Prof.Dr.Yıldız Camcıoğlu İÜ.Cerahpaşa Tıp Fakültesi Çocuk Sağlığı ve Hastalıkları ABD

1. Principles of Vaccination Prof.Dr.Yıldız Camcıoğlu İÜ.Cerahpaşa Tıp Fakültesi Çocuk Sağlığı ve Hastalıkları ABD Enfeksiyon Hastalıkları, Klinik İmmünoloji ve Allerji Bilim Dalı

2. Principles of Vaccination Immunity • Protection from infectious disease • Usually indicated by the presence of antibody • Very specific to a single antigen

3. 1990-2001 Infectious Diseases(CDC) illness 1990-99 morbidity 2001 morbidity % reduction

4. What is Vaccine  ? • Vaccinations are supposed to confer immunity • Standard manufacture uses a bacterial or viral antigen • Bacterium or virus, which may be killed, generally with formol or heat may be living but attenuated. • Bacterial vaccines can contain All of the bacterium (killed by heat ;whooping-cough vaccine)or can be acellular (only antigenic fragments). • Diphtheria and tetanus vaccines are “anatoxins”; they contain only the toxin (attenuated) produced by the bacteria and supposed to be responsible for the disease • The attenuation by rapid passage in a culture (BCG by 230 passages in potatoes mixed with beef bile; or measles by 85 passages in chicken fibroblasts)

5. Principles of Vaccination Active Immunity • Protection produced by the person's own immune system • Usually permanent • Protection transferred from another person or animal as antibody • Temporary protection that wanes with time Passive Immunity A2

6. Principles of Vaccination Antigen • A live or inactivated substance capable of producing an immune response Single constituent,e.g.,, polysaccharide or tetanus, diphteria) Complex constituent(live viruses , killed pertusssis bacteria) • Protein molecules (immunoglobulin) produced by B lymphocytes to help eliminate an antigen Antibody

7. Passive Immunity • Transfer of antibody produced by one human or other animal to another • Transplacental most important source in infancy • Temporary protection

8. Sources of Passive Immunity • Almost all blood or blood products • Homologous pooled human antibody (immune globulin) • Homologous human hyperimmune globulin • Heterologous hyperimmune serum (antitoxin)

9. Vaccination • Active immunity produced by vaccine • Immunity and immunologic memory similar to natural infection but without risk of disease

10. Vaccines Effective vaccines are: • Safe • Protective for sustained period • Induce neutralising antibody • In addition they should be: • Biologically stable • Cheap to produce • Easy to administer

11. Classification of Vaccines Currently available vaccines are either: • Live (attenuated) • Killedor Inactivated • Fractionated • Recombinant Live attenuated

12. Inactivated Vaccines Whole • virus • bacteria • protein-based • subunit • toxoid • polysaccharide-based • pure • conjugate Fractional

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

14. Live Attenuated Vaccines • Severe reactions possible • Interference from circulating antibody • Unstable

15. Live Attenuated Vaccines • Viral measles, mumps, rubella, vaccinia, varicella, yellow fever, influenza, (oral polio) (rotavirus) • Bacterial BCG, oral typhoid Vaccines in (parenthesis) are not available in the United States.

16. Inactivated Vaccines • Cannot replicate • Minimal interference from circulating antibody • Generally not as effective as live vaccines • Generally require 3-5 doses • Immune response mostly humoral • Antibody titer diminishes with time

17. Inactivated Vaccines Whole cell vaccines • Viral polio, hepatitis A, rabies, influenza • Bacterial pertussis, typhoidcholera, plague Vaccines in (parenthesis) are not available in the United States.

18. Inactivated Vaccines Fractional vaccines • Subunit hepatitis B, influenza, acellular pertussis,Lyme • Toxoid diphtheria, tetanus

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

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

21. Immunological Principles of Vaccination • Vaccination is intended to provide long-term protection after its administration • Effector T- and B-cells last only a few days, so the prime requisite of any vaccine is to generate immunological memory.

