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Milestones in immunizationMilestones in immunization

1500BC Turks introduce

variolation

3000BC Evidence of sniffing

powdered small pox crust in Egypt

2000BC Sniffing of small

pox crust in China

1700AD Introduction of

variolation in England and later in the US

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The wife of the British Ambassador in Turkey, in March 1717 wrote, followingthe variolation of her son, to a friend inEngland: “The small pox, so fatal, so general amongst us, is entirely harmless here by the invention of ingrafting….I am patriot enough to bring this invention into fashion in England.

The wife of the British Ambassador in Turkey, in March 1717 wrote, followingthe variolation of her son, to a friend inEngland: “The small pox, so fatal, so general amongst us, is entirely harmless here by the invention of ingrafting….I am patriot enough to bring this invention into fashion in England.

Introduction of variolationIntroduction of variolation

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Milestones in immunizationMilestones in immunization

1780AD Edward Jenner discovers

small pox vaccine

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Edward Jenner

Discovery of small pox vaccine

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Edward JennerAmong patients awaiting small pox vaccination

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1920sDiphtheria and Tetanus

1934Pertussis

1955Salk polio

Modern era of the vaccineModern era of the vaccine

1885Rabies vaccine (Pasteur)

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1960sMumps measles and rubella virus

Sabin polio

1990s

Hepatitis and varicella

1985

Haemophilus

Modern era of the vaccineModern era of the vaccine

2000Human Papillomavirus(HPV)

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Pre- & post-vaccine incidence of common preventable diseases

Pre- & post-vaccine incidence of common preventable diseases

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Different modes of acquiring immunity

Different modes of acquiring immunity

Natural resistance

Artificial Natural

Passive

Artificial Natural

Active

Immunity

Acquired

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Natural Artificial

Colostral transfer of IgA

Placental transfer of IgG

Antibodies or immunoglobulins

Immune cells

Passive ImmunityPassive Immunity

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 disease  indicationantibody source

Passive ImmunizationPassive Immunization

human, horsediphtheria, tetanus prophylaxis, therapy

vericella zoster human immunodeficiencies

gas gangrene, botulism, snake bite, scorpion sting

horse post-exposure

rabies, human post-exposure

hypogamma-globulinemia

human prophylaxis

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Advantages Disadvantages

serum sicknessimmediate protection

no long term protection

graft vs. host disease (cell graft only)

risk of hepatitis and Aids

Advantages and Disadvantages of Passive Immunization

Advantages and Disadvantages of Passive Immunization

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Active ImmunizationActive Immunization

Natural Artificial

exposure to sub-clinical infections

Attenuated organisms

killed organisms

sub-cellular fragments

toxins

others

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tuberculosisnot used in this country

polio*not used in std. schedule

measles, mumps & rubella

yellow feverMilitary and travelers

Varicella zosterchildren with no history of chicken pox

hepatitis Astandard 2006

Live Attenuated VaccinesLive Attenuated Vaccines

Influenza selected age group (5-49)

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polio

influenzaelderly and at risk

typhoid, cholera, plagueepidemics and travelers

rabiespost exposure

pertussis replaced by the acellular vaccine

Killed Whole-Organism VaccinesKilled Whole-Organism Vaccines

Q feverpopulation at risk

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Microbial Fragment VaccinesMicrobial Fragment Vaccines

Bordetella. Pertussisvirulence factor protein

Haemophilus influenzae Bprotein conjugated polysaccharide

Streptococcus pneumoniaePolysaccharide mixture

Neisseria meningitidispolysaccharide

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Microbial Fragment VaccinesMicrobial Fragment Vaccines

Clostridium tetani (tetanus)inactivated toxin (toxoid)

Corynebacterium diphtheriaeinactivated toxin (toxoid)

Vibrio choleraetoxin subunits

Hepatitis B viruscloned in yeast

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Modification of Toxin to ToxoidModification of Toxin to Toxoid

toxin moiety antigenic determinants

chemical

modification

Toxin Toxoid

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anti-Idiotype Vaccine

Immuno-dominant peptide

Future VaccinesFuture Vaccines

DNA

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anti-Idiotype Vaccine

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Antiidiotype antibody in tolerance

Antiidiotype antibody production

Antiidiotype mediated tolerance

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AdjuvantsAdjuvants

• Salts:• Al(OH)3; AlPO4;

CaPO4• Be(OH)2

YesYesNo

Human use Mode of action

Slow release of antigen; TLR interaction and cytokine induction

Adjuvant type

Slow release of antigenNo• Mineral oils without

bacteria

Yes• Bacteria in Mineral oils (Mycobacteria, Nocardia) No

Slow release of antigen TLR interaction and cytokine induction

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AdjuvantsAdjuvants

Human use Mode of actionAdjuvant type

• Synthetic polymers:• Liposomes• ISCOM• Poly-lactate

Slow release of antigenNo

Yes• Bacteria:

• Bordetella pertussis• Mycobacterium bovis

(BCG and others)No

TLR interaction and cytokine induction

• Bacterial products:• Myramyl peptides No

TLR interaction and cytokine induction

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AdjuvantsAdjuvants

• Poly-nucleotides:• CpG No*

Human use Mode of action

TLR interaction and cytokine induction

Adjuvant type

• Cytokines:• IL-1, IL-2, IL-12,

IFN-γ, etc. No*Activation of T and B cells and APC

*Used in experimental immunotherapy of human malignancies

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Recommended Childhood Immunization Schedule

MMWR, 55: Jan 5, 2007

Recommended age range Catch-up immunization Certainigh risk groups

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Recommended Immunization Schedule for Ages 7-18

MMWR, 55: Jan 5, 2007

Recommended age range Catch-up immunization Certainigh risk groups

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Adverse Events OccurringWithin 48 Hours DTP of Vaccination

Adverse Events OccurringWithin 48 Hours DTP of Vaccination

 Event  Frequencylocalredness, swelling, pain 1 in 2-3 doses

systemic: Mild/moderatefever, drowsiness, fretfulness vomiting anorexia

1 in 2-3 doses

1 in 5-15 doses

systemic: more serious persistent crying, fevercollapse, convulsionsacute encephalopathypermanent neurological deficit

1 in 100-300 doses1 in 1750 doses1 in 100,000 doses1 in 300,000 doses