Viral vaccines Flashcards
What year was the last case of naturally acquired smallpox?
1977
What are the clinical presentations of smallpox?
Pustules that turn into scabs
What percentage of people would die in villages when smallpox was rampant?
40% of previously unexposed people would die. Mostly young.
What important observation did Edward Jenner make?
Milk maids in countrysides were immune to smallpox. Now we know because they gained immunity from being exposed to Cowpox
How did Edward Jenner invent vaccines?
Vacca = cow
Inoculated with cowpox postule taken from milk.
Then virolated the son of his friend a few months later with smallpox. The child became immune.
What control was used before the development of the smallpox vaccine?
The people would be inoculated with scabs from smallpox infected patients. The scabs would be dragged on skin or inhaled. This was very risky since 1% of the population died.
What is the goal of vaccines
To provide solid immunological memory in order to produce rapid secondary immune responses.
What are the signs of a good vaccine?
Formation of immunological memory
Creates threshold level of plasma antibodies to neutralise the virus
How do vaccines work?
Antigen from the vaccine is taken up by dendritic and antigen-presenting cells that present the antigen to B cells and T cells.
B cells activate and proliferate leading to the production of antibodies and B cell memory.
T cells differentiate into CD4 T cells and CD8 T cells.
The CD4 T cells produce cytokines that aid the B cell activation and proliferation and CD8 T cell antigen presentation. They also contribute to T cell memory.
CD8 T cells produce a CD8 T cell response and contribute to T cell memory.
Commonly used types of vaccines
Live attenuated
Inactivated
Sub-unit
What is a live attenuated vaccine?
A less virulent form of the agent that replicates.
Used in MMR - measles, mumps and rubella
What is an inactivated vaccine?
Chemically inactivated virus or lysates of cells infected with the virus.
Used in flu
What is a sub-unit vaccine?
An isolated recombinant component of an agent (as small as a single protein)
Used in HBV
Why was smallpox the ideal candidate for eradication?
- Worked when freeze-dried and easily transported
- Can see if someone is immune
- Everyone gets symptoms if infected. Not asymptomatic.
- No animal reservoir
- Once you have gained immunity it is lifelong
- Vaccine is easily delivered
What two concepts is surveillance containment based around?
R0 and herd immunity
What is R0?
The ability for an agent to spread and transmit.
Highest R0 is for measles, R0=12-18
If R0 = 1 then stable
If R0 > 1 then will spread
If R9 < then will die out
Goal for surveillance containment is to have R0 below 1
How does herd immunity work?
The virus needs living, non-immune host in order to transmit. If it is surrounded by a sea of immune people however, transmission becomes impossible. Therefore, non-immune people are protected from the virus as much as immune people.
What does ring immunity entail?
Track traces with rash
Quaranty infected people
Vaccinate people around them
How was smallpox eradicated?
At first, WHO wanted to vaccinate everyone. This was managed in America but soon realised it was a time-consuming, arduous process.
Instead used quarantine surveillance and herd immunity.
What are the advantages of inactivated and subunit vaccines?
Apt for immunocompromised patients
Safe since no infectious agent present
What are the disadvantages of inactivated and subunit vaccine?
Not lifelong Need multiple doses Safety - may not be inactivated properly by chemical process Adjuvants required CTL response is poor
What are the advantages of attenuated live vaccines?
More of a natural, realistic response
Life-long/ long-term immunity
Cheap
What are the disadvantages of attenuated live vaccines?
Safety is decreased since viable, replicating viruses are used that could form a mutant strain.
Not suitable for immunocompromised
Can spread from recipient
Unrecognised agents may be present that are undetected during manufacturing
How do we know the national immunisation programme works?
After a vaccine was introduced to combat rotavirus, a virus that caused disease in many infants, number of patients dropped dramatically.
Polio
Next candidate for eradication due to global vaccination schemes.
90% of population is vaccinated.
Two vaccines being used:
- Oral polio vaccine
- Inactivated polio vaccine
What is the future of viral vaccines?
Structural vaccines without the virus.
When Flu binds to the CSM of host cells via Haemagglutinin, some proteins on their receptors could be targeted by the immune system. These are however hidden by viral proteins and only shown during the conformational change.
Proteins expressing the epitopes of the protective proteins could be crystallised and injected to the host to amount an immune response to the protective epitopes.
