucellin. For the patients with hyperergia and allergic reaction and for person with generalized infection the vaccination is dangerous. The intra-skin therapy is making often then intravenous. The injection of the brucellin is useful for same patients. Whattypeofimmunity (originally) iscreatedinanorganismafterintroduction? Postvaccine Active Cellular Antibacterial General Specific

25. Meningococcal chemical vaccine Content:This vaccine contains cleared polysaccharide of Neisseriameningitidis group A and C. Appointment: Prophylaxis of cerebrospinal meningitis, caused meningococcus of serogroupp A and C. Vaccination is recommended in endemic regions, and also in the case of epidemic, caused meningococcus of serogorupp A or C. Whattypeofimmunity (originally) iscreatedinanorganismafterintroduction? Postvaccine Active Humoral Antibacterial General Specific

26. Staphylococcal toxoid Content: this vaccine, in which contains inactivated, which help formalin (0,4%) and temperature (56°C) exotoxinS.aureus. It is used for specific preventive and treatment of staphylococcal infections Whattypeofimmunity (originally) iscreatedinanorganismafterintroduction? Postvaccine Active Humoral Antitoxic General Specific

27. APDT Content:- аdsorbed on the hydrate of oxide of aluminium mixed vaccine, consisting of the killed microorganisms – the whooping-cough bacteria’s and toxoids – diphtherial and tetanic. Used for plannad prophylaxis. Whattypeofimmunity (originally) iscreatedinanorganismafterintroduction? Postvaccine Active Humoral Antitoxic Antibacterial General Specific

28. Adjuvant activity • Formation of a depot of antigen primarily at the • site of application from which the antigen is • released during a variable period • Increased uptake of antigen into APCs • Induction of synthesis and secretion of • enhancing factors, such as cytokines.

29. Adjuvant activity • Facilitation of antigen transport, uptake and presentation by antigen-capturing and processing cells • Repeated or prolonged release of antigen (depot effect) • Signaling of receptors activating innate immune cells to release cytokines which upregulate co-stimulatory molecules • ‘Danger signals’ from stressed or damaged tissues activate APCs • Signaling by recombinant cytokines or co-stimulatory molecules mimics classical adjuvant activity

30. Immunotherapy – preformed Ab Immune serum globulin– (gamma- globulin) contains immunoglobulin extracted from the pooled blood of at least 1,000 human donors • Treatment of choice for preventing measles, hepatitis A and replacing Ab in the immune deficient • Lasts 2-3 months

31. Immunotherapy – preformed Ab Specific immune globulin- prepared from convalescent patients in a hyperimmune state • Contains high titer of specific Ab • pertussis, tetanus, chickenpox, hepatitis B • sera produced in horses are available for diphtheria, botulism, spider and snake bites • act immediately and can protect patients for whom no other useful medication exists

32. Cell Effectors functions of antibodies prevent contacts with host cell • Neutralization • Complement mediated lyses reduce the pathogen load Inhibit bacterial toxins inhibits the pathogen penetration of the host cell • Complement binding è pathogen destruction

33. Antianthracis gamma-globulin • Content:preparation contains antitoxins. It is gamma-globulins fraction of serum of the hyperimmunized animals. There is the diminished amount of ballast matters in such preparation, that diminishes probability of development of by-reactions, above all things allergic substantially Whattypeofimmunity (originally) iscreatedinanorganismafterintroduction? Passive Humoral Antibacterial General Specific

34. Antidiphtherial antitoxic serum • Content:preparation is got by hyperimmunization of horse a diphtherialtoxoid. Effective mean of specific therapy of diphtheria. At the use it should be remembered rules of introduction of heterogenic serum, to eliminate development of anaphylactic shock and serum illness. Whattypeofimmunity (originally) iscreatedinanorganismafterintroduction? Passive Humoral Antibacterial General Specific

35. Sources of Passive Immunity • Almost all blood or blood products • Homologous pooled human antibody (immune globulin) • Homologous human hyperimmune globulin • Heterologous hyperimmune serum (antitoxin)

36. Classification the serum preparations • homogeneous serum: serum obtained from blood donor volunteers, have been immunized. • heterogeneous serum: serum obtained from blood of animals hyperimmunized.

37. Hypersensitivity reactionsby injection of the heterogeneous serum • Anaphylactic shock Type I, or anaphylactic, react ions often occur within 2 to 30 minutes after a person sensitized to an antigen is reexposed to that antigen. Anaphylaxis means opposite of protected," from the prefix ana-, meaning against, and the Greek phylaxis, meaning protection. Anaphylaxis is an inclusive term for the reactions caused when certain antigens combine with IgE antibodies. Anaphylactic responses can be systemic reactions, which produce shock and breathing difficulties and are sometimes fatal, or localized reactions, which include common allergic conditions such as hay fever, asthma, and hives (slightly raised, often itchy and reddened areas of the skin). • Serum Sickness This is a systemic form of hypersensitivity of immediate reaction. It appears 7 to 12 days following single injection of high concentration of foreign serum

38. The mechanism of anaphylaxis IgE antibodies, produced in response to an antigen (heterogenic antibody), coat mast cells and basophils. When an antigen bridges the gap between two adjacent antibody molecules of the same specificity, the cell under goes degranulation and releases histamine and other mediators.

39. Bezredka method • Bezredka method (A.M. Bezredka, a microbiologist, was born in Russia, worked in France, 1870-1940) - a specific method of desensitization of the body that is used to prevent complications after the administration of heterogeneous serums.

40. Bezredka method Heterologous hyperimmune sera (eg, antibotulinum, antitetanus, etc.) are highly concentrated; for desensitization recommended minimum dose. While under the influence of serum antigen occurs, neutralizing antibodies, fixed on the cell surface, and a decline in blood concentrations of physiologically active substances (histamine, etc.) that prevents the development of complications after re-introduction of the antigen.

41. Thank you for your attention!