3. 2 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 and later in the US

4. 3 The wife of the British Ambassador in Turkey, in March 1717 wrote, following the variolation of her son, to a friend in England: “The small pox, so fatal, so general amongst us, is entirely harmless here by the invention of ingrafting….I am patriot enough to bring this invention into fashion in England. The wife of the British Ambassador in Turkey, in March 1717 wrote, following the variolation of her son, to a friend in England: “The small pox, so fatal, so general amongst us, is entirely harmless here by the invention of ingrafting….I am patriot enough to bring this invention into fashion in England. Introduction of variolation

5. 4 Milestones in immunization u 1780AD u Edward Jenner discovers small pox vaccine

6. 5 Edward Jenner Discovery of small pox vaccine

7. 6 Edward Jenner Among patients awaiting small pox vaccination

8. 7 1920s Diphtheria and Tetanus 1934 Pertussis 1955 Salk polio Modern era of the vaccine 1885 Rabies vaccine (Pasteur)

9. 8 1960s Mumps measles and rubella virus Sabin polio 1990s Hepatitis and varicella 1985 Haemophilus Modern era of the vaccine  2000 Human Papillomavirus (HPV)

10. 9 Pre- & post-vaccine incidence of common preventable diseases

11. 10 Different modes of acquiring immunity Natural resistance Artificial Natural Passive Artificial Natural Active Immunity Acquired

12. 11 NaturalArtificial Colostral transfer of IgA Placental transfer of IgG Antibodies or immunoglobulins Immune cells Passive Immunity

13. 12 disease indication antibody source Passive Immunization human, horsediphtheria, tetanusprophylaxis, therapy vericella zoster human immunodeficiencies gas gangrene, botulism, snake bite, scorpion sting horse post-exposure rabies, human post-exposure hypogamma- globulinemia human prophylaxis

14. 13 Advantages Disadvantages serum sickness immediate protection no long term protection graft vs. host disease (cell graft only) risk of hepatitis and Aids Advantages and Disadvantages of Passive Immunization

15. 14 Active Immunization Natural Artificial exposure to sub- clinical infections Attenuated organisms killed organisms sub-cellular fragments toxins others

16. 15 tuberculosis not used in this country polio* not used in std. schedule measles, mumps & rubella yellow fever Military and travelers Varicella zoster children with no history of chicken pox hepatitis A standard 2006 Live Attenuated Vaccines Influenza selected age group (5-49)

17. 16 polio influenza elderly and at risk typhoid, cholera, plague epidemics and travelers rabies post exposure pertussis replaced by the acellular vaccine Killed Whole-Organism Vaccines Q fever population at risk

18. 17 Microbial Fragment Vaccines Bordetella. Pertussis virulence factor protein Haemophilus influenzae B protein conjugated polysaccharide Streptococcus pneumoniae Polysaccharide mixture Neisseria meningitidis polysaccharide

19. 18 Microbial Fragment Vaccines Clostridium tetani (tetanus) inactivated toxin (toxoid) Corynebacterium diphtheriae inactivated toxin (toxoid) Vibrio cholerae toxin subunits Hepatitis B virus cloned in yeast

20. 19 Modification of Toxin to Toxoid toxin moiety antigenic determinants chemical modification ToxinToxoid

21. 20 anti-Idiotype Vaccine Immuno-dominant peptide Future Vaccines DNA

22. 21 anti-Idiotype Vaccine

23. 22 Antiidiotype antibody in tolerance Antiidiotype antibody production Antiidiotype mediated tolerance

24. 23 Adjuvants Salts: Al(OH)3; AlPO4; CaPO4 Be(OH)2 Yes No Human useMode of action Slow release of antigen; TLR interaction and cytokine induction Adjuvant type Slow release of antigenNo Mineral oils without bacteria Yes Bacteria in Mineral oils (Mycobacteria, Nocardia) No Slow release of antigen TLR interaction and cytokine induction

25. 24 Adjuvants Human useMode of actionAdjuvant type Synthetic polymers: Liposomes ISCOM Poly-lactate Slow release of antigenNo Yes Bacteria: Bordetella pertussis Mycobacterium bovis (BCG and others) No TLR interaction and cytokine induction Bacterial products: Myramyl peptides No TLR interaction and cytokine induction

26. 25 Adjuvants Poly-nucleotides: CpG No* Human useMode of action TLR interaction and cytokine induction Adjuvant type Cytokines: IL-1, IL-2, IL-12, IFN- γ, etc. No* Activation of T and B cells and APC *Used in experimental immunotherapy of human malignancies

27. 26 Recommended Childhood Immunization Schedule MMWR, 55: Jan 5, 2007 Recommended age rangeCatch-up immunizationCertainigh risk groups

28. 27 Recommended Immunization Schedule for Ages 7-18 MMWR, 55: Jan 5, 2007 Recommended age rangeCatch-up immunizationCertainigh risk groups

29. 28 Recommended Immunization Schedule for Ages 7-18 MMWR, 55: Jan 5, 2007 Recommended age rangeCatch-up immunizationCertain high risk groups

30. 29 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 100-300 doses 1 in 1750 doses 1 in 100,000 doses 1 in 300,000 doses