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VACCINES. 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. No vaccine is 100% effective! Most that are used in North America are between 70 and 95% effective - PowerPoint PPT Presentation
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VACCINES
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.
No vaccine is 100% effective! Most that are used in North America are between 70 and 95% effective
Vaccines provide both Individual benefit and a Public health benefit.
“herd immunity”
History
• Mummies• China/India Crusaders
• W Europe: fatality rate 25%• History changed:
Cortes Louis XIV
• 1% v. 25% mortality• Life-long immunity: No
drift or shift (proof reading)
• UK: 1700’s• China: 1950
• Pakistan/Afghanistan/Ethi
opia 1970
Variolation
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)
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
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.
TWO FORMS OF VACCINES
PROPHYLACTIC THERAPEUTIC
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.
ingredients
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 withaluminum
Vaccine Type Disease
Live, attenuated vaccine
Measles, mumps, rubella, polio (Sabin vaccine), yellow fever
Inactivated or “killed” vaccine
Cholera, flu, hepatitis A, Japanese encephalitis, plague, polio (Salk vaccine), rabies
Toxoid vaccine Diphtheria, tetanus
Subunit vaccines Hepatitis B, pertussis, pneumonia caused by Streptococcus pneumoniae
Conjugate vaccines
Haemophilus Influenza type B, pneumonia caused by Streptococcus pneumoniae
DNA vaccines In clinical testing
Recombinant vector vaccines
In clinical testing
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
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.
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 1) Mutation; reversion to virulence 2) Spread vaccine not standardized--may be
mutated 3) Problem in immunodeficiency disease
CONJUGATE VACCINE
Polysaccharide coat
Bacterium
toxoid
Currently, conjugate vaccines are available to protect against a type of bacterial meningitis caused by Haemophilus influenzae 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.
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
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
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)