1. VACCINES

3. DEFINITION A vaccine is biological preparation that improves immunity to a particular disease, a vaccine typically contains a disease causing micro-organisms often weakened or killed.

4. No vaccine is 100% effective! Most that are used in North America are between 70 and 95% effective • Vaccines provide both Individualbenefit and a Public health benefit. • “herd immunity”

5. History • Mummies • China/India Crusaders • W Europe: fatality rate 25% • History changed: • Cortes • Louis XIV

6. Variolation • 1% v. 25% mortality • Life-long immunity: No drift or shift (proof reading) • UK: 1700’s • China: 1950 • Pakistan/Afghanistan/Ethiopia 1970

7. Small pox • Vaccination • Jenner 1796 : Cowpox/Swinepox • 1800’s Compulsory childhood vaccination • 1930’s Last natural UK case • 1940’s last natural US case • 1958 WHO program • October 1977: Last case (Somalia)

8. Reasons for success of smallpox vaccination • No animal reservoir • Lifelong immunity • Rare Subclinical cases • Infectivity does not precede overt symptoms • One Variola serotype • Effective vaccine • Major commitment by governments

9. Estimated Herd Immunity thresholds for vaccine preventable diseases • Disease Transmission R0[N] Herd immunity threshold • Diphtheria Saliva 6-7 85% • Measles Airborne 12-18 83 - 94% • Mumps Airborne droplet 4-7 75 - 86% • Pertussis Airborne droplet 12-17 92 - 94% • Polio Fecal-oral route 5-7 80 - 86% • Rubella Airborne droplet 5-7 80 - 85% • Smallpox Social contact 6-7 83 - 85% ^  - R0 is the basic reproduction number, or the average number of secondary infectious cases that are produced by a single index case in completely susceptible population.

10. TWO FORMS OF VACCINES PROPHYLACTIC • Prevent future infection by any means. e.g. to prevent or ameliorate the effects of a future infection by any natural or "wild" pathogen). • Prevent severity of infection problems already occurred. e.g. vaccines against cancer are also being investigated. THERAPEUTIC

11. ingredients

12. Preparation of vaccine Separate two effects of organism Formalin can be used Use antigen part of virus Attenuate virus aging altering or mutating Toxins of toxoid vaccines are treated with aluminum

15. Inactivated or killed vaccine • Advantages of inactivated vaccine • Gives sufficient humoral immunity if boosters given • No mutation or reversion • Can be used with immuno- deficient patients • Disadvantages of inactivated vaccines • Boosters needed • Many of them donot raise immunity • Higher cost

16. Attenuation • ATTENUATION is usually achieved by passage of the virus in foreign host such as embryonated eggs or tissue culture cells. • These tend to be less virulent for the original host. In Sabin polio vaccine, attenuation was only achieved with use of high inocula and rapid passage in primary monkey kidney cells. • The viruses became overgrown with a less virulent strain (for humans) that could grow well in non- nervous tissue but not in CNS. Non-virulent strains of all three polio types produced for the vaccine.

17. Live attenuated vaccine • Advantages of Attenuated Vaccine • 1)Activates all phases of immune system. Can get humoral IgG and local IgA 2)Raises immune response to all protective antigens . Inactivation may alter antigenicity. 3)More durable immunity; more cross-reactive • Disadvantages of Attenuated vaccine • Mutation; reversion to virulence • Spread vaccine not standardized--may be mutated • Problem in immunodeficiency disease

18. Conjugate vaccine Currently, conjugate vaccines are available to protect against a type of bacterial meningitis caused by Haemophilusinfluenzae type b (Hib). Meningitis, an inflammation of the fluid-filled membranes that protect the brain and spinal cord, can be fatal, or it can cause severe, life-long disabilities such as deafness and mental retardation. Bacterium toxoid Polysaccharide coat

19. DNA VACCINES • The deliberate introduction of a DNA plasmid carrying a protein-coding gene that transfects • Cells in vivo at very low efficiency and expresses an antigen that causes an immune response. • These are often called DNA vaccines but would better be called DNA-mediated or DNA-based

20. Advantages of DNA vaccines • 1) Plasmids are easily manufactured in large amounts • 2) DNA is very stable • 3) DNA resists temperature extremes so storage and transport are straight forward • 4) DNA sequence can be changed easily in the laboratory. This means that we can respond to changes in the infectious agent

21. Possible Problems • 1) Potential integration of plasmid into host genome leading to insertional mutagenesis • 2) Induction of autoimmune responses (e.g. pathogenic anti-DNA antibodies) • 3) Induction of immunologic tolerance (e.g. where the expression of the antigen in the host may lead tospecific non-responsiveness to that antigen)