1. Please read Chapters 5, 6 and 7 of your vaccine text for next Wednesday’s lecture Chapters 9, 17 and 8 for next Friday’s lectures Valerie Daggett ppt files for first 2 lectures Past exams

2. Principles of Vaccination Self vs. nonself Protection from infectious disease Usually indicated by the presence of antibody Very specific to a single organism Immunity

3. Principles of Vaccination Protection produced by the person's own immune system Usually permanent Protection transferred from another person or animal Temporary protection that wanes with time Active Immunity Passive Immunity

4. Principles of Vaccination A live or inactivated substance (e.g., protein, polysaccharide) capable of producing an immune response Protein molecules (immuno- globulin) produced by B lymphocytes to help eliminate an antigen Antigen Antibody

5. 3 main classes of antibodies IgGbloodmonomer IgMmuscle/bloodpentamer sIgAmucosal surfacedimer Not all immune responses are equal IgG may not be all that effective for something colonizing the intestines or nasal passages

6. Constant Region Hypervariable Region Light Chain Heavy Chain Antigen Binding Region Structure of an anti-influenza hemagglutinin antibody

7. Hemagglutinin Structure of an influenza hemagglutinin- antibody complex Human antibody

8. Rotate ~90  Add all atoms Binding surface of hemagglutinin- antibody complex

9. Antigen residues at the interface = epitope Interface of hemagglutinin- antibody complex Epitopes are typically ~5 residues long

10. hemagglutinin antibody Space-filling mode Grey now = mainchain of hemagglutinin Epitopes reside in turns and loops Interface of influenza hemagglutinin-antibody complex

11. Passive Immunity Transfer of antibody produced by one human or other animal to another Temporary protection (weeks – months) Transplacental most important source in infancy

12. Sources of Passive Immunity Almost all blood or blood products Homologous pooled human antibody (HepA, measles) Homologous human hyperimmune globulin (HepB, tetanus, varicella, rabies) Heterologous hyperimmune serum (antitoxin-diphtheria, botulism)

13. Passive Immunization Polymeric vs Monomeric antibodies IM preps---contain Ab aggregates and other serum components If given IV they can activate complement system → anaphylaxis and cardiovascular collapse

14. Passive Immunization IV preps --- stabilizers added to give monomeric IgG Okay in blood stream

15. Vaccination Active immunity produced by vaccine Immunity and immunologic memory similar to natural infection but without risk of disease (transparency)

16. Classification of Vaccines Live attenuated – viral – bacterial Inactivated

17. Inactivated Vaccines viruses bacteria protein-based – toxoid – subunit polysaccharide-based – pure – conjugate Whole Fractional

18. Principles of Vaccination General Rule The more similar a vaccine is to the disease-causing form of the organism, the better the immune response to the vaccine.

19. Live Attenuated Vaccines Attenuated (weakened) form of the "wild" virus or bacterium Must replicate to be effective Immune response similar to natural infection Usually effective with one dose* *except those administered orally

20. Live Attenuated Vaccines Severe reactions possible Interference from circulating antibody Fragile – must be stored and handled carefully

21. Live Attenuated Vaccines Viral measles, mumps, rubella, vaccinia, varicella/zoster, yellow fever, rotavirus, intranasal influenza, oral polio* Bacterial BCG, oral typhoid *not available in the United States

22. Inactivated Vaccines Cannot replicate Generally not as effective as live vaccines Less interference from circulating antibody than live vaccines Generally require 3-5 doses Immune response mostly humoral Antibody titer may diminish with time

23. Inactivated Vaccines Viral polio, hepatitis A, rabies, influenza* Bacterial pertussis*, typhoid* cholera*, plague* Whole-cell vaccines *not available in the United States

24. Inactivated Vaccines Subunit hepatitis B, influenza, acellular pertussis, human papillomavirus, anthrax, Lyme* Toxoid diphtheria, tetanus Fractional vaccines *not available in the United States

25. Pure Polysaccharide Vaccines Not consistently immunogenic in children younger than 2 years of age No booster response Antibody with less functional activity Immunogenicity improved by conjugation

26. Polysaccharide Vaccines pneumococcal meningococcal Salmonella Typhi (Vi) Haemophilus influenzae type b pneumococcal meningococcal Pure polysaccharide Conjugate polysaccharide

27. Principles of Vaccination General Rule Inactivated vaccines are generally not affected by circulating antibody to the antigen. Live attenuated vaccines may be affected by circulating antibody to the antigen.

28. Product Given First Vaccine Antibody Action Wait 2 weeks before giving antibody Wait 3 months or longer before giving vaccine (See Table, Appendix A) Antibody and Measles- and Varicella-Containing Vaccines

29. Principles of Vaccination General Rule All vaccines should be administered at the same visit as all other vaccines.

30. Intervals and Ages Vaccine doses should not be administered at intervals less than the minimum intervals or earlier than the minimum age It is not necessary to restart the series or add doses because of an extended interval between doses Vaccination doesn‘t count Vaccination counts

31. Vaccine Adverse Reactions Local – pain, swelling, redness at site of injection – common with inactivated vaccines – usually mild and self-limited

32. Vaccine Adverse Reactions Systemic – fever, malaise, headache – nonspecific – may be unrelated to vaccine

33. Live Attenuated Vaccines Must replicate to produce immunity Symptoms usually mild Occur after an incubation period (usually 7-21 days)

34. Vaccine Adverse Reactions Allergic – due to vaccine or vaccine component – rare – risk minimized by screening Vaccine Adverse Event Reporting System (VAERS) www.vaers.hhs.gov

35. Contraindication A condition in a recipient that greatly increases the chance of a serious adverse reaction

36. Precaution A condition in a recipient that might increase the chance or severity of an adverse reaction, or Might compromise the ability of the vaccine to produce immunity

37. Contraindications and Precautions severe allergic reaction to a vaccine component or following a prior dose encephalopathy not due to another identifiable cause occurring within 7 days of pertussis vaccination Permanent contraindications to vaccination:

38. Vaccination of Pregnant Women Live vaccines should not be administered to women known to be pregnant In general inactivated vaccines may be administered to pregnant women for whom they are indicated

39. Vaccination of Immunosuppressed Persons Live vaccines should not be administered to severely immunosuppressed persons Inactivated vaccines are safe to use in immunosuppressed persons but the response to the vaccine may be decreased

40. Immunosuppression Disease Chemotherapy Corticosteroids

41. Invalid Contraindications to Vaccination Mild illness Antimicrobial therapy Disease exposure or convalescence Pregnant or immunosuppressed person in the household Breastfeeding Preterm birth Allergy to products not present in vaccine or allergy that is not anaphylactic Family history of adverse events Tuberculin skin testing Multiple vaccines

42. Vaccination During Acute Illness No evidence that acute illness reduces vaccine efficacy or increases vaccine adverse reactions Vaccines should be delayed until the illness has improved Mild illness, such as otitis media or an upper respiratory infection, is NOT a contraindication to vaccination