Lecture 26. Prevention and Control -- Vaccines

1. Lecture 26. Prevention and Control -- Vaccines Flint et al., chapter 19, pp. 703 - 725

2. How do we acquire immunity?

3. Passive Immunity in Infants

4. Artificial Passive Immunity • Gamma globulin • Ig’s from pooled blood of at least 1,000 human donors • variable content • non-specific • Specific immune globulin (SIG) • higher titers of specific antibodies • Antisera and antitoxins of animal origin

5. Antibody and effector T-cells are the basis of protective immunity • Primary infection stimulates an initial immune response. • A second infection is “inapparant” because it provokes no symptoms. • However, it does re-stimulate and fine tune the immune response. • Years later, memory B- and T-cells can become reactivated upon infection, protecting the individual from disease

6. Artificial Active Immunity • Vaccination (Immunization) • exposing a person to material that is antigen but NOT pathogenic.

7. History of Vaccination: Smallpox • Smallpox killed or maimed 10% of humankind. • Killed > 300,000,000 people in the 20th century alone • Ancient Chinese history: a once in a lifetime disease. • 11th century China and India: “Variolation” • Scratch a healthy person with pus from infected person • If they don’t die, they are immune for life

8. Vaccination • May 14, 1796, Edward Jenner • Noted that milkmaids got cowpox, but not smallpox. • Injected pus from a cowpox lesion under the skin of a child • Waited 2 weeks • Deliberately infected the child with smallpox. • The boy survived • (Today, Jenner would be majorly sued, would lose his license, be put on trial, get a good lawyer, write a book, and do the talk show circuit…Just like Michael Jackson’s doctor!)

9. History of Vaccination • Despite Jenner’s success, it took 100 years til the next vaccine. • 1881, Louis Pasteur: coined the word Vaccine. • Used dried spinal cord from rabid rabbit to create a rabies vaccine. • Also developed vaccines to fowl cholera and anthrax • July 6, 1885: 9 year old Joseph Meister who was badly bitten by a rabid dog. • Although Pasteur was not a licensed physician and faced legal risks, the boy would most certainly have died without treatment like many before him. • Pasteur decided to treat the boy nevertheless and inoculated Joseph with rabies vaccine that had been tested only on dogs previously. • The risk paid off and the boy recovered dramatically.

10. Large scale vaccination programs Fig. 19.1 • Dramatic improvements in public health. • Nobody in this room has had… • Smallpox, Polio, Measles, Chickenpox • Mumps, Rubella • …Because of vaccination • Smallpox is the only human disease to ever be eradicated

11. Characteristics of a good vaccine • Safe • Few side effects • Give long lasting, appropriate protection • Low in cost • Stable with long shelf life (no special storage requirements) • Easy to administer • Inexpensive • Public must see more benefit than risk

14. Types of vaccines • whole agent • subunit • recombinant • individual parts alone

15. epitopes epitopes Whole agent vaccines -- Killed using heat or formaldehyde Killed virus Live virus Inactivated polio vaccine (Salk) Influenza (Classic)

16. oral polio vaccine (Sabin), MMR (measles, mumps, rubella) Influenza -- Flumist TM Whole agent vaccines -- Attenuated • attenuated - a process that lessens the virulence of a microbe

17. Vaccines stimulate immune memory • Killed virus vaccine requires multiple doses (booster shots) to adequately stimulate a protective immune response • Live virus vaccines replicate in the host. • No requirement for boosters.

18. Attenuation of viruses by passage through non-human cells • Pathogenic virus isolated from patient, grown in human cells • Infect monkey cells with cultured virus • Virus acquires many mutations that allow it to grow well in monkey cells • Mutations make the virus unable to grow well in human cells •  Vaccine candidate 1 2 3 4

19. Advantages for live vaccines • multiply like natural organism • require fewer doses and boosters • long-lasting • Disadvantages for live vaccines • special storage • back mutation • side effects

20. Live attenuated Sabin oral poliovirus vaccine

21. Construction of recombinant attenuated virus • Isolate virus • Clone genome • Isolate virulence gene • Mutate or delete virulence gene • Resulting virus is • Viable • Immunogenic • Not virulent • Can be used as a vaccine

22. Subunit vaccines • Single antigen or mixture of antigens • Safer (cannot reproduce) • However, often less effective than whole agent vaccines • Can be costly • Always require boosters

23. Overcoming Subunit vaccine problems • Multiple doses - booster shots • Use adjuvants • prolongs stimulation of immune response • works by trapping the antigens in a chemical complex and releases them slowly

24. Vaccine delivery systems and adjuvants ISCOMS as peptide delivery systems Fig. 19.9

25. Recombinant vaccines • Genetic engineering approach • Hepatitis B • Vaccina or adenovirus alteration

26. Create a recombinant plasmid containing a gene encoding a specific antigen. • Engineer in sequences • Enabling it to be expressed in humans • Passaged through bacteria • Introduce it into humans • Let the human cells produce the antigen • Present it to T-cells • Provoke immune response DNA vaccines

27. Representative results of DNA vaccine trials