Vaccines in Immunobiology and Medicine

1. Vaccines inImmunobiologyandMedicine Folder title: VaccinesNoTP Updated: December 04, 2012

2. Immunology in Human and Animal Health and Disease Why do we want to know about Immunology? What does it tells us about ourselves and about biology? What can it do for us? As a tool in biomedical research? As a diagnostic and therapeutic modality in clinical and veterinary medicine? What can it do to us, as a source of pathology?

3. Immunology in Human and Animal Health and Disease What can we make it do for us?

4. KEY FEATURES OF SPECIFIC ADAPTIVE IMMUNITY IN HISTORY Immunity Exists Freedom from Plague after Surviving First Exposure Susceptibility to Other Diseases Even After Surviving Plague Immunity is Specific Deliberately Induce Small-pox to Protect Against Later Exposure Immunity has Memory Induce Non-pathogenic Cow-pox to Protect Against Virulent Small-pox (Vaccination) Related Antigens are Cross-Reactive Antigens can be separated from pathogenic features Resistance to Chicken Cholera after Surviving Exposure to Weakened Chicken Cholera Bacilli (Attenuated Vaccines)

5. Why Not: • Deliberately expose people to the disease organism under controlled conditions? • Expose people to the attenuated non-pathogenic organism? • Expose people to a related organism that is like the pathogenic one but doesn’t cause disease? (e.g. vaccinia virus from Cox-pox) • Get antigens from the pathogenic organism separate from disease-causing properties and use those on people ?

6. Vaccines in Human and Veterinary Medicine What have they done for us? What do we have now? How do they work? What don't we have? Why not? How can we get what we need? How can we improve their immunogenicity? Can vaccines for millions of healthy persons cause problems ? Can we make them faster in response to changes in pathogens?

7. Oakwood Cemetery Burials Section 29 Survey by Tom Fondy 10-Nov-96 Filename: OakSec29.doc Age in Name Born Died Years Remarks Robbie Bonta 1868 1875 7 March 22, 1875, Age 6 yrs & 8 mos.; Son of Samuel Katherine T. Bonta 1864 1945 81 Frank M. Bonta 1845 1939 94 Helen A. Plumb 1853 1886 33 Jan. 20, 1886; Wife of Frank M. Bonta Laura J. Benner 1850 1876 25 Died Feb. 9, 1876; Wife of Frank M. Bonta Samuel 1873 1874 1.5 Son of F & L Bonta; Aged 1 yr & 7 mos George L. Bonta 1848 1922 74 H. Benner 1876 1888 12 Born Feb. 9, 1876 (See Laura S. Benner) Blank Unk Unk Unk Next to H. Benner; Tombstone is Blank Frankie L. Curtis 1864 1875 11 Born Sept. 22, 1864; Died Feb. 14, 1875 Frances B. Curtis 1844 1932 88 Nathan L. Curtis 1836 1922 86 Roger L. Jones 1872 1951 79 Mary C. Jones 1875 19?? Fannie Lathrop 1871 1879 8 Died Dec. 27, 1879; Age 8 yrs, 8 mos, 3 dys Rachel Amelia Cody 1840 1840 0.1 d. August 8, 1840; Age 6 wks and 4 dys; Daughter of Narcissa & Niel? Cody Unk Unk Faded (Could be Narcissa or Niel Cody) Missing Unk Unk Unk Unknown 1800 1883 83 George Chapman Lathrop 1811 1898 87 Unknown Unk Unk Unk Tombstone Toppled George Nelson 1847 1849 2 Son of Benjamin & Permela Lathrop George Chapman 4 Aged 3 yrs, 10 mos, 16 dys Average Age: 43.1 Notes: 10 died aged 6 wks to 33 yrs. 50% of Identifiable Dates! 8 died aged 74 to 94. (Also a child. Should be blue) 19 Identifiable persons with dates. 8 are children 0 to 12 years of age! See Verses by TPFondy at http://tpfondy.mysite.syr.edu/ Song of the Oakwood Children Verses and Self-running Presentation

8. Song of the Oakwood Children See Verses by TPFondy at http://tpfondy.mysite.syr.edu/ Verses and Self-running Presentation

9. Immunobiology Class Experiment Oakwood Cemetery: Dec. 1999 63 Students each surveyed a section in Oakwood with Markers from the 19th Century and a section with markers after 1940. Tombstones prior to 1900 (Left Half of Table) Tombstones after 1940 (Right Half) Summary of Results Next Slide Table Following Slide Graphic

