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Vaccines in Pulmonary Medicine 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 1 Introduction to Vaccines 2 Vaccine Immunology 3 Current Adult Vaccines Introduction to Vaccines Viral & Bacterial Pathogens 1. Influenza Virus 1. C. tetani 2. Varicella-Zoster Virus 2. C. diphtheriae 3. Human Papillomavirus 3. B. pertussis 4. Measles Virus 4. N. meningitidis 5. Mumps Virus 5. H. influenzae 6. Rubella Virus 6. S. pneumoniae 7. Hepatitis A Virus 7. M. tuberculosis 8. Hepatitis B Virus 8. S. typhi Introduction to Vaccines Viral & Bacterial Pathogens 1. Influenza Virus 1. C. tetani 2. Varicella-Zoster Virus 2. C. diphtheriae 3. Human Papillomavirus 3. B. pertussis 4. Measles Virus 4. N. meningitidis 5. Mumps Virus 5. H. influenzae 6. Rubella Virus 6. S. pneumoniae 7. Hepatitis A Virus 7. M. tuberculosis 8. Hepatitis B Virus 8. S. typhi Variola Virus: Smallpox 1796 Introduction to Vaccines Viral & Bacterial Pathogens 1. Influenza Virus 1. C. tetani 2. Varicella-Zoster Virus 2. C. diphtheriae 3. Human Papillomavirus 3. B. pertussis 4. Measles Virus 4. N. meningitidis 5. Mumps Virus 5. H. influenzae 6. Rubella Virus 6. S. pneumoniae 7. Hepatitis A Virus 7. M. tuberculosis 8. Hepatitis B Virus 8. S. typhi Variola Virus: Smallpox 1796 Introduction to Vaccines Smallpox (Variola Virus) Human Disease Variola Virus Inhalation Smallpox Mortality 30 to 40% Introduction to Vaccines Smallpox (Variola Virus) Human Disease Variola Virus Inhalation Smallpox Mortality 30 to 40% 1980 Introduction to Vaccines Smallpox Human Disease Human Disease Variola Virus Variola Virus Inhalation Inoculation Smallpox Smallpox Mortality 30 to 40% Mortality 1 to 2% Introduction to Vaccines Smallpox: E. Jenner 1796 Human Disease Cow Disease Variola Virus Cowpox Virus Inhalation Smallpox Mortality 30 to 40% Human Cowpox Introduction to Vaccines Smallpox: E. Jenner 1796 Human Disease Human Disease Cow Disease Variola Virus Variola Virus Cowpox Virus Inhalation Inhalation Human Cowpox Smallpox Mortality 30 to 40% Vaccination No Smallpox Introduction to Vaccines Smallpox: E. Jenner 1796 Human Disease Human Disease Cow Disease Variola Virus Variola Virus Cowpox Virus Inhalation Inhalation Human Cowpox Cow Disease Smallpox Latin for Cow: Vacca CowpoxVaccine Virus Vaccination English: Mortality 30Spanish: to 40% Vacuna No Smallpox Introduction to Vaccines Smallpox: E. Jenner 1796 Inoculation Vaccination Introduction to Vaccines Tuberculosis Human Disease M tuberculosis Inhalation No TB Introduction to Vaccines Tuberculosis Human Disease M tuberculosis Inhalation Cow Disease M bovis No TB Introduction to Vaccines Tuberculosis Human Disease M tuberculosis Inhalation Cow Disease M bovis Vaccination More TB Introduction to Vaccines Tuberculosis Human with ID Isolation Pathogen Inactivation Human without ID Vaccination Introduction to Vaccines Tuberculosis Human with ID Isolation M. bovis Pathogen Inactivation Bacillus Calmette Guerin Human without ID Vaccination BCG Vaccine Since 1921 3 billion Introduction to Vaccines TB Vaccine Efficacy: Outcome Variable “Outcome” “Efficacy” Latent Infection 20% Protection Active Disease “Pulmonary TB” 50% Protection Active Disease “TB Meningitis” 75% Protection