Scientific Basis of Vaccines Flashcards
What is a vaccination?
A vaccine contains material from an organism that will actively enhance adaptive immunity.
It produces an immunologically “primed” state that allows for a rapid secondary immune response on exposure to antigen, causing prevention of DISEASE, but not infection.
It is long-lasting, and that requires immunological memory.
What is the rational for vaccines?
There are two rationales for vaccines.
The first is to protect the individual from diseases that can lead to dire consequences. If not, at the very least we want to decrease the rate and/or severity of the disease.
The second is to protect the population, so it is a public health intervention. The aim is herd immunity. If the virus is still around, we can make vulnerable members of the community susceptible to the disease. This helps prevent outbreaks and epidemics.
Vaccines can lead to the eradication of diseases.
What are some concepts that can be extrapolated from Edward Jenner’s vaccine discover?
- the challenge dose on the young boy proves you could get protection from infection
- it introduces the concept of attenuation
- it also introduces the concept that prior exposure to the agent boosts protective response
- it proves that cross-species protection was possible - due to the antigenic similarity
How did we achieve the eradication of smallpox?
- through vaccination programmes (vaccinate a ring of people around the infected person)
- case finding (surveillance)
- movement control
Why was the eradication of smallpox possible?
- there were no sub-clinical infections (no such thing as asymptomatic infection)
- after recovery, the virus was eliminated - there were no carrier states
- there was no animal reservoir (no way it can come back from the environment after being cleared)
- it had an effective vaccine (cross-species, attenuated, live vaccinia virus = very effective)
- it also had a slow spread, and poor transmission
Explain the vaccination paradox.
If you vaccinate more people, and there is less infectious pool in the community, you end up not having something called natural boosting. Natural boosting is the boosting of your immune system via exposure to infections in the community. You may not see the disease again, but at least your immune system is familiar with it and has the antigens ready for it.
Thus, we need to ensure that the vaccine uptake rates stay high, because as soon as they drop, we would see an increase in the disease.
What are the different types of immunity that vaccines can enhance and how?
ACTIVE IMMUNITY:
We can enhance this using natural exposure (carriage), infection and vaccinations (all of which give us long-term effects).
PASSIVE IMMUNITY:
Here, we can use antibodies from another serum source for prophylaxis and/or treatment (for a short-term effect).
What are we trying to get out of vaccines?
They need to induce the correct TYPE of response (by secreting the correct antibodies).
They also need to induce the response in the RIGHT PLACE.
What do we need to consider when making vaccines?
DURATION of protection we want. They could be in the form of boosters, short-term (for travel) or long-term (for immunity).
age of vaccination. For example, neonates have high levels of maternal antibodies after they are born that last for about 6 months; if we give a vaccine, it will have an immune response to it. This immunity wears off at about 9 months, so it is then that we start giving vaccines for the child to make their own antibodies.
the nature of the antigens themselves: if they are highly variable or monotypic (such as measles). If they are highly variable (or polytypic), we will be able to contact them quickly, despite already having been immunised against them before, as the antigen is constantly changing.
How do we overcome the poor recognition of polysaccharides in children under the age of two?
We need to conjugate the bacterial capsular polysaccharide with toxoids and outer membrane proteins.
This conjugated vaccine gives us long-lasting immunity and response in children.
Examples include the MenC vaccine for Neisseria meningitidis Group C, and the Hib vaccine for Haemophilus infleunzae Type B.
What are the three types of vaccines?
1) Live, attenuated organism.
2) Killed, whole organism.
3) Sub-unit vaccines.
Describe killed, whole organism vaccines.
It is used for pertussis, flu (old type), polio (Salk type), cholera, and HepA.
It can help boost immunity by driving it against the organism’s surface components.
After the first dose, you get some immune response, but it is not sustainable. So, you’ll get a booster injection to raise the levels again. A second boost is needed to ensure that the levels stay high enough to warrant a long-term secondary immune response.
Describe sub-unit vaccines.
It uses individual components of the pathogen, such as:
- proteins
- toxoids (diptheria, tetanus)
- peptides (synthetic)
- polysaccharide (though they are a poor antigen as they don’t drive a good immune response in children under the age of two)
We can use different types of proteins, such as:
- recombinant proteins
- sub-cellular proteins
- surface antigens (e.g. HepB, influenza haemogglutinins, menB)
- virulence determinant (e.g. aP-pertussis: adhesin + toxoid + outer membrane protein)
What are toxoids?
Toxins normally induce tissue damage and cause disease in some pathogen.
However, if we inactivate it using formaldehyde, we produce what is called a toxoid, which is antigenic and non-toxic. It can be used in vaccines to develop an immune response against a pathogen, and generate antibodies specific to the toxin, which gives us protection against the pathogen.
How exactly does the conjugation in the vaccine occur?
Conjugation links polysaccharide antigen to protein carrier (e.g. diphtheria or tetanus) that the infant’s immune system already recognises in order to provoke an immune response.
A polysaccharide by itself will not be well-recognized by infant B cells, and thus will not be able to generate that many antibodies.
However, if we link it to a protein, the B cell will be able to recognize the protein, and will present the protein to the T cell that will recruit cytokines that will encourage the B cell to recognize the polysaccharide. It will then be able to make antibodies of it, generating an immune response to second exposure.
