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VACCINE IMMUNOLOGY
LECTURE 16, 17/11/2015
• Vaccination – named from the use of vaccinia, or cowpox, to induce immunity to variola (smallpox) in humans.
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.
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.
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 .
History of vaccination
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
1 July 1796Jenner used virulent smallpox matter to challenge James Phipps.Experiment successful: Phipps survived many subsequent exposure over 20 yrs
14 May 1796Edward Jenner used material from a cowpox pustule on the hand of Sarah Nelmes to vaccinate James Phipps (8 yr boy).
• 300 million people died of smallpox in the first three-quarter of the 20th Century.
• Smallpox eradicated in 1979 because of mass vaccination programme
Smallpox vaccination
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.
Infant vaccination programmes have saved approx. 3 million deaths worldwide annuallyHepatitis 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)
Vaccination saves lives
Major diseases that could be prevented by no effective vaccines
yet
1. ActiveAdministration of antigen (modified infectious agent or toxin) resulting in active production of immunity eg. antibodies
2. PassiveAdministration of antibody-containing serum or sensitised cells
Types of immunisation
Active• natural (unintended)• deliberate - vaccination
Passive
• Placental transfer (IgG)• colostral transfer (IgA)• transfer of human Ig or cells
• Safe - no significant side effects
• Effective, and preferably long-lasting
• Stable in storage
• Cost-effective for the target population
A good vaccine should be:
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
• Polysaccharide (PS), conjugate PS
eg. Pneumococcal PS, meningococcal PS
• Recombinant DNA products / purified proteins
eg. hepatitis B, influenza proteins
Subunit
Types of vaccines
Live vaccines
• single, small dose• given by natural route• local & systemic immunity• resembles natural infection
Advantages
• contaminating virus, • reversion to virulence• inactivation by climatic changes
Disadvantages
Inactivated (killed) vaccines
• safe• stable, so for each batch the safety and efficiency is known
Advantages
• multiple doses and boosters needed• given by injection - unnatural route• high antigen concentration needed• variable efficiency
Disadvantages
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
Killedvaccines
Singleproteins
Immunogenicity
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
AntibodyTc-dependent M activationCytotoxic T cells
T cell-mediated immunity
Function of Antibody -1
Opsonisation
IgG1, IgG3, IgG4, IgA
Function of Antibody -2
Function of Antibody -3
Antibody-dependent cellular cytotoxicity(ADCC)
IgG1, IgG3
Function of Antibody -4-Activation of the complement cascade
IgGIgA
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=
enhancedresponse
• 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
Against Hib, menigococcus, pneumococcus.
Capsular PS, virulence factor
Encapsulated bacteria
Immune response to PS 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
Limitations of polysaccharide vaccines
Making PS Ag T-cell dependent- conjugate vaccines
PS conjugated to a carrier protein to create a “T cell antigen”
polysaccharide
Tetanus toxoid
• 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
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 orimmunoglobulin (mainly IgG).
• Provide immediate protection, eg rabies, tetanus, diphtheira.
• No long term protection.
47
Haemolytic disease in the newborn
RhD- mother with RhD+ fetus can develop anti-Rh antibodies and cause haemolysis to the newborn and subsequent pregnancy.
Antenatal and postnatal administration of anti-RhD
immunoglobuin to RhD- mother can prevent haemolysis in the newborns
SUMMARY
Innate
A r ti f ic ia l N a tu ra l
P ass ive
A r ti f ic ia l N a tu ra l
A ctive
Acuired
Im m unity
The end