1. Prof.Dr.Yıldız Camcıoğlu
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 morbidity morbidity % reduction
varicella
48164
100
Diptheria
175885 2
> 99
Pertussis
147271
7560 95
Tetanus
1314 37 97
Polio
16319
Measles
503282
116
Mumps
152209
266
Rubella
47745 23
Hib
20000
181

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)
Killed or Inactivated
Fractionated
Recombinant Live attenuated

12. Inactivated Vaccines Whole Fractional 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, typhoid cholera, 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
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 phormaldehide Tetanus, 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
Properties
Attenuated Vaccine
Inactivated Vaccine
Preparation
Virulent strain, various culture medium, long passages
Pathogen, inactivated by chemicals or gamma radiation
Booster
Just one
More than one
Stabilization
NOT GOOD
BETTER stabilized
Immune response
Humoral and cellular
Humoral

29. Adjuvant name Compositions Mechanism of action
Freund’s incomplete adjuvant
Oil-in- emulsion
Delayed release of antigen,
Enhanced uptake by macrophages
Freund’s complete adjuvant
Oil-in- water with
dead Mycobacteria
Enhanced uptake by macrophages Induction of co-stimulators in macrophages
Freund’s adjuvant
With MDP
Muramyldipeptid
Induction of co-stimulators in macrophages
Alum
Aluminum Hidroxide gel
Alum+B.pertussis
Aluminum Hidroxide gel with
Killed B.pertussis
Immun stimulatory complexes(ISCOM)
Matrix of lipid micelles containing Viral proteins
Delivers antigen to cytosol
İnduction of Cytotoxic T cells

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 2013 TURKEY
Birth
1. month
2. month
4. month
6. month
12. month
18. month
24. month
6-7
years
13-14
Hep-B
1.dose
2.dose
3.dose
BCG
(Tb vaccine)
DTaP-IPV-Hib -
4.dose
Pneumococcal
Conjugated
Vaccine (PCV)
MMR
DTaP-IPV
Oral Polio vaccine(OPV)
Td(Tetanus,
adult dose diphteria
Hep-A
Varicella

32. DTaP-IPV-Hib: Diphtheria/Tetanus Toxoids/Acellular Pertussis/Inactivated Polio Vaccine (Diphteria, acellular Pertussis, Tetanus, Inactivated Polio vaccine, Hemofilus influenzae type b vaccine PCV: Pneumococcal Conjugated Vaccine MMR :Measles, Mumps, Rubella DTaP-IPA: Diphtheria/Tetanus Toxoids/Acellular Pertussis/Inactivated Polio Vaccine
OPA: Oral Polio Vaccine Td:Tetanus and adult type diphteria B: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. >6 years 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
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 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 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 months and 4-6 years
IPV at 2, 4, 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 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.