Transcript VACCINE IMMUNOLOGY

Vaccination vs. Immunisation
Vaccination is the term used forgiving a vaccine - that is the
process of introducing a substance to a host (i.e. Injection or
droplets).
Immunisation is the term used for the process of both getting
the vaccine and becoming immune to the disease as a result of
the vaccine.
• Vaccination – named from the use of vaccinia, or
cowpox, to induce immunity to variola (smallpox)
in humans.
Early history of vaccination
• 7th Century - Indian Buddhists drank snake venom
(for snakebites).
• 10th/17th Century China – “inoculation or
variolation” (for smallpox).
• Variolation (inoculation)- introduced to Europe
from Turkey in 1721.
History of vaccination
Lady Mary Montague, who witnessed variolation in
Istanbul, came back UK and had her daughter
inoculated. She then advised the royal family to
have their children inoculated .
As a safeguard, the procedure was first tested on six prisoners
(death penalty). All survived and pardoned. Royal children
inoculated and survived and variolation became fashionable in
Europe.
Edward Jenner
History of vaccination
14 May 1796
Edward Jenner used material from a cowpox
pustule on the hand of Sarah Nelmes to
vaccinate James Phipps (8 yr boy).
1 July 1796
Jenner used virulent smallpox matter to
challenge James Phipps.
Experiment successful: Phipps survived many
subsequent exposure over 20 yrs
Smallpox vaccination
• 300 million people died of smallpox in the
first three-quarter of the 20th Century.
• Smallpox eradicated in 1979 because of
mass vaccination programme
Goals of vaccination
• In individuals - prevention of disease
• In populations - eradication of disease
Immunisation Schedule in
Saudi arabia
*BCG (Bacillus Calmette-Guérin) is the current vaccine against TB.
Vaccination saves lives
Infant vaccination
programmes have saved
approx. 3 million deaths
worldwide annually
Hepatitis B (900,000),
measles (900,000),
tetanus (400,000),
H. influenzae (400,000),
pertussis (350,000),
yellow fever (30,000),
diphtheria (5,000)
polio (800)
Major diseases that could be prevented by no
effective vaccines yet
Types of immunisation
1. Active
Administration of antigen (modified
infectious agent or toxin) resulting in
active production of immunity eg.
antibodies
2. Passive
Administration of antibody-containing
serum or sensitised cells
Active
• natural (unintended)
• deliberate - vaccination
Passive
• Placental transfer (IgG)
• colostral transfer (IgA)
• transfer of human Ig or cells
A good vaccine should be:
• Safe - no significant side effects
• Effective, and preferably long-lasting
• Stable in storage
• Cost-effective for the target population
Types of vaccines
1. Live attenuated vaccines
2. Inactivated vaccines (killed)
3. Subunit vaccines
Types of vaccines
Live attenuated
Measles, mumps, rubella, polio, BCG (TB)
Inactivated
Heat killed organisms  typhoid, cholera, pertussis
Toxoid  (inactive form of toxin, capable of inducing Ab
to toxin which causes disease). eg. Diptheria, tetanus
Types of vaccines
Subunit
• Polysaccharide (PS), conjugate PS
eg. Pneumococcal PS, meningococcal PS
• Recombinant DNA products / purified
proteins
eg. hepatitis B, influenza proteins
Live vaccines
Advantages
• single, small dose
• given by natural route
• local & systemic immunity
• resembles natural infection
Disadvantages
• contaminating virus,
• reversion to virulence
• inactivation by climatic changes
Inactivated (killed) vaccines
Advantages
• safe
• stable, so for each batch the safety and
efficiency is known
Disadvantages
• multiple doses and boosters needed
• given by injection - unnatural route
• high antigen concentration needed
• variable efficiency
Polio Vaccines as a example
• 1958, killed (inactivated) virus ‘Salk’ vaccine
introduced, but cannot replicate in cytosol to produce
‘endogenous’ peptides for presentation to CD8+ T cells
• 1962, Switched to oral live attenuated virus
‘Sabin’ (OPV) , more potent, but can rarely revert
back to a virulent strain causing vaccine associated
paralytic polio (VAPP).
• 2004, changed to inactivated polio vaccine
Safety
Live
vaccines
Killed
vaccines
Immunogenicity
Single
proteins
Principles of Vaccination
• To induce a primary response without direct
exposure to the infective pathogen
• To induce immune memory so that a more rapid
and efficient protective response are induced if
the original pathogen is ever encountered again
Vaccination - like a minor infection at an
epithelial surface
Antibody
Tc-dependent M activation
Cytotoxic T cells
T cell-mediated immunity
Function of Antibody -1
Function of Antibody -2
Opsonisation
IgG1, IgG3, IgG4, IgA
Function of Antibody -3
Antibody-dependent cellular cytotoxicity(ADCC)
IgG1, IgG3
Function of Antibody -4
-Activation of the complement cascade
IgG
IgA
IgM
The affinity as well as
the amount of
antibody increases with
repeated immunization
© 2001 by Garland Science
Primary vs Memory response
Adjuvant
immunogen
+
adjuvant
=
enhanced
response
• To hold the antigen and release it slowly
• local inflammation, attract immune cells, eg. APC
• enhance Ag uptake, processing and presentation by APC
• promoting local cytokine production
Adjuvants
• Alum. hydroxide suspension
• Pertussis toxin - mixed with Diphtheria and
Tetanus toxoid  DTP triple vaccine
Polysaccharide vaccines
Encapsulated
bacteria
Against Hib, menigococcus,
pneumococcus.
Capsular PS, virulence factor
Immune response to PS vaccines
Limitations of polysaccharide vaccines
1. T cell independent antigen:
• Stimulate B cell for antibody production
without T-cell help
2. Poorly immunogenic in infancy
(Not effective in young children)
3. No memory
But Effective in older children and adults
Making PS Ag T-cell dependent
- conjugate vaccines

PS conjugated to a carrier protein to create a “T
cell antigen”
Tetanus toxoid
polysaccharide
• T-cells recognise the protein (eg. TT) and activated
• Activated T cells provide signals (eg cytokines) to
‘help’ B-cells to produce antibodies
Conjugate polysaccharide vaccines
Protein Ag attached to PS allow T cells to help
PS-specific B cells.
© 2001 by Garland Science
Conjugate polysaccharide vaccines
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© 2001 by Garland Science
Immune response to
Conjugate PS vaccines
Advantages of conjugate vaccines
• More immunogenic than PS vaccines
• Effective in young children as well
• T cell involvement and Immunological memory
• Long-term protection
Limitation of conjugate vaccines

Limited serotype coverage

Increase in non-vaccine serotypes after
vaccination

expensive
Herd Immunity
• Unimmunised individuals are also protected against
a disease as well as most others immunised in the
community.
• Herd immunity needs substantial coverage of
population by vaccination.
• If substantial portion of community not immune
then introduced virus can circulate and cause disease
in nonimmune group.
Passive Immunisation
• Provide antibodies - whole serum or
immunoglobulin (mainly IgG).
• Provide immediate protection, eg rabies,
tetanus, diphtheira.
• No long term protection.
Haemolytic disease in the newborn
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RhD- mother with RhD+ fetus can develop anti-Rh
antibodies and cause haemolysis to the newborn and
subsequent pregnancy.
Antenatal and postnatal administration of antiRhD immunoglobuin to RhD- mother can prevent
haemolysis in the newborns
Immunity
Innate
Acuired
Passive
Artificial
Natural
Active
Artificial
Natural
The end