Transcript Vaccines

Prof.Dr.Yıldız Camcıoğlu
İÜ.Cerahpaşa Tıp Fakültesi
Çocuk Sağlığı ve Hastalıkları ABD
Enfeksiyon Hastalıkları, Klinik İmmünoloji ve
Allerji Bilim Dalı
Principles of Vaccination
Immunity
• Protection from infectious disease
• Usually indicated by the presence of antibody
• Very specific to a single antigen
1990-2001 Infectious Diseases(CDC)
illness
varicella
Diptheria
Pertussis
Tetanus
Polio
Measles
Mumps
Rubella
Hib
1990-99 morbidity
48164
175885
147271
1314
16319
503282
152209
47745
20000
2001 morbidity
0
2
7560
37
0
116
266
23
181
% reduction
100
> 99
95
97
100
> 99
> 99
> 99
> 99
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)
Principles of Vaccination
Active Immunity
• Protection produced by the person's own immune
system
• Usually permanent
Passive Immunity
• Protection transferred from another person or
animal as antibody
• Temporary protection that wanes with time
A2
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)
Antibody
• Protein molecules (immunoglobulin) produced by B
lymphocytes to help eliminate an antigen
Passive Immunity
• Transfer of antibody produced by one
human or other animal to another
• Transplacental most important source in
infancy
• Temporary protection
Sources of Passive Immunity
• Almost all blood or blood products
• Homologous pooled human antibody
(immune globulin)
• Homologous human hyperimmune globulin
• Heterologous hyperimmune serum
(antitoxin)
Vaccination
• Active immunity produced by vaccine
• Immunity and immunologic memory similar
to natural infection but without risk of
disease
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
Classification of Vaccines
Currently available vaccines are
either:
• Live (attenuated)
• Killed or Inactivated
• Fractionated
• Recombinant Live attenuated
Inactivated Vaccines
Whole
• virus
• bacteria
Fractional
• protein-based
– subunit
– toxoid
• polysaccharide-based
– pure
– conjugate
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
Live Attenuated Vaccines
• Severe reactions possible
• Interference from circulating antibody
• Unstable
Live Attenuated Vaccines
• Viral
• Bacterial
measles, mumps,
rubella, vaccinia,
varicella, yellow fever,
influenza, (oral polio)
(rotavirus)
BCG, oral typhoid
Vaccines in (parenthesis) are not available in the United States.
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
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.
Inactivated Vaccines
Fractional vaccines
• Subunit
hepatitis B, influenza,
acellular pertussis, Lyme
•
• Toxoid
diphtheria, tetanus
Polysaccharide Vaccines
Pure polysaccharide
• pneumococcal
• meningococcal
• Salmonella Typhi (Vi)
Conjugate polysaccharide
• Haemophilus influenzae type b
• pneumococcal
Pure Polysaccharide Vaccines
• Not consistently immunogenic in children
<2 years of age
• No booster response
• Antibody with less functional activity
• Immunogenicity improved by conjugation
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.
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.
Content of Vaccines
•
•
•
•
Component
Prezervatives
Stabilizers
Antibiotics
Adjuvants
• Suspending fluids
Functions
Prevent bacterial growth
Stabilize the antigen
Neomycin, Streptomycin
Enhances immunogenecity
Aluminum hydroxide
Sterile water or saline
Complex fluids (egg yolk antigen,
substances in tissue culture,
serum proteins)
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)
Vaccines 1
• Attenuated Vaccines;
• Viral : Polio (Sabin), Measles, Rubella, Mumps,
Varicella, Rotavirus, Sarı humma
Bacterial; BCG
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
Recombinant(syntetic)
vaccine
• Hepatitis B surface antigen gene
• Produce in Maya cells
• Purification of recombinant strain
• Immune response
Attenuated and inactivated vaccine
Properties
Attenuated Vaccine Inactivated Vaccine
Preparation
Booster
Virulent strain,
various culture
medium, long
passages
Just one
Pathogen,
inactivated by
chemicals or
gamma radiation
More than one
Stabilization
NOT GOOD
BETTER stabilized
Immune response
Humoral and
cellular
Humoral
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
Delayed release of antigen,
Enhanced uptake by macrophages
Induction of co-stimulators in
macrophages
Freund’s adjuvant
With MDP
Oil-in- water with
Muramyldipeptid
Delayed release of antigen,
Enhanced uptake by macrophages
Induction of co-stimulators in
macrophages
Alum
Aluminum Hidroxide
gel
Delayed release of antigen,
Enhanced uptake by macrophages
Alum+B.pertussis
Aluminum Hidroxide
gel with
Killed B.pertussis
Delayed release of antigen,
Enhanced uptake by macrophages
Induction of co-stimulators in
macrophages
Immun stimulatory
complexes(ISCOM)
Matrix of lipid micelles
Delivers antigen to cytosol
containing Viral proteins İnduction of Cytotoxic T cells
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)
Ministry of Health-Immunization Schedule 2013
TURKEY
Hep-B
BCG
(Tb vaccine)
DTaP-IPV-Hib
Pneumococcal
Conjugated
Vaccine (PCV)
MMR
DTaP-IPV
Oral Polio
vaccine(OPV)
Td(Tetanus,
adult dose
diphteria
Hep-A
Varicella
Birth
1.
2.
4.
6.
12.
18.
24.
6-7
month month month month month month month years
1.dose
2.dose
13-14
years
3.dose
1.dose
-
1.dose
2.dose 3.dose
4.dose
1.dose 2.dose 3.dose 4.dose
1.dose
1.dose
2.dose
1.dose
2.dose
1.dose
1.dose 2.dose
1.dose
• 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
Advisory Committee on Immunization Practices (ACIP) Recommended
Immunization Schedule for Persons Aged 0 Through 18 Years —
United States, 2013
<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
>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
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)
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
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.
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
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
• 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.
• 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.