1. Julio A. Ramirez, MD, FACP Professor of Medicine Chief, Infectious Diseases University of Louisville Chief, Infectious Diseases Veterans Affairs Medical Center Louisville, Kentucky, USA Vaccines in Pulmonary Medicine

2. 1 2 3 Introduction to Vaccines Vaccine Immunology Current Adult Vaccines

3. Viral & Bacterial Pathogens Introduction to Vaccines 1. Influenza Virus 2. Varicella-Zoster Virus 3. Human Papillomavirus 4. Measles Virus 5. Mumps Virus 6. Rubella Virus 7. Hepatitis A Virus 8. Hepatitis B Virus 4. N. meningitidis 1. C. tetani 2. C. diphtheriae 3. B. pertussis 5. H. influenzae 6. S. pneumoniae 7. M. tuberculosis 8. S. typhi

4. Viral & Bacterial Pathogens Introduction to Vaccines 1. Influenza Virus 2. Varicella-Zoster Virus 3. Human Papillomavirus 4. Measles Virus 5. Mumps Virus 6. Rubella Virus 7. Hepatitis A Virus 8. Hepatitis B Virus 4. N. meningitidis 1. C. tetani 2. C. diphtheriae 3. B. pertussis 5. H. influenzae 6. S. pneumoniae 7. M. tuberculosis 8. S. typhi Variola Virus: Smallpox 1796

5. Viral & Bacterial Pathogens Introduction to Vaccines 1. Influenza Virus 2. Varicella-Zoster Virus 3. Human Papillomavirus 4. Measles Virus 5. Mumps Virus 6. Rubella Virus 7. Hepatitis A Virus 8. Hepatitis B Virus 4. N. meningitidis 1. C. tetani 2. C. diphtheriae 3. B. pertussis 5. H. influenzae 6. S. pneumoniae 7. M. tuberculosis 8. S. typhi Variola Virus: Smallpox 1796

6. Smallpox (Variola Virus) Introduction to Vaccines Smallpox Variola Virus Mortality 30 to 40% Inhalation Human Disease

7. Smallpox (Variola Virus) 1980 Introduction to Vaccines Smallpox Variola Virus Mortality 30 to 40% Inhalation Human Disease

8. Smallpox Smallpox Variola Virus Mortality 30 to 40% Inhalation Smallpox Variola Virus Mortality 1 to 2% Inoculation Human Disease Introduction to Vaccines

9. Cow Disease Cowpox Virus Human Cowpox Introduction to Vaccines Smallpox: E. Jenner 1796 Smallpox Variola Virus Mortality 30 to 40% Inhalation Human Disease

10. No Smallpox Variola Virus Inhalation Human Disease Cow Disease Cowpox Virus Human Cowpox Vaccination Introduction to Vaccines Smallpox: E. Jenner 1796 Smallpox Variola Virus Mortality 30 to 40% Inhalation Human Disease

11. No Smallpox Variola Virus Inhalation Human Disease Cow Disease Cowpox Virus Human Cowpox Vaccination Introduction to Vaccines Smallpox: E. Jenner 1796 Smallpox Variola Virus Mortality 30 to 40% Inhalation Human Disease Cow Disease Cowpox Virus Latin for Cow: Vacca English: Vaccine Spanish: Vacuna

12. InoculationVaccination Introduction to Vaccines Smallpox: E. Jenner 1796

13. Tuberculosis No TB M tuberculosis Inhalation Human Disease Introduction to Vaccines

14. Tuberculosis No TB M tuberculosis Inhalation Human Disease Cow Disease M bovis Introduction to Vaccines

15. Tuberculosis More TB M tuberculosis Inhalation Human Disease Cow Disease Vaccination M bovis Introduction to Vaccines

16. Human with ID Vaccination Introduction to Vaccines Inactivation Isolation Pathogen HumanwithoutID Tuberculosis

17. Human with ID Vaccination Introduction to Vaccines Inactivation Isolation Pathogen HumanwithoutID Bacillus Calmette Guerin BCG Vaccine M. bovis Since 1921 3 billion Tuberculosis