Active Disease “Death due to TB” 85% Protection 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 Vaccines in Pulmonary Medicine 1 Introduction to Vaccines 2 Vaccine Immunology 3 Current Adult Vaccines Vaccine Immunology Vaccine Development Human with ID Pathogen Isolation Live attenuated Inactivation Killed Pathogen Toxoid Human without ID Protein Vaccination PS-Protein PS PathogenAssociated Molecular Patterns Vaccine Immunology Host Immune Response A Vaccine Immunology Host Immune Response A Ag Pathogen-Associated Molecular Patterns Vaccine Immunology Host Immune Response A Pattern Recognition Receptor B Ag Ag Ag Pathogen-Associated Molecular Patterns Ag Vaccine Immunology Host Immune Response A Pattern Recognition Receptor B Ag Ag Ag Ag Ag Pathogen-Associated Molecular Patterns Ag Ag DC Vaccine Immunology Host Immune Response A Pattern Recognition Receptor B Ag Ag Ag Ag Ag Pathogen-Associated Molecular Patterns Ag Ag DC C Ag Ag Lymph nodes Ag Ag DC Spleen Vaccine Immunology Host Immune Response D Ag Ag Ag Ag DC Ag B cell activation B Vaccine Immunology Host Immune Response D Ag Ag Ag Ag DC Ag B cell activation B PC PC PC Plasma cells IgM IgA IgG Vaccine Immunology Host Immune Response E MHC II Ag Ag Th Ag DC Ag B Vaccine Immunology Host Immune Response E MHC II Ag Ag Germinal Center Response Th Ag DC Ag Activated B cell B B Follicular helper T cells Follicular Dendritic cells Vaccine Immunology Host Immune Response E MHC II Ag Ag Germinal Center Response Th Ag DC Ag Activated B cell Follicular helper T cells Follicular Dendritic cells B Plasma cells B PC PC PC IgM IgA IgG Vaccine Immunology Host Immune Response E MHC II Ag Ag Germinal Center Response Th Ag DC Ag Activated B cell Follicular helper T cells Follicular Dendritic cells B Plasma cells B PC PC PC Bm Bm Memory B cells IgM IgA IgG Vaccine Immunology Host Immune Response F MHC II Ag Ag DC Ag MHC I Germinal Center Response Th Ag Activated B cell Follicular helper T cells Follicular Dendritic cells B Plasma cells B PC CD8 PC PC Bm Bm Memory B cells IgM IgA IgG Vaccine Immunology Host Immune Response F MHC II Ag Ag DC Ag MHC I Germinal Center Response Th Activated B cell Ag Follicular helper T cells Follicular Dendritic cells B Plasma cells B PC CD8 T cytotoxic cells PC Tc PC Tc Bm Bm Memory B cells IgM IgA IgG Vaccine Immunology Host Immune Response F MHC II Ag Ag Germinal Center Response Th DC Ag MHC I Activated B cell Ag Follicular helper T cells Follicular Dendritic cells B Plasma cells B PC CD8 T cytotoxic cells PC Tc PC Tc Bm Tm Tm Bm Memory T cells Memory B cells IgM IgA IgG Vaccine Immunology Host Immune Response F MHC II Ag Ag Germinal Center Response Th DC Ag MHC I Activated B cell Ag Follicular helper T cells Follicular Dendritic cells B Plasma cells B PC CD8 T cytotoxic cells PC Tc PC Tc Bm Tm Tm Bm Memory T cells Memory B cells IgM IgA IgG PC Bone Marrow Vaccine Immunology Host Immune Response Neutrophils Vaccine Monocytes Dendritic cells B cells PC Bm T cells Th Tc Vaccine Immunology Host Immune Response Neutrophils Vaccine Monocytes Dendritic cells PS B cells PC Bm T cells Th Tc Vaccine Immunology Host Immune Response Neutrophils Vaccine Monocytes Dendritic cells PS PS-Protein Protein Toxoid Killed B cells PC Bm T