2 QUESTIONS OF LECTURE n History of immunization n Passive immunization n Hypersensitivity reactions by injection of the serum n Monoclonal antibodies n Immunoprophylaxis. Active immunization n Adjuvants. Mechanism of action of vaccines

3 Milestones in immunization u 1500BC u Turks introduce variolation u 3000BC u Evidence of sniffing powdered small pox crust in Egypt u 2000BC u Sniffing of small pox crust in China u 1700AD u Introduction of variolation in England

4 Edward Jenner Discovery of small pox vaccine (1780) Jenner replaced variolation by vaccination (global eradication of the smallpox)

5 Edward Jenner Among patients awaiting small pox vaccination

6 1920s Diphtheria and Tetanus 1934 Pertussis 1955 Salk polio Modern era of the vaccine 1885 Rabies vaccine (Pasteur)

7 1960s Mumps, measles and rubella virus Sabin polio 1990s Hepatitis and varicella 1985 Haemophilus Modern era of the vaccine

8 Pre- & post-vaccine incidence of common preventable diseases

9 Different modes of acquiring immunity Natural resistance Artificial Natural Passive Artificial Natural Active Immunity Acquired

10 Natura l Artificia l Colostral transfer of IgA Placental transfer of IgG Antibodies or immunoglobulins Immune cells Passive Immunity

11 disease indication antibody source Passive Immunization human, horsediphtheria, tetanusprophylaxis, therapy varicella-zoster human immunodeficiencies gas gangrene, botulism, snake bite, scorpion sting horse post-exposure rabies human post-exposure hypogamma- globulinemia human prophylaxis

12 Advantages Disadvantages serum sickness or anaphylaxis immediate protection no long term protection risk of hepatitis and AIDS Advantages and Disadvantages of Passive Immunization

13 Hypersensitivity reactions by injection of the serum n Anaphylactic shock n Anaphylaxis (Gk. ana - away from, back from; phylaxis - protection). Anaphylaxis is a form of altered reactivity, a state of the organism’s increased sensitivity induced by repeated injection of foreign proteins. n Serum Sickness n 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

14 MONOCLONAL ANTIBODIES n A single antibody forming cell or clone produces antibodies specifically directed against a single antigen or antigenic determinant only. Such antibodies produced by a single clone and directed against a single antigenic determinant are called monoclonal antibodies (MA).

15 Monoclonal Antibodies ANTIGEN MYELOMA CELLS

16 Active Immunization Natural Artificial exposure to sub- clinical infections attenuated organisms killed organisms sub-cellular fragments toxins others

17 Live Attenuated Vaccines n Live vaccines are used against a number of viral infections and some bacterial diseases. While live vaccines normally produce only self-limiting non- clinical infections and subsequent immunity, they carry a serious risk of causing overt disease in immunocompromised individuals.

18 tuberculosis polio* measles, mumps & rubella yellow fever Military and travelers varicella zoster children with no history of chicken pox hepatitis A not required in SC Live Attenuated Vaccines

19 Killed Whole-Organism Vaccines n Killed (heat, chemical or UV irradiation) viral vaccines include those for polio (Salk vaccine), influenza, rabies, influenza, rabies, etc. Most bacterial vaccines are killed organisms (typhoid, cholera, plague, pertussis, etc.). Killed vaccines, as usually, are reactogenic and vaccines of limited effectiveness.

20 influenza elderly and at risk typhoid, cholera, plague epidemics and travelers rabies post exposure pertussis Killed Whole-Organism Vaccines Q fever population at risk

21 Microbial Fragment Vaccines Bordetella pertussis virulence factor protein Haemophilus influenzae B protein conjugated polysaccharide Streptococcus pneumoniae polysaccharide mixture Neisseria meningitidis polysaccharide

22 Microbial Fragment Vaccines Clostridium tetani (tetanus) inactivated toxin (toxoid) Corynebacterium diphtheriae inactivated toxin (toxoid) Vibrio cholerae toxin subunits Hepatitis B virus cloned in yeast

23 Toxoids n Toxoids are inactivated toxins that have lost their active site but have maintained their immunogenic determinants. Administration of the toxoid induces the production of antibodies capable of neutralizing the toxins by blocking their adsorption to cellular receptors.

24 Modification of Toxin to Toxoid toxin moiety antigenic determinants chemical modification ToxinToxoid

25 anti-Idiotype Vaccine Immuno-dominant peptide Future Vaccines DNA

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28 Recommended Childhood Immunization Schedule

29 Vaccines n The protective immunity conferred by a vaccine may be lifelong (measles, mumps, rubella, etc.) or may last as little as six months (cholera) n Vaccines can be used as immunotherapeutic agents. The use of vaccines to stimulate the immune system as therapy for chronic or latent infections (herpes, leprosy, tuberculosis)

30 Active immunization may cause n fever, malaise and discomfort n joint pains or arthritis (rubella) n convulsions, sometimes fatal (pertussis) n neurological disorders (influenza) n allergies to eggs may develop as a consequence of viral vaccines produced in eggs (measles, mumps, influenza, yellow fever).

31 Adverse Events Occurring Within 48 Hours DTP of Vaccination Event Frequency local redness, swelling, pain 1 in 2-3 doses systemic: mild/moderate fever, drowsiness, fretfulness vomiting anorexia 1 in 2-3 doses 1 in 5-15 doses systemic: more serious persistent crying, fever collapse, convulsions acute encephalopathy permanent neurological deficit 1 in doses 1 in 1750 doses 1 in 100,000 doses 1 in 300,000 doses

32 ADJUVANTS n Adjuvant is a substance which enhances antigenic efficiency of vaccines. Adjuvant maintains the antigen in close proximity to immune cells and for keep the antigen from dissipating from the inoculation site.

33 TYPES OF ADJUVANTS n Alum (aluminum hydroxide gels, which keep the antigen from dissolving away) n microorganisms (e.g. whole B. pertussis) n Freund’s incomplete (antigen in an emulsion of mineral oil and water) n Freund’s complete (complete because it adds mycobacterial antigens to the emulsion) n Liposomes

34 Mechanism of action of vaccines n First, the lag or latent period is shorter n Second, the ultimate level of antibody is higher and persists longer than in the primary response n Third, there is more IgG than IgM in the antibody produced has occurred n Fourth, the amount of antigen is smaller than for the primary response n Finally, the antibody produced has a higher mean affinity in the secondary response

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