18. Latent Infection 20% Protection Active Disease “Pulmonary TB” Active Disease “Pulmonary TB” 50% Protection Active Disease “TB Meningitis” Active Disease “TB Meningitis” 75% Protection Active Disease “Death due to TB” Active Disease “Death due to TB” 85% Protection “Outcome” “Efficacy” Introduction to Vaccines TB Vaccine Efficacy: Outcome Variable

19. Introduction to Vaccines TB Vaccine Protection for 10 to 15 years Partial Protection 50 to 60 years Prior exposure to mycobacteria may limit BCG replication (efficacy) No booster effect Childhood BCG is not a major cause of PPD (+) in adulthood

20. Vaccines in Pulmonary Medicine 1 2 3 Introduction to Vaccines Vaccine Immunology Current Adult Vaccines

21. Vaccine Development Human with ID Vaccination Inactivation Isolation Pathogen HumanwithoutID Killed Liveattenuated Protein Toxoid Pathogen PS-Protein PS Pathogen- Associated Molecular Patterns Vaccine Immunology

22. Host Immune Response A

23. Vaccine Immunology Host Immune Response Ag A Pathogen-Associated Molecular Patterns

24. Vaccine Immunology Host Immune Response Ag AB Pathogen-Associated Molecular Patterns Pattern Recognition Receptor

25. Vaccine Immunology Host Immune Response Ag DC AB Pathogen-Associated Molecular Patterns Pattern Recognition Receptor

26. Vaccine Immunology Host Immune Response Ag Lymph nodes Spleen DC AB C Ag Pathogen-Associated Molecular Patterns Pattern Recognition Receptor

27. Vaccine Immunology Host Immune Response Ag D B DC B cell activation Ag

28. Vaccine Immunology Host Immune Response Ag D B DC B cell activation Plasma cells PC IgM IgA IgG Ag

29. Vaccine Immunology Host Immune Response Ag E B DC MHC II Th

30. Vaccine Immunology Host Immune Response Ag E B DC MHC II Th Activated B cell Follicular helper T cells Follicular Dendritic cells Germinal Center Response B

31. Vaccine Immunology Host Immune Response Ag E B DC MHC II Th Activated B cell Follicular helper T cells Follicular Dendritic cells Germinal Center Response B PC IgM IgA IgG Plasma cells

32. Vaccine Immunology Host Immune Response Ag E B DC MHC II Th Activated B cell Follicular helper T cells Follicular Dendritic cells Germinal Center Response Bm B PC IgM IgA IgG Bm Plasma cells Memory B cells

33. Vaccine Immunology Host Immune Response Ag F B MHC II Th MHC I DC Activated B cell Follicular helper T cells Follicular Dendritic cells Germinal Center Response Bm B PC IgM IgA IgG Bm Plasma cells Memory B cells CD8

34. Vaccine Immunology Host Immune Response Ag F B MHC II Th MHC I DC Activated B cell Follicular helper T cells Follicular Dendritic cells Germinal Center Response Bm B PC IgM IgA IgG Bm Plasma cells Memory B cells CD8 Tc T cytotoxic cells

35. Vaccine Immunology Host Immune Response Ag F B MHC II Th MHC I DC Activated B cell Follicular helper T cells Follicular Dendritic cells Germinal Center Response Bm B PC IgM IgA IgG Bm Plasma cells Memory B cells CD8 Tc Tm Memory T cells T cytotoxic cells

36. Vaccine Immunology Host Immune Response Ag F B MHC II Th MHC I DC Activated B cell Follicular helper T cells Follicular Dendritic cells Germinal Center Response Bm B PC IgM IgA IgG Bm Plasma cells Memory B cells CD8 Tc Tm Bone Marrow PC Memory T cells T cytotoxic cells

37. Vaccine Immunology Host Immune Response Neutrophils Monocytes Dendritic cells B cells T cells PCBmThTc Vaccine

38. Vaccine Immunology Host Immune Response Neutrophils Monocytes Dendritic cells B cells T cells PCBmThTc Vaccine PS

39. Vaccine Immunology Host Immune Response Neutrophils Monocytes Dendritic cells B cells T cells PCBmThTc Vaccine PS PS-ProteinProteinToxoidKilled

40. Vaccine Immunology Host Immune Response Neutrophils Monocytes Dendritic cells B cells T cells PCBmThTc Vaccine PS PS-ProteinProteinToxoidKilled Live

41. Vaccine Immunology Host Immune Response Neutrophils Monocytes Dendritic cells B cells T cells PCBmThTc Vaccine PS PS-ProteinProteinToxoidKilled Live Duration of protection?

