Let’s look now at some of the individual
components that need to be present in a vaccine.
Well of course the most
obvious one is the antigen.
You want to generate a antigen
specific memory response.
You can use the whole organism.
Obviously you can’t use it unmodified
because it would cause the pathology that
the natural infection would cause, and
that’s not going to be very helpful is it?
But you can grow organisms so that
they lose some of their pathogenicity.
We call that a live
Or you can kill the organism.
Or you can take little bits of the organism, individual
antigens from the organism and use those as subunit vaccines.
You often need to add a carrier, particularly with subunit
vaccines because there may not be sufficient sequence to provide
helper T-cell epitopes; in other words, peptides that can be
shown by the MHC to the T-cell receptor on helper T-cells.
So particularly with subunit vaccines, they may be
coupled to a larger protein molecule as you can see here.
Often one also needs to add
something called an adjuvant.
Now an adjuvant is a substance that non-specifically
stimulates a specific immune response.
And they work in a number of ways but
predominantly they act as a depot so that the
antigen gets released over a period of time
rather than all being seen immediately.
And they also activate dendritic cells,
so it acts as a dendritic cell activator.
And they’re equivalent really to a PAMP,
to a Pathogen Associated Molecular Pattern;
causing dendritic cells to up-regulate the
co-stimulatory molecule CD80 and CD86.
And therefore providing a really
strong co-stimulation to T-cells.
Examples of adjuvants include a number of
aluminum salts - aluminium hydroxide, aluminium
phosphate, alum which is potassium aluminium
sulfate, or mixed aluminium salts.
AS03 is a oil-in-water emulsion containing
D-,L-alpha-tocopherol and squalene.
AS04 is aluminium hydroxide and monophosphoryl lipid A
which is a low toxicity derivative of lipopolysaccharide.
And LPS stimulates
toll-like receptor 4.
So it stimulates this Pattern Recognition
Receptor and causes activation of dendritic cells.
MF59 is a oil-in-water
emulsion of squalene.
And virosomes are double membrane lecithin-phospholipid
liposomes into which viral proteins can be incorporated.
So this is just a few examples of
adjuvants that have been developed.
By far the most commonly used at this time in vaccines
for administration to humans are the aluminium salts.
In what situations might
one want to use a vaccine?
Well, clearly protection from
infection and prevention of infection.
And most vaccines that are given now
are aimed at preventing infection.
So an example would be
the Oral Polio Vaccine.
However, there is the potential to control
existing infections by vaccination.
And Zoster would be
an example of that.
To prevent disease development
post-exposure; as long as the rabies
vaccine is given very shortly after
exposure, it can prove effective.
To prevent fetal infection - Rubella
is an excellent example here.
And to prevent or control cancer and the Human Papilloma virus
and the Hepatitis B virus vaccines are examples of this use.