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VACCINE SAFETY

VACCINE SAFETY. Vaccine-induced feline fibrosarcoma. Current estimate is: 27,000 vaccine induced tumors expected per year ‘93 1-2 per 10,000 ‘97 3.6 per 10,000 ‘98 up to 5 per 10, 000. Pathogenesis of vaccine injection site fibrosarcomas.

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VACCINE SAFETY

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  1. VACCINE SAFETY

  2. Vaccine-induced feline fibrosarcoma • Current estimate is: 27,000 vaccine induced tumors expected per year • ‘93 1-2 per 10,000 • ‘97 3.6 per 10,000 • ‘98 up to 5 per 10, 000

  3. Pathogenesis of vaccine injection site fibrosarcomas • Injection triggers inflammation and release of platelet-derived growth factor • Activation of sis oncogene occurs • Sarcoma develops at the site

  4. Types of Adverse Responses • Vaccine injection site fibrosarcomas • Hypersensitivity Type 1 – Anaphylaxis • Hypersensitivity Type 2- Cytotoxic • Hypersensitivity Type 3 - Immune complex • Hypersensitivity Type 4 - Granulomas • Autoimmune disease • Induction of disease/ increase in severity of disease/ reversion to virulence

  5. Type I Hypersensitivity • Systemic Anaphylaxis • IgE mediated reaction • requires previous sensitization • sensitizing agent may be antigen, cross-reactive antigen, or other proteins present in vaccine • factors to consider: adjuvant, genetics

  6. Mast Cell Mechanism for type I reactions Ag Ag Smooth muscle contraction Vascular permeability Vasodilation Eosinophil Chemotaxis Histamine ECF-A Leukotrienes Mechanism for systemic anaphylaxis

  7. Induction of IgE by Vaccines • Antigen itself • virus e.g. Bovine Respiratory Syncytial Virus • bacteria e.g. Hemophilus somnus • Constituents of carrier • gelatin • Impurities in antigen preparation • fetal bovine serum, ovalbumin

  8. Examples of type I reactions to non-essential antigens • IgE responses to gelatin as a stabilizer: measles-mumps-rubella vaccine, yellow fever vaccine, diptheria-tetanus-pertussis (DTP) vaccine, and DTaP (acellular pertussis) • IgE responses to ovalbumin: yellow fever, influenza, measles, mumps

  9. More Examples • Horses vaccinated with egg-derived equine encephalitis vaccines • Cattle vaccinated with baby hamster kidney derived foot and mouth disease vaccine • Humans vaccinated with human diploid cell line rabies vaccine • Cattle vaccinated with bovine respiratory syncytial virus vaccine

  10. Type II Hypersensitivity • IgG and/or IgM binding to cell-associated antigens • Fixation of complement • Cell lysis and/or phagocytosis

  11. Host target cell Mechanism of type II Reactions Complement Lysis of target cell phagocytosis of target cell

  12. Examples of type II reactions • Immune-mediated hemolytic anemia has been associated with vaccination of dogs with combination vaccines • Hemolytic anemia and thrombocytopenia have been associated with recombinant hepatitis B vaccine in humans

  13. Type III Hypersensitivity • Immune complex diseases • IgG binds antigen fixes complement and attracts neutrophils • Systemic form: arthritis, vasculitis, glomerulonephritis • Local form: Arthus-type lesions in skin or lung

  14. Blood Vessel Mechanism of type III reactions Kidney glomeruli Joints Skin Vasculitis

  15. Examples of type III reactions • Canine Adenovirus type 1 (hepatitis) vaccine-induced “Blue eye”anterior uveitis • Local Arthus type skin reactions in all species within 24 hours of vaccine • Serum sickness-like illness in humans after immunization with human diploid cell rabies vaccine (vasculitis, arthritis)

  16. Type IV Hypersensitivity • Delayed type reaction (DTH), occurs within 48 to 72 hours after antigen administration • Mediated by sensitized T lymphocytes • Indicates strong T helper 1 cell response • Local response shows erythema, induration

  17. Mechaniam of type IV response Erythema induration 48 - 72 hours later Macrophages & T lymphocytes

  18. Examples of type IV reactions • DTH reactions have been observed in humans after immunization with propionibacterium acnes autovaccine • Children with non-anaphylactic reactions to gelatin-containing vaccine and increased lymphocyte stimulation to gelatin may have DTH reactivity