22. Successful Vaccines • Activate antigen-presenting cells to initiate antigen processing and produce cytokines • Activate both T and B cells to give a high yield of memory cells • Generate Th and Tc cells to several epitopes, to overcome the variation in the immune response in the population due to MHC polymorphism • Enable the persistence of antigen, probably on follicular dendritic cells in lymphoid tissue, to elicit continued production of antibody from B cells. • Whole organism vaccines tend to have these abilities. Subunit vaccines can be enhanced to produce these results by the use of adjuvants, such as alum.

23. Content of Vaccines Component Functions • Prezervatives Prevent bacterial growth • Stabilizers Stabilize the antigen • Antibiotics Neomycin, Streptomycin • Adjuvants Enhances immunogenecity Aluminum hydroxide • Suspending fluids Sterile water or saline Complex fluids (egg yolk antigen, substances in tissue culture, serum proteins)

24. Preservatives • Tiomersal ; DT, dT, TT, İnfluenzae Pneumococcal polysaccharide(Wyett) • 2-phenoxietanol ve formaldehide; IPV • Phenol Tifo Vi, Pneumococcal polysaccharide (pasteur) • Benzetonium chlorur(femerol); Şarbon • 2-phenoxyetanol; DBaT (Infanrix, GSK) Hepatitis A (Havrix, GSK) Hepatitis A/B(Twinrix, GSK) Lyme (Lymerix, GSK)

25. Vaccines 1 • Attenuated Vaccines; • Viral : Polio (Sabin), Measles, Rubella, Mumps, Varicella, Rotavirus, Sarı humma Bacterial; BCG

26. Vaccines 2 • Toxoid:Exotoxin inactivated by phormaldehideTetanus, Diphteria • Subunite vaccines: Influenzae, Hepatitis B, Acellular pertussis • Inactivated whole cell :inactiveted by phormaldehide Polio (Salk), Influenzae , Rabies, Hepatitis A, Pertussis, Typhi, Cholera, Plaque • Pure polysaccharide(TI); S.pneumoniae N.Meningitidis • Conjugated-polysaccharide;TD antigen;Hib,S.pneumoniae Polysaccharides proteins conjugated Tetanus, OMP, Diphteria

27. Recombinant(syntetic)vaccine • Hepatitis B surface antigen gene • Produce in Maya cells • Purification of recombinant strain • Immune response

28. Attenuated and inactivated vaccine

30. T Independent antigens: ( TI) TI-1 E.coli LPS TI-2 Pneumoccus polysaccaride H.influenza tip b (Hib-prp) Meningococcus polysaccaride T Dependent antigens: (TD) • Tetanus toxoid • Dipheriae toxoid • Influenzae vaccine • Inactive polio vaccine(Salk)

31. Ministry of Health-Immunization Schedule 2013TURKEY

32. DTaP-IPV-Hib: Diphtheria/TetanusToxoids/AcellularPertussis/InactivatedPolioVaccine (Diphteria, acellularPertussis, Tetanus, InactivatedPoliovaccine, Hemofilusinfluenzaetype b vaccinePCV: PneumococcalConjugatedVaccineMMR :Measles, Mumps, RubellaDTaP-IPA: Diphtheria/TetanusToxoids/AcellularPertussis/InactivatedPolioVaccine • OPA: Oral PolioVaccineTd:TetanusandadulttypediphteriaB:Booster

33. Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedule for Persons Aged 0 Through 18 Years — United States, 2013

34. <6 years of age, Never vaccinated previously • First day DaBT-IPA-Hib,Hep B1, PPD • 2 days later MMR1, BCG • 2 months later DaBT-IPA-Hib, * • At least 8 months later DaBT-IPA-Hib, Hep B3, OPA

35. >6years of age, Never vaccinated previously • First Day; Td1, OPA1, Hep B1, MMR • 1 month later Td2, OPA2, Hep B2, MMR • At least 8 months later Td3, OPA3, Hep B3

