Vaccines and Vaccinology Flashcards
Edward Jenner invented vaccination in
1796 (smallpox)
Vaccines in use today
Human
Animal - livestock, pets, fish, wild animals (foxes immunised against rabies)
Wild animals can be immunised against
Rabies
Effective human vaccines
Diptheria
Polio
Measles
SSPE
Subacute sclerosing panencephalitis
Progressive caused by the measles virus
How many lives have vaccines saved in the last 20 year?
20 million
Smallpox once killed
5 million/year
Now eradicated
2 million more lives per year could be saved if
Vaccine programmes were extended to all countries
Polio will be the next infectious disease to be
Eradicated
Infection with some infectious diseases does not
Prevent re infection
Examples of diseases with naturally acquired immunity
Polio, smallpox, influenza, plague, anthrax, pertussis
Diseases that you can become immune to are good
Vaccine candidates
Diseases with no natural immunity are poor
Vaccine candidates
Examples of diseases with no naturally acquired immunity
HIV, malaria, TB, gonhorrea, schistosomiasis
Vaccines mimic
Exposure to the disease
Immunity to flu is
Strain dependent
Protective responses include
Antibodies
Cellular immunity
Antibodies
Proteins that circulate in the blood
Able to bind toxins, bacteria and viruses
Neutralise or promote clearance
Produced by B Lymphocytes
Cellular immunity
CD4 T cells - manage and manipulate immune response through cytokines
CD8 T cells - specialised cells that kill infected cells
A combination of Antibodies and T cells protects against disease
In differing ratios
Therefore different vaccines are needed
Types of vaccines
- Live vaccines
- Killed vaccines
- Subunit vaccines
- Naked DNA vaccines
Live vaccines
Microbes that have been modified (weakened) so they can infect but not cause disease
Good at inducing immune response
BCG, polio, yellow fever, typhoid, smallpox
Killed vaccinies
Killed with heat/formaldehyde
Does not induce very strong responses
Can be reactogenic
Subunit vaccines
Protein/polysaccharide fragments
Good for antibodies, not good for T cells
Pure components = few side effects
Diptheria, tetanus, anthrax, plague
Naked DNA vaccines
DNA fragment that codes for a protein is injected
DNA fragment produced in situ
Body recognises as foreign
Why are live vaccines less popular?
Live polio vaccine:
Reversion can occur
Switch from attenuated to a live disease causing microbe
Live polio vaccine
Live polio vaccine generated in the lab by culturing cells
Reason for attenuation not known at the time of creation of the vaccine
Once RNA analysis occurred, showed vaccine strain contains 57 mutations
Most critical mutation: Primary attenuating mutation is located in the virus’s internal ribosome entry site
Reversion of live polio vaccine
Outbreak of polio in 1999 in Hispanolia
Strains isolated from faeces of immunised infants
Showed partial or complete reversion to virulence
‘Shedding’
Live vaccines can
Shed
Dangerous for immuno compromised
Subunit vaccines are good at
Inducing antibody response
Subunit vaccines are not so good at
CD4 T cell (fair)
CD 8 T cell (poor)
A subunit vaccine against plague
Current vaccine ‘cutter’ is a killed whole cell vaccine
Very reactogenic, several doses needed
Subunit version needs:
F1 antigen - forms the capsule
V antigen - component of tip of Type III secretion system
F1 and V antigen in plague are
Protective subunits
F1 and V antigen are grown in E coli using
Genetic engineering
Sub unit vaccines can be produced in
Plants
F1 and V antigen have been grown in
Tomatoes
eating develops resistance to plague
Naked DNA vaccines generate
A broad range of immune responses
Good at antibodies, CD4 and CD8
Naked DNA vaccines do not work well
In humans (but do in most other mammals)
Naked DNA vaccines are difficult to
Regulate
ie. how do you switch it off?
West Nile Fever vaccine for horses is an example of
Naked DNA vaccine
Vaccine encodes coat protein
To be effective against viruses, vaccines need to activate
CD 8 T cells
as phage replicate inside host cells
Vaccines for the future
- Infectious disease (public health, bioterrorism, animals)
- Cancer (against tumor cell markers, or microbe-associated cancer, eg. HPV)
- Degenerative diseases
- To control addictive behaviour
