Understanding Vaccines: History, Mechanisms, and Future Development

1. Chapter 16Immunizations and Immunity

2. Amazing Fact “An estimated 2.1 million people around the world died in 2002 of diseases preventable by widely used vaccines.1 With an investment of 3 billion USD a year, every child in the developing world could receive complete immunization coverage.2 1 World Health Organization. Immunization Against Diseases of Public Health Importance. March 2005.) 2 UNICEF. Immunize Every Child: GAVI Strategy for Immunization Services. February 2000)

3. History • Edward Jenner • Cowpox and smallpox experiments • Louis Pasteur • Cholera work • Originator of term “vaccine”

4. Mechanisms of Immunity • Innate immune system • Present from birth • Does not differentiate challenge • Adaptive immune system • Synonyms: acquired or specific immunity • Responds to specific challenges

5. Innate Immunity • Nonspecific response • Anatomic barriers • Skin and mucosal membranes • Physiologic barriers • Acidity and chemical mediators • Phagocytosis • Neutrophils and macrophages • Inflammation • Antibacterial and stimulatory effects • Natural killer cells • Tumor cytotoxicity

6. Figure 1: Phagocytosis

7. Adaptive Immunity • Responds to specific antigenic challenge • Cells involved • T lymphocytes (T cells) • B lymphocytes (B cells) • Types of adaptive responses • Cell-mediated (cellular) immunity • Humoral immunity

8. Cell-mediated Immunity • Involves T lymphocytes • Derived from cells in the bone marrow • Mature and differentiate in the thymus • Help eliminate intracellular organisms • Present protein antigens to B cells • Secrete cytokines • Develop specific functions after antigenic exposure

9. Memory cell T lymphocyte Antigen Cytotoxic cell Helper cell Suppressor cell Lymphocytic stem cell Antibody producing cell Memory cell B lymphocyte Antigen Figure 2: Functional lymphoid populations following antigenic stimulation

10. Humoral Immunity • Involves B lymphocytes • Primary defense against extracellular organisms • Recognize antigenic determinants (epitopes) leading to antibody production by plasma cells • Antibodies produced • IgM, IgG, IgA, IgD, IgE

11. Humoral Immunity • Chief functions of antibodies • Neutralize bacterial toxins • Neutralize viruses • Promote phagocytosis • Activate inflammatory response • Antibodies at work • Primary and secondary responses

12. 1st exposure to antigen 2nd exposure to antigen Antibody Titer Time Figure 3: Primary and secondary response curves

13. Active and Passive Immunity • Active immunity • Immunocompetent individual produces immune products after exposure to foreign organism • Immune products: antibodies, memory cells • May be naturally developed (natural infection) or artificially acquired (vaccine)

14. Active and Passive Immunity • Passive immunity • Involves transfer of preformed antibodies • May involve natural acquisition (maternal- fetal transfer) or may be acquired (injection of immunoglobulin)

15. Active and Passive Immunity • Differences in protection • Active immunity • Long-term protection due to production of memory cells • Passive immunity • Short-term protection due to lack of memory cell production

16. Vaccines • Mimic natural infection • Stimulate the immune system • Key requirements for success • Immunologic memory • Specificity

17. Vaccines • Goal • Stimulate memory T and B cells • To induce specific immunity • Eliminate organisms • Neutralize bacterial toxins

18. Vaccines • Live, attenuated vaccine • Contains weakened (attenuated) form of live organisms • Advantage: • produces strong cellular and humoral responses • Disadvantages: • chance organism may become virulent again • requires refrigeration

19. Vaccines • Inactivated vaccines • Killed organisms • Advantages: • Safer and more stable than live vaccines • Usually do not require refrigeration • Some may be freeze-dried • Disadvantage: • May stimulate weaker response than live vaccines

20. Vaccines • Toxoid vaccines • Treated microbial toxins • Advantage: • Stimulate strong antibody responses that eliminate harmful toxins

21. Vaccines • Subunit vaccines • Composed of selected microbial epitopes • Often administered with adjuvants such as aluminum salts • Advantages: • Greater specificity • Adverse reactions less likely

22. Vaccines • Conjugate vaccines • Couple polysaccharide antigens to protein carrier • Advantage: • Better recognition by the immune system to stimulate strong immune response especially in infants and children

24. Future Vaccines • DNA vaccines • Use organism’s genes to invoke antigen expression in host • Recombinant vector vaccines • Use attenuated organism to introduce organism’s DNA into host • Hurdles to vaccine development • Mutation of organisms especially viruses • Genetic complexity of certain organisms

25. Immunization of Selected Groups • Childhood immunizations • Recommendations approved yearly by • Centers for Disease Control and Prevention (CDC) • American Academy of Pediatrics • American Academy of Family Physicians

26. Immunization Schedule

27. Immunization of Selected Groups • Adult immunizations • Influenza • Pneumococcal • Travelers • Depends on site of travel • Workers exposed to biological agents in work environment • Anthrax • Smallpox

28. Effectiveness of Vaccines • Generally effective in most populations • Poor-responders • Small group of individuals • Herd (community) immunity • Immunity developed by group of vaccinated individuals • Impediments to achieving herd immunity • Concerns regarding adverse side effects • Costs of vaccines

29. Barriers to Widespread Coverage • Developed world • Access and cost issues among certain populations • Language barriers • Failure to obtain booster shots or complete series • Fears concerning vaccination • Underestimation of disease risk

30. Barriers to Widespread Coverage • Developing Countries • Logistical issues • Storage requirements • Poor infrastructure • Lack of roads • Personnel issues • Shortage of health care workers