Even 2,500 Years Ago, People Knew Immunity Worked.

1. Even 2,500 Years Ago, People Knew Immunity Worked. • Greek physicians noticed that people who survived smallpox never got it again. • The insight: Becoming infected by certain diseases gives immunity.

2. How does vaccination work? Expose the patient to an Antigen • A live or inactivated substance (e.g., protein, polysaccharide) derived from a pathogen (e.g bacteria or virus) capable of producing an immune response

3. How does vaccination work? Expose the patient to an Antigen • A live or inactivated substance (e.g., protein, polysaccharide) derived from a pathogen (e.g bacteria or virus)capable of producing an immune response If the patient is subsequently exposed to infectious agent carrying this Antigen they will mount a faster immune response

4. It works like this Patientexposed to pathogen Carrying antigens A and B Molecular Biology of the Cell Alberts et al

5. Vaccines can be divided into two types • Live attenuated • Inactivated

6. Inactivated Vaccines fall into different categories Whole • viruses • bacteria • Individual proteins from pathogen • Pathogen specific complex sugars Fractional

7. Live Attenuated Vaccineshave several advantages • Attenuated (weakened) form of the "wild" virus or bacterium • Can replicate themselves so the immune response is more similar to natural infection • Usually effective with one dose

8. Live Attenuated Vaccinesalso have several disadvantages • Severe reactions possible especially in immune compromised patients • Worry about recreating a wild-type pathogen that can cause disease • Fragile – must be stored carefully MMWR, CDC

9. A number of the vaccines you receivedwere live Attenuated Vaccines • Viral measles, mumps, rubella, vaccinia, varicella/zoster, yellow fever, rotavirus, intranasal influenza, oral polio • BacterialBCG (TB), oral typhoid

10. Inactivated Vaccines are the other option Pluses • No chance of recreating live pathogen • Less interference from circulating antibody than live vaccines

11. Inactivated Vaccines are the other option Minuses • Cannot replicate and thus generally not as effective as live vaccines • Usually require 3-5 doses • Immune response mostly antibody based

12. Inactivated Vaccines are alsoa common approach today • Viral polio, hepatitis A, rabies, influenza* • Bacterial pertussis*, typhoid* cholera*, plague* Whole-cell vaccines *not used in the United States

13. Other Inactivated Vaccinesnow contain purified proteinsrather than whole bacteria/viruses • Proteins hepatitis B, influenza, acellular pertussis, human papillomavirus, anthrax, Lyme • Toxins diphtheria, tetanus

14. Modern molecular biologyhas offered new approaches to make vaccines • Clone gene from virus or bacteria • and express this protein antigen • in yeast, bacteria or • mammalian cells in culture

15. Modern molecular biologyhas offered new approaches to make vaccines 2. Clone gene from virus or bacteria Into genome of another virus (adenovirus, canary pox, vaccinia) And use this live virus as vaccine

16. This allows T cells to recognize HIV infected cells, for example, and even internal proteins like reverse transcriptase can serve as antigens An effective vaccine must get around the strategies HIV uses to evade the immune system

17. To begin we need to ask some key questions Whatshould vaccine elicit? Neutralizing antibodies to kill free virus T cell response to kill infected cells OR

18. To begin we need to ask some key questions Whatshould vaccine elicit? Neutralizing antibodies to kill free virus T cell response to kill infected cells OR OR BOTH?