1. 8May06KL Vadheim Lecture 11 Introduction to Vaccines MedCh 401 Spring 2006 Kirsten L. Vadheim, Ph.D.

2. 8May06KL Vadheim Lecture 12 Why study vaccines? Patient education –Pharmacists are often the most accessible medical professional –too many choices! Flu: yes or no? live or inactivated? Pneumococcal? Meningococcal? TD booster?

3. 8May06KL Vadheim Lecture 13 Why study vaccines? II –Misinformation Only children get pertussis - no MMR vaccination causes autism - no HepB vaccination is linked to development of autoimmune disorders - no Childhood vaccinations increase the risk of SIDS - no SV40-contaminated polio vaccine caused cancer - inadequate data

4. 8May06KL Vadheim Lecture 14 More reasons to study vaccines Vaccine administration –you may have to give them! New vaccines, changing recommendations Rotavirus Lyme disease OPV to IPV Pertussis Public health

5. 8May06KL Vadheim Lecture 15 History Variolation –c. 16th centure China –1721 - Lady Mary Montagu brought it to England –1774 - cattle breeder Benjamin Jesty inoculated his wife and children with cowpox to protect them from a smallpox epidemic

6. 8May06KL Vadheim Lecture 16 History II Edward Jenner –1798 Variolae Vaccinae –demonstrated that cowpox could be passed directly from one infected person to another, providing large-scale, effective inoculation against smallpox 1840: variolation made a felony in England

7. 8May06KL Vadheim Lecture 17 History III Louis Pasteur –1880: attenuation of Pasteurella multocida to protect against chicken cholera –1881: developed animal vaccine for anthrax, demonstrating that one could create standardized, reproducible vaccines at will –1885: successful vaccination of first human (Joseph Meister, rabies)

8. 8May06KL Vadheim Lecture 18 History III Killed vaccines –Salmon and Smith, 1886; killed hog cholera virus vaccine (actually a bacterial vaccine against salmonellosis) –1896-7: Human typhoid, cholera, plague vaccines

9. 8May06KL Vadheim Lecture 19 History IV Paul Ehrlich –1897: receptor theory of immunity explained toxin-antitoxin interactions –active and passive immunity –‘magic bullets’ Emil von Behring –1890: Development of diphtheria antitoxin as protection during diphtheria epidemics

10. 8May06KL Vadheim Lecture 110 History V Early 1900s –23 U.S. children died from diphtheria antitoxin derived from horse infected with tetanus post-WWII progress on viral vaccines –virus propagation in stationary cell culture –CPE

11. 8May06KL Vadheim Lecture 111 History VI Polio –Salk et al.: formalin-inactivated vaccine –Sabin: live attenuated vaccine –Cutter incident inadequately inactivated vaccine 204 cases of type I polio

12. 8May06KL Vadheim Lecture 112 Immune Globulins Immediate transfer of passive immunity –Homologous pooled human antibody –Homologous human hyperimmune globulines –Heterologous hyperimmune serum (antitoxin) Tetanus, Rabies Polyclonal (RSV-IGIV) Monoclonal (Palivizumab)

13. 8May06KL Vadheim Lecture 113 Comparison of Maximum and Current Morbidity

14. 8May06KL Vadheim Lecture 114 Licensed Vaccines I FDA/CBER BLA –IND –Clinical trials –Extensive agency review –Inspection –Approval

15. 8May06KL Vadheim Lecture 115 Licensed Vaccines II Post-approval –Lot release –Biennial inspections –Annual reports –Pharmacovigilence –21CFR601.12

16. 8May06KL Vadheim Lecture 116 Licensed Bacterial Vaccines Anthrax BCG DTaP Haemophilus influenzae b Meningococcal Plague Pneumococcal Typhoid - Ty21a and Vi

17. 8May06KL Vadheim Lecture 117 Licensed Viral Vaccines Hep A Hep B Flu JEV Measles Mumps Polio Rabies Rotavirus Rubella Rotavirus Smallpox Varicella Yellow Fever

18. 8May06KL Vadheim Lecture 118 Types of Vaccines I Prophylactic Therapeutic

19. 8May06KL Vadheim Lecture 119 Types of Vaccines II

20. 8May06KL Vadheim Lecture 120 Types of Vaccines III

21. 8May06KL Vadheim Lecture 121 The Perfect Vaccine 100% effective Oral dosage form No adverse effects Highly immunogenic –life-long immunity –no boosters required Cheap Stable at room temperature –no cold chain required

22. 8May06KL Vadheim Lecture 122 Combination vaccines DT DTaP DTaP-HepB-IPV HepA-HepB MM MMR MMRV