10. Summary of Class Experiment: BIO 447 Immunobiology Oakwood Cemetery Deaths by Age: 19th Century vs Post 1940 Prior to 1900After 1940 MedianMean0 to 15 yrs16 to 40 yrs Median Mean0 to 15 yrs16 to 40 yrs 50.6 54.3 15.2% 16.5% 67.3 70.8 2.2% 6.2% 48 out of 58 sections have child deaths 18 out of 58 sections have child deaths 55 out of 58 Sections have young adult deaths 35 out of 58 sections have young adult deaths Approximately 180 deaths prior to age 15 Approximately 25 deaths prior to age 15 “Now we know and treat and seldom do we suffer death to stalk the nursery” (Song of the Oakwood Children)

11. Median Survival: 50.6 yrs Median Survival: 67.3 yrs 180 Children 25 Children

12. A 19th Century American Family History Willie: 1850-1962 Eddie: 1846-1850 Thomas (“Tad”)1853 - 1871 Robert: 1843-1926 (Had a son: 1873 – 1890; Two daughters: 1869-1938; 1875-1948)

13. Note on a Syrian Playground, November, 2012 Rachel, they make war on children. Now we die by our brothers’ hand! (Song of the Oakwood Children)

15. What Have Vaccines Done For Us?(See Figure 18-1 Kuby, 3rd Edition)Antiviral Vaccines, From Roitt, 4th Edition, Figure 19.3Data for U.S. VacSave1

16. What Have Vaccines Done For Us?(See Figure 18-1 Kuby, 3rd Edition)Antiviral Vaccines, From Roitt, 4th Edition, Figure 19.3Data for U.S. VacSave2

17. What Have Vaccines Done For Us? Greatest Single Cause of Death for Humankind Since the Beginning of Civilization: Smallpox Deaths from Smallpox 1977 - 2004: 0

19. Measles Vaccine (Introduced 1962) Reappearance in 1980’s in unvaccinated or singly vaccinated young people

20. Passive and Active Immune Protection Passive: Transfer of Pre-existing Immune Response Naturally from Mother to Child Trans-placental Breast Feeding Artificially in Medical Treatment Adoptive - Donor to Recipient Usually Antibodies; Could be Lymphocytes Anti-toxin Antibodies: Treatments for toxins already present: Rabies, Diphtheria, Tetanus, Botulinus Poisoning Provides Limited Duration Prophylaxis Active: Induce Immune Response Directly in Protected Individual

22. Active ImmunizationProphylactic Immunity based on Immunological Memory Controlled Artificial Infection • Active Disease-causing organism: Smallpox Pustule Exudates - Variolation • Cross-reactive related live organism: Vaccinia (cowpox virus) - Vaccination • Attenuated Live Organisms • Inactivated Killed Organisms • Inactivated Exotoxins - Diphtheria, Tetanus • Purified Macromolecular Antigens • Bacterial Capsular Polysaccharides • Membrane Antigens: Plasma Membrane or Virus Envelope • Cloned Antigenic Gene Products • Synthetic Antigens • Anti-idiotypic Antibodies (antigen mimics) • DNA vaccines

24. Live Attenuated Vaccines Against Viral Diseases • Polio (Sabin Vaccine) - Also Use Killed Vaccine (Salk) • Measles (“Rubeola”) • Mumps • Rubella (“3-Day Measles” or “German Measles” • Yellow Fever • Hepatitis A (Live and killed versions) Against Bacterial Disease • Tuberculosis

25. Killed Whole Organism Vaccines Against Viral Diseases • Polio (Salk Vaccine) - Also Use Attenuated Live Vaccine (Sabin) • Rabies • Influenza (strain-specific only) • Hepatitis A (Live and killed versions) Against Bacterial Disease • Pertussis (Whooping Cough) • Typhoid • Cholera (combined with toxin subunit vaccine) • Plague (short-term protection only) • Pneumococcal Pneumonia

26. Anti-Toxin Vaccines Formalin-inactivated exotoxin Formalin-inactivated exotoxin Exotoxin subunit (beta subunit) Clostridium tetani Corynebacterium diphtheriae Vibrio cholerae

27. Anti-Diphtheria Toxin Vaccine(Figure 19-5 Roitt, 4th Edition)

28. Purified Macromolecular Antigen Vaccines Capsular Polysaccharides – Must Be Conjugated to Protein Carriers to Get Memory Responses • Hemophilus influenza B (Bacterial meningitis) • Neisseria meningitidis • Streptococcus pneumoniae Recombinant Cell-Surface Antigen • Hepatitis B