  19. Examples of Vaccines Generated Autoimmunity • Rabies vaccine-induced autoimmune encephalomyelitis • Association is suggested: for hepatitis B vaccine with rheumatoid arthritis • Auto Immune Hemolytic Anemia (AIHA) in infant girl after DPT and polio vaccination

  20. Vaccine Mediated, Enhancement of Disease • Respiratory syncytial virus formalin-inactivated vaccine caused severe RSV in vaccinated children • Bovine RSV formalin-inactivated vaccine caused disease enhancement in BRSV vaccinated calves

  21. Disease caused by vaccination • Inadequate killing resulting in residual virulence e.g. formalin inactivated Salk polio virus in late 1950’s • Immuno suppressed host, e.g. MLV in AIDS patient • Intrauterine infection of fetus after immunization of mother with MLV, e.g. teratogenic effects with bluetongue virus

  22. Summary • Adverse effects of vaccines are rare • Killed vaccines with adjuvant are more likely to have pathological sequel • Systemic anaphylaxis may result from sensitization to components of the vaccine • Immunomodulation is an important factor in disease development by vaccines

  23. Importance of Vaccine Safety • Decreased disease risks and increased attention on vaccine risks • Public confidence in vaccine safety is critical • higher standard of safety is expected of vaccines • vaccinees generally healthy (vs. ill for drugs) • vaccination universally recommended and mandated

  24. Disease Pre-vaccine Era 2005 % change Diphtheria 31,054 0 -100 Measles 390,852 66 -99 Mumps 21,342 314 -99 Pertussis 117,998 25,616 -78 Polio (wild) 4,953 0 -100 Rubella 9,941 11 -99 Cong. Rubella Synd. 19,177 1 -99 Tetanus 1,314 27 -98 Invasive Hib Disease 24,856 144 -99 Total 566,706 26,179 -95 Vaccine Adverse Events 0 15,803 +++ Comparison of Maximum and Current Reported Morbidity, Vaccine-Preventable Diseases andVaccine Adverse Events, United States

  25. Disease incidence Vaccine safety concerns

  26. Prelicensure Vaccine Safety Studies • Laboratory • Animals • Humans

  27. Prelicensure Human Studies • Phases I, II, III trials • Common reactions are identified • Vaccines are tested in thousands of persons before being licensed and allowed on the market

  28. Postlicensure Surveillance • Identify rare reactions • Monitor increases in known reactions • Identify risk factors for reactions • Identify vaccine lots with unusual rates or types of events • Identify signals

  29. Postlicensure Vaccine Safety Activities • Phase IV Trials • ~10,000 participants • better but still limited • Large-Linked Databases • Clinical Immunization Safety Assessment Network

  30. Vaccine Adverse Event Reporting System (VAERS) • National reporting system • Jointly administered by CDC and FDA • Passive (depends on healthcare providers and others to report) • Receives ~15,000 reports per year

  31. Vaccine Adverse Event Reporting System (VAERS) • Detects • new or rare events • increases in rates of known side effects • patient risk factors • Additional studies required to confirm VAERS signals • Not all reports of adverse events are causally related to vaccine

  32. Adverse Event Classification • Vaccine-induced • Vaccine-potentiated • Programmatic error • Coincidental

  33. Clinical Immunization Safety Assessment (CISA) Network • Improve understanding of vaccine safety issues at individual level • Evaluate persons who experience adverse health events • Gain better understanding of events • Develop protocols for healthcare providers

  34. Vaccine Injury Compensation Program (VICP) • Established by National Childhood Vaccine Injury Act (1986) • “No fault” program • Covers all routinely recommended childhood vaccines

  35. The Provider’s Role • Immunization providers can help to ensure the safety and efficacy of vaccines through proper: • vaccine storage and administration • timing and spacing of vaccine doses • observation of contraindications and precautions

  36. Invalid Contraindications to Vaccination • Minor illness • Mild/moderate local reaction or fever following a prior dose • Antimicrobial therapy • Disease exposure • Pregnancy or immunosuppression • Premature birth • Breastfeeding • Allergies to products not in vaccine • Family history (unrelated to immunosuppression)

  37. Benefit and Risk Communication • Opportunities for questions should be provided before each vaccination • Vaccine Information Statements (VISs) • must be provided before each dose of vaccine • public and private providers • available in multiple languages

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