42. Vaccines in Pulmonary Medicine 1 2 3 Introduction to Vaccines Vaccine Immunology Current Adult Vaccines

43. Viral & Bacterial Pathogens 1. Influenza Virus 2. Varicella-Zoster Virus 3. Human Papillomavirus 4. Measles Virus 5. Mumps Virus 6. Rubella Virus 7. Hepatitis A Virus 8. Hepatitis B Virus 4. N. meningitidis 1. C. tetani 2. C. diphtheriae 3. B. pertussis 5. H. influenzae 6. S. pneumoniae 7. M. tuberculosis 8. S. typhi Current Adult Vaccines

44. Influenza Vaccine A/California/7/2009 (H1N1) A/Texas/50/2012 (H3N2) B/Massachusetts/2/2012 B/Brisbane/60/2008 Virus- neutralizing antibodies: IgA IgM IgG Recommended antigens for the 2014-2015 influenza season Current Adult Vaccines

45. Influenza Vaccine A/California/7/2009 (H1N1) A/Texas/50/2012 (H3N2) B/Massachusetts/2/2012 B/Brisbane/60/2008 Virus- neutralizing antibodies: IgA IgM IgG Recommended antigens for the 2014-2015 influenza season Trivalent Quadrivalent Inactivated Live-attenuated Intramuscular Intradermal Intranasal Low dose Regular dose High dose Eggs Cell-based DNA Current Adult Vaccines

46. Influenza Vaccine A/California/7/2009 (H1N1) A/Texas/50/2012 (H3N2) B/Massachusetts/2/2012 B/Brisbane/60/2008 Recommended antigens for the 2014-2015 influenza season Virus- neutralizing antibodies: IgA IgM IgG Viral strains in the vaccine Viral strains in the outbreak Effectiveness of Influenza Vaccine Current Adult Vaccines

47. Influenza Vaccine Effectiveness for the Prevention of Hospitalizations Due to Influenza Pneumonia Current Adult Vaccines

48. Influenza Vaccine Effectiveness for the Prevention of Hospitalizations Due to Influenza Pneumonia B/Brisbane/60/2008 Current Adult Vaccines

49. Influenza Vaccine Effectiveness for the Prevention of Hospitalizations Due to Influenza Pneumonia Current Adult Vaccines

50. Zoster (Shingles) Live Attenuated Zoster Vaccine (single dose) Live Attenuated Zoster Vaccine (single dose) Adults Rash / Acute Neuritis Complications Postherpetic neuralgia Ocular complications Motor neuropathy Encephalitis Stroke syndromes

51. Current Adult Vaccines Zoster Adult: Chronic Conditions Adult: Immunocompromising Conditions Adult: Immunocompromising Conditions Contraindicated 1 dose ? Cancer Drugs Pregnancy HIV 200 Asplenia Lung Heart Liver Kidney Diabetes Alcoholism Smoking 1 dose Adult: No Modifying Conditions 18 years 50 years 60 years No 1 dose ? FDA: Yes ACIP: No FDA: Yes ACIP: No

52. Current Adult Vaccines H. Influenzae H. influenzae serotype b (Hib) polysacharide vaccine H. influenzae nonencapsulated: nontypeable H. influenzae encapsulated: serotypes a, b, c, d, e, f H. influenzae serotype b (Hib) polysacharide conjugate vaccine

53. Current Adult Vaccines H. influenzae Indications for Adults Hib vaccine may be used in persons with: Asplenia Complement component deficiencies Sickle cell disease HIV Most respiratory infections in adults are caused by nontypeable H. influenzae (NTHi) Type b Polysaccharide Conjugate Vaccine (1 dose)

54. Current Adult Vaccines Pneumococcal S. pneumoniae: more than 90 serotypes Pneumococcal Polysaccharide Vaccine (PPSV 23 serogroups) Pneumococcal Polysaccharide Conjugated Vaccine (PCV 13 serogroups)

55. Vaccines for Adults 2 3 4 Introduction to Vaccines Vaccine Immunology Current Adult Vaccines 1 Principles of Immunization