Regarding subunit vaccines, first of all looking at some
diseases that are caused by viruses that we can protect using
subunit vaccines - the Hepatitis B virus, there is a vaccine
based upon recombinant Hepatitis B surface antigen.
This is produced in Saccharomyces.
The human papillomavirus - there’s
a vaccine based upon recombinant
L1 major capsid proteins that self
assemble into virus-like particles.
Regarding protection against bacterial diseases using
subunit vaccines, there’s the DTaP, which is the acellular
pertussis vaccine which is inactivated pertussis toxin
and it has one or more other bacterial components.
For example, filamentous hemagglutinin
or pertactin which is an outer
membrane protein and fimbriae, plus
bacterial toxoid and tetanus toxoid.
And then we have the meningococcal serogroup B vaccines, based
upon recombinant Neisseria meningitides group B proteins.
Here we have an example of a polyvalent virus like
particle based vaccine, the Gardasil-9 vaccine.
This is a human papillomavirus
What that means-- it has nine
different antigens in it.
It uses virus-like particles derived from the major capsid,
the L1 proteins of nine different human papillomavirus types.
These are types 6, 11, 16,
18, 31, 33, 45, 52 and 58.
And these self-assemble into these recombinant virus-like
particles that are produced in Saccharomyces cerevisiae.
They are released from the yeast cells by cell disruption
and purified using chemical and physical methods.
They are then adsorbed onto preformed aluminium-containing
adjuvant called amorphous aluminium hydroxyphosphate sulfate.
They are given to females in the
age range 9 to 26 years old for the
prevention of cervical, vulvar, vaginal
and anal cancer and genital warts.
And to boys and young men aged 9 to 26 years old for
the prevention of anal cancer and genital warts.
So looking at toxoid vaccines, these are
chemically inactivated bacterial exotoxins.
They protect from disease
but not from infection.
Examples include tetanus
toxoid and diphtheria toxoid.
Here we can see bacteria
releasing a bacterial toxin.
This is pathogenic,
it can harm our cells.
It can be recognized by the antigen receptor on
B-lymphocytes and stimulate a memory B-cell response.
However by chemically inactivating
the toxin in the laboratory, one
can produce a harmless version of
it that has lost the pathogenicity.
And we refer to this form of the
inactivated toxin as a toxoid.
Although it has lost the ability to cause pathology,
it maintains enough of its structure so that it can still be
recognized by the B-cell receptor on the surface of
B-lymphocytes, and therefore still generate memory cells.
Purified bacterial capsular polysaccharides only elicit
IgM antibodies due to a lack of helper T-cell epitopes.
This can be overcome by
employing conjugate vaccines.
Conjugate vaccines comprise
polysaccharides coupled to a protein.
Tetatus or diphtheria toxoid
is often the protein of choice.
Using this strategy, it converts a T-independent
response to a T-dependant response.
So here we can see recognition of the polysaccharide by
the B-cell receptor on the surface of a B-lymphocyte.
But on its own, this would not recruit
helper T-cells and there would
be no class switching from IgM to
higher affinity IgG antibodies.
However by conjugating the polysaccharide
onto a protein, the complex
of the polysaccharide plus protein
will be taken up by the B-cell.
The protein component will be processed
into peptides and those peptides
will be shown to the T-cell receptor
on the surface of helper T-cells.
Following interaction of the B-cell with the T-cell,
the T-cell will release cytokines and the molecules
CD40 on the B-cell will interact with the CD40L
molecules on the surface of the helper T-cell.
And together, those interactions will cause class
switching from IgM to higher affinity IgG antibody.
So this class switching produces high
affinity IgG and also IgA antibody.
Examples of conjugate vaccines include
the Hib vaccine, Haemophilus influenza
type b capsular polysaccharide
that’s conjugated to tetanus toxoid.
The meningococcal conjugate vaccine where
serogroups A, C, W and Y capsular polysaccharides
are conjugated to CRM197, which is a
non-toxic variant of diphtheria toxin.
And the pneumococcal conjugate vaccine,
PCV13, where capsular polysaccharide
antigens of 13 different Streptococci
pneumonia serotypes are conjugated to CRM197.