29. Vaccines Generally Given to All Tetanus (Toxoid) Diphtheria (Toxoid) Pertussis (Killed virus) • Given Together as DPT; Periodic Boosters for Tetanus & Diphtheria Required • Polio (Killed or Attnenuated Live Virus) Measles (Attenuated live virus) Mumps (Attenuated live virus) Rubella (Attenuated live virus) Chicken Pox (Attenuated live Varicella Zoster) Hemophilus Influenzae (Polysaccharide capsular component); For bacterial meningitis (not related to flu vaccine)

30. Vaccines for Groups at Special Risk Tuberculosis (BCG) Depending on Locale and Travel Hepatitis B (Recombinant Surface Ag) • Medical personnel; drug addicts; contacts Rabies - Animal workers or post exposure Influenza (Killed virus strains) - At risk and Elderly Pneumococcal pneumonia (Killed bacteria) - Elderly Meningitis (Capsular Polysaccharide) - Yellow fever (Killed pathogen) Typhoid (Killed pathogen) Cholera (Mutant pathogen; Toxoid Subunit) Hepatitis A (Killed or attenuated virus) Varicella-zoster (Attenuated virus) -

31. What Vaccines Don't We Have? Viral Diseases • HIV - Presence of variants and Immunosuppression Ignorance of immunogenic antigens to use • Herpes Viruses (Papilloma virus vaccine announced Fall, 2002) • Adenoviruses, Rhinoviruses - Multiple types Bacterial Diseases • Staphylococci • Group A Streptococci • Mycobacterium leprae (Some benefit from BCG) • Treponema pallidum (syphilis) • Non-Hemophilus and Non-Neisseria Bacterial Menigitis Fungal Pathogens • Candida • Pneumocystis

32. More Vaccines That We Don't Have Protozoa • Malaria • Trypanosomiasis Sleeping Sickness Chagas Disease - Autoimmunity and Immunosupression • Leishmaniasis Multicellular Parasites - Worms • Schistosomiasis Prophylactic and Therapeutic Cancer Vaccines

33. How Can We Get What We Don't Have? Combination Epitope Vaccines (Multivalent Subunit Vaccines ) Delivery Vehicles and Adjuvants Anti-Idiotype Vaccines Naked DNA Vaccines Engineered Vector and Antigen-presenting Cell Vaccines Mucosal-Active (IgA Isotype) Vaccines

34. Non-Scientific Problems with Vaccines Medical Risks to Individuals vs "Herd Immunity" Immediate Risks to the Individual Long-term Benefits the the Group and the Individual Very low percentage risks multiplied over huge populations Side-Reactions, Limited Efficacy, Limited Duration Costs and Ability to Pay Geographical Distribution "Orphan" and "Third World" Diseases Limitations in Vaccine Production for Diseases with High Rate of Strain Variation Autonomy, Parental rights, Religious Freedom Public Acceptance and Ignorance of History

35. Measles Vaccine (Introduced 1962) Reappearance in 1980’s in unvaccinated or singly vaccinated young people

36. Risks from Whooping Cough Disease(Pertussis) vs. Risks from Pertussis Vaccine Whooping Cough Disease Seizures: 1 in 25 to 1 in 50 Encephalytis: 1 in 1,000 to 1 in 4,000 Brain Damage: 1 in 2,000 to 1 in 8,000 Death: 1 in 200 to 1 in 1,000 Pertussis Vaccine Seizures: 1 in 1,750 Encephalytis: 1 in 110,000 Brain Damage: 1 in 310,000 Death: 1 in 1,000,000 Difference in Death Rate: Natural Exposure to Whooping Cough vs Exposure to Pertussis Vaccine: 1,000-fold to 5,000-fold increased Risk

37. View Animation on Textbook Web-site: (Linked to Course Home Page) - Vaccines Also Molecular Visualizations: Influenza Hemmagglutinin Survey of Oakwood Cemetery done by BIO 447 Class, 1999: Section with Burials Prior to 1900 vs Sections with Burials after 1940 Song of the Oakwood Children: Rachel Amelia Cody, June 1840

38. (Your response is anonymous. No name will be recorded)With respect the use of Turning Point NXT Transmitter system in BIO 447 and its contribution to the standards of the course:The next slide will ask what you think of how well the system works • Outstanding • Good • Acceptable • Poor • Terrible Response Grid 0 of 94

39. (Your response is anonymous. No name will be recorded)With respect to how well the Turning Point NXT Transmitter system works in the classroom: • It works outstandingly well • It works well • It is OK • It is pretty unreliable and hard to make work • It doesn’t work well at all 0 of 94

40. Anti-Idiotypic Antibodies (Figure 19.9, Roitt, 4th Edition) IdioVacc