cells Th Tc Vaccine Immunology Host Immune Response Neutrophils Vaccine Monocytes Dendritic cells PS PS-Protein Protein Toxoid Killed Live B cells PC Bm T cells Th Tc Vaccine Immunology Host Immune Response Neutrophils Vaccine Monocytes Dendritic cells PS PS-Protein Protein Toxoid Killed Live Duration of protection? B cells PC Bm T cells Th Tc Vaccines in Pulmonary Medicine 1 Introduction to Vaccines 2 Vaccine Immunology 3 Current Adult Vaccines Current Adult Vaccines Viral & Bacterial Pathogens 1. Influenza Virus 1. C. tetani 2. Varicella-Zoster Virus 2. C. diphtheriae 3. Human Papillomavirus 3. B. pertussis 4. Measles Virus 4. N. meningitidis 5. Mumps Virus 5. H. influenzae 6. Rubella Virus 6. S. pneumoniae 7. Hepatitis A Virus 7. M. tuberculosis 8. Hepatitis B Virus 8. S. typhi Current Adult Vaccines Influenza Vaccine Recommended antigens for the 2014-2015 influenza season A/California/7/2009 (H1N1) A/Texas/50/2012 (H3N2) B/Massachusetts/2/2012 B/Brisbane/60/2008 Virusneutralizing antibodies: IgA IgM IgG Current Adult Vaccines Influenza Vaccine Recommended antigens for the 2014-2015 influenza season A/California/7/2009 (H1N1) Virusneutralizing antibodies: IgA IgM IgG A/Texas/50/2012 (H3N2) B/Massachusetts/2/2012 B/Brisbane/60/2008 Trivalent Quadrivalent Inactivated Live-attenuated Intramuscular Intradermal Intranasal Low dose Regular dose High dose Eggs Cell-based DNA Current Adult Vaccines Influenza Vaccine Recommended antigens for the 2014-2015 influenza season A/California/7/2009 (H1N1) Virusneutralizing antibodies: IgA IgM IgG A/Texas/50/2012 (H3N2) B/Massachusetts/2/2012 B/Brisbane/60/2008 Effectiveness of Influenza Vaccine Viral strains in the vaccine Viral strains in the outbreak Current Adult Vaccines Influenza Vaccine Effectiveness for the Prevention of Hospitalizations Due to Influenza Pneumonia Current Adult Vaccines Influenza Vaccine Effectiveness for the Prevention of Hospitalizations Due to Influenza Pneumonia B/Brisbane/60/2008 Current Adult Vaccines Influenza Vaccine Effectiveness for the Prevention of Hospitalizations Due to Influenza Pneumonia Current Adult Vaccines Zoster (Shingles) Adults Rash / Acute Neuritis Complications Postherpetic neuralgia Ocular complications Motor neuropathy Encephalitis Stroke syndromes Live Attenuated Zoster Vaccine (single dose) Current Adult Vaccines Zoster Adult: Immunocompromising Conditions Cancer Drugs Pregnancy HIV <200 HIV >200 Asplenia Contraindicated ? 1 dose Adult: Chronic Conditions Lung Heart Liver Kidney Diabetes Alcoholism Smoking 1 dose Adult: No Modifying Conditions 18 years No 50 years 60 years FDA: Yes?ACIP: No 1 dose Current Adult Vaccines H. Influenzae H. influenzae nonencapsulated: nontypeable H. influenzae encapsulated: serotypes a, b, c, d, e, f H. influenzae serotype b (Hib) polysacharide vaccine H. influenzae serotype b (Hib) polysacharide conjugate vaccine 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) Current Adult Vaccines Pneumococcal S. pneumoniae: more than 90 serotypes Pneumococcal Polysaccharide Vaccine (PPSV 23 serogroups) Pneumococcal Polysaccharide Conjugated Vaccine (PCV 13 serogroups) Vaccines for Adults 1 Principles of Immunization 2 Introduction to Vaccines 3 Vaccine Immunology 4 Current Adult Vaccines