36. Vaccination at School • At class 6 OPA-3, MMR-Booster, Td-1 • At class 8 Td-2 Rubella (Vaccine introduced in 2007, Born children in 2007 are not vaccinated.They are the cohort to be vaccinated) Hepatitis B; 3 doses, at intervals 0-1-4 (Vaccine introduced in 1998 , Born children in 1998 are not vaccinated, They are the cohort to be vaccinated)

37. Vaccination scheduled for Adolecent Hepatitis B; No vaccination previously 0,1, 6 MMR; 2 doses before 12 years of age, once who has not vaccinated previosly Varicella; Once for 11-12 years of age 2 doses, 1-2 months interval, after 13 years of age Meningoccoccus; Once for the adolecents at high risksuch as dormitories Hepatitis A; 0 and 6 HPV ; 0, 2, 6

38. Catch-up vaccination in USA • Persons aged 7 through 10 years who are not fully immunized with the childhood DTaP vaccine series, should receive Tdap vaccine as the first dose in the catch-up series; if additional doses are needed, use Td vaccine. For these children, an adolescent Tdap vaccine should not be given. • Persons aged 11 through 18 years who have not received Tdap vaccine should receive a dose followed by tetanus and diphtheria toxoids (Td) booster doses every 10 years thereafter. • An inadvertent dose of DTaP vaccine administered to children aged 7 through 10 years can count as part of the catch-up series. This dose can count as the adolescent Tdap dose, or the child can later receive a Tdap booster dose at age 11–12 years.

39. These children should not get vaccines • People with minor illnesses, such as a cold, may be vaccinated • These people should wait: Anyone who is moderately or severely ill at the time the shot is scheduled should usually wait until they recover before getting vaccine • Primary or secondary immunodeficiencies • Any one who had a severe unexpected or allergic reaction to a vaccine should not get another one • Anyone who has ever had a life-threatening allergic reaction to the antibiotics: neomycin, streptomycin or polymyxin B or Egg should NOT get the vaccine • Pregnancy, avoid with live vaccines

40. Schedule for Routine Immunizations • Advisory Committee on Immunization Practices (ACIP), American Academy of Pediatrics (AAP), American Academy of Family Physicians (AAFP) • Infants born to HBsAg-negative mothers should receive 2.5 µg of Merck vaccine (Recombivax HBÆ ) or 10 µg of SmithKlineBeecham (SB) vaccine (Engerix-BÆ ) The 2nd dose should be administered greater than or equal to one month after the 1st dose. • Infants born to HBsAg-positive mothers should receive 0.5 mL hepatitis B immune globulin (HBIG) within 12 hrs of birth and either 5µg of Merck vaccine (Recombivax HBÆ ) or 10 µg of SB vaccine (Engerix-BÆ ) at a separate site. The 2nd dose is recommended at 1-2 months of age and the 3rd dose at 6 months of age

41. DTaP (diphtheria and tetanus toxoids and acellular pertussis vaccine) is the preferred vaccine or equal to 1 dose of whole-cell DTP vaccine. • Td (tetanus and diphtheria toxoids, adsorbed, for adult use) is recommended at 11-12 yrs of age if at least 5 years have elapsed since the last dose of DTP, DTaP, or DT. Subsequent routine Td boosters are recommended every 10 years. • H. influenzae type b (Hib) conjugate vaccines are licensed for infant use.

42. Two poliovirus vaccines are currently licensed; inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV). • IPV at 2 and 4 mos; OPV at 12-18 months and 4-6 years • IPV at 2, 4, 12-18 months, and 4-6 years • OPV at 2, 4, 6-18 months, and 4-6 years • IPV is the only poliovirus vaccine recommended for immunocompromised persons and their household contacts • The first dose of MMR at 12 months of age The 2nd dose of MMR at 4-6 or at 11-12 years of age • Susceptible children may receive Varicella vaccine (Var) after the 1st birthday. Susceptible persons 13 years of age or older should receive 2 doses at least 1 month apart.