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VACCINE IMMUNOLOGY
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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.
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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
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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.
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Edward Jenner
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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
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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
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Goals of vaccination In individuals - prevention of disease
In populations - eradication of disease
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Immunisation Schedule in Saudi arabia
*BCG (Bacillus Calmette-Guérin) is the current vaccine against TB.
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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)
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Major diseases that could be prevented by no effective vaccines yet
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Types of immunisation Active Passive
Administration of antigen (modified infectious agent or toxin) resulting in active production of immunity eg. antibodies Passive Administration of antibody-containing serum or sensitised cells
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Active Passive natural (unintended) deliberate - vaccination
Placental transfer (IgG) colostral transfer (IgA) transfer of human Ig or cells
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A good vaccine should be:
Safe - no significant side effects Effective, and preferably long-lasting Stable in storage Cost-effective for the target population
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Types of vaccines Live attenuated vaccines
Inactivated vaccines (killed) Subunit vaccines
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Types of vaccines Live attenuated Inactivated
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
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Types of vaccines Subunit Polysaccharide (PS), conjugate PS
eg. Pneumococcal PS, meningococcal PS Recombinant DNA products / purified proteins eg. hepatitis B, influenza proteins
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Live vaccines Advantages single, small dose given by natural route
local & systemic immunity resembles natural infection Advantages contaminating virus, reversion to virulence inactivation by climatic changes Disadvantages
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Inactivated (killed) vaccines
Advantages safe stable, so for each batch the safety and efficiency is known multiple doses and boosters needed given by injection - unnatural route high antigen concentration needed variable efficiency Disadvantages
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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
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Safety Live vaccines Killed vaccines Single proteins Immunogenicity
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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
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Vaccination - like a minor infection at an epithelial surface
Antibody Tc-dependent M activation Cytotoxic T cells
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T cell-mediated immunity
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Function of Antibody -1
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Function of Antibody -2 Opsonisation IgG1, IgG3, IgG4, IgA
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Function of Antibody -3 Antibody-dependent cellular cytotoxicity(ADCC)
IgG1, IgG3
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Function of Antibody -4 -Activation of the complement cascade IgG IgM
IgA IgM
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The affinity as well as the amount of antibody increases with repeated immunization
© 2001 by Garland Science
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Primary vs Memory response
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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
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Adjuvants Alum. hydroxide suspension
Pertussis toxin - mixed with Diphtheria and Tetanus toxoid DTP triple vaccine
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Polysaccharide vaccines
Encapsulated bacteria Polysaccharide vaccines Against Hib, menigococcus, pneumococcus. Capsular PS, virulence factor
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Immune response to PS vaccines
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Limitations of polysaccharide vaccines
T cell independent antigen: Stimulate B cell for antibody production without T-cell help Poorly immunogenic in infancy (Not effective in young children) No memory But Effective in older children and adults
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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
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Conjugate polysaccharide vaccines
Protein Ag attached to PS allow T cells to help PS-specific B cells. © 2001 by Garland Science
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Conjugate polysaccharide vaccines
© 2001 by Garland Science
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Immune response to Conjugate PS vaccines
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Advantages of conjugate vaccines
More immunogenic than PS vaccines Effective in young children as well T cell involvement and Immunological memory Long-term protection
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Limitation of conjugate vaccines
Limited serotype coverage Increase in non-vaccine serotypes after vaccination expensive
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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.
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Passive Immunisation Provide antibodies - whole serum or immunoglobulin (mainly IgG). Provide immediate protection, eg rabies, tetanus, diphtheira. No long term protection.
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Haemolytic disease in the newborn
RhD- mother with RhD+ fetus can develop anti-Rh antibodies and cause haemolysis to the newborn and subsequent pregnancy. 46
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Antenatal and postnatal administration of anti-RhD immunoglobuin to RhD- mother can prevent haemolysis in the newborns
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SUMMARY
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