Abdul Ghaffar Microbiology and Immunology
Milestones in immunization
u3000BC
u
u1500BC
u
Evidence of sniffing powdered small pox crust in Egypt
Turks introduce variolation
u2000BC
u
u1700AD
u Introduction
Sniffing of small pox crust in China
of variolation in England and later in the US
2
Introduction of variolation
The wife of the British Ambassador in Turkey, in March 1717 wrote, following the variolation of her son, to a friend in England: “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.
3
Milestones in immunization
u1780AD
u
Edward Jenner discovers small pox vaccine
4
Edward Jenner
Discovery of small pox vaccine
5
Edward Jenner
Among patients awaiting small pox vaccination
6
Modern era of the vaccine
1885
Rabies vaccine (Pasteur)
1934
Pertussis
1920s
Diphtheria and Tetanus
1955
Salk polio
7
Modern era of the vaccine
1960s
Mumps measles and rubella virus Sabin polio
1985
Haemophilus
1990s
Hepatitis and varicella
8
Pre- & post-vaccine incidence of common preventable diseases
9
Different modes of acquiring immunity
Immunity
Natural Acquired resistance
Passive Active
Artificial Natural Artificial Natural
10
Passive Immunity
Natura l
Placental transfer of IgG Colostral transfer of IgA
Artificia l
Antibodies or immunoglobulins Immune cells
11
Passive Immunization
disease
diphtheria, tetanus vericella zoster
gas gangrene, botulism, snake bite, scorpion sting
antibody source
human, horse human horse human human
indication
prophylaxis, therapy immunodeficiencies post-exposure post-exposure prophylaxis
12
rabies,
hypogammaglobulinemia
Advantages and Disadvantages of Passive Immunization
Advantages
Disadvantages
no long term protection
immediate protection
serum sickness risk of hepatitis and Aids graft vs. host disease (cell graft only)
13
Active Immunization
Natural
Artificial
Attenuated organisms
killed organisms
exposure to subclinical infections sub-cellular fragments toxins others
14
Live Attenuated Vaccines
polio*
measles, mumps & rubella Varicella zoster
children with no history of chicken pox not used in std. schedule
hepatitis A
standard 2006
yellow fever
Military and travelers
Influenza
selected age group
(5-49)
tuberculosis
not used in this country
15
Killed Whole-Organism Vaccines
polio
Q fever
population at risk
influenza
elderly and at risk
typhoid, cholera, plague
epidemics and travelers
rabies
post exposure
pertussis
replaced by the acellular vaccine
16
Microbial Fragment Vaccines
Bordetella. Pertussis
virulence factor protein
Haemophilus influenzae B
protein conjugated polysaccharide
Streptococcus pneumoniae
Polysaccharide mixture
Neisseria meningitidis
polysaccharide
17
Microbial Fragment Vaccines
Clostridium tetani (tetanus)
inactivated toxin (toxoid)
Corynebacterium diphtheriae
inactivated toxin (toxoid)
Vibrio cholerae
toxin subunits
Hepatitis B virus
cloned in yeast
18
Modification of Toxin to Toxoid
Toxin
chemical modification
Toxoid
toxin moiety
antigenic determinants
19
Future Vaccines
anti-Idiotype Vaccine
DNA
Immuno-dominant peptide
20
anti-Idiotype Vaccine
21
Antiidiotype antibody in tolerance
Antiidiotype antibody production Antiidiotype mediated tolerance
22
Adjuvants
Adjuvant type Human use Mode of action Slow release of antigen; TLR interaction and cytokine induction
• Salts: • Al(OH)3; AlPO4; CaPO4 • Be(OH)2
• Mineral oils without bacteria • Bacteria in Mineral oils (Mycobacteria, Nocardia)
Yes Yes No No
Yes No
Slow release of antigen
Slow release of antigen TLR interaction and cytokine induction
23
Adjuvants
Adjuvant type Human use Yes No Mode of action
• Bacteria:
• Bordetella pertussis • Mycobacterium bovis (BCG and others)
TLR interaction and cytokine induction
TLR interaction and cytokine induction
• Bacterial products:
• Myramyl peptides
No
• Synthetic polymers: • Liposomes • ISCOM • Poly-lactate
No
Slow release of antigen
24
Adjuvants
Adjuvant type Human use Mode of action TLR interaction and cytokine induction Activation of T and B cells and APC
• Poly-nucleotides: • CpG
• Cytokines: • IL-1, IL-2, IL-12, IFN-γ, etc.
No*
No*
*Used in experimental immunotherapy of human malignancies
25
Recommended Childhood Immunization Schedule
Recommended age range
Catch-up immunization
Certainigh risk groups
MMWR, 55: Jan 5, 2007 26
Recommended Immunization Schedule for Ages 7-18
Recommended age range
Catch-up immunization
Certainigh risk groups
MMWR, 55: Jan 5, 2007 27
Adverse Events Occurring Within 48 Hours DTP of Vaccination
Event
local
redness, swelling, pain 1 in 2-3 doses 1 in 2-3 doses 1 in 5-15 doses 1 in 100-300 doses 1 in 1750 doses 1 in 100,000 doses 1 in 300,000 doses
29
Frequency
systemic: Mild/moderate
fever, drowsiness, fretfulness vomiting anorexia
systemic: more serious
persistent crying, fever collapse, convulsions acute encephalopathy permanent neurological deficit