12 - vaccine adjuvants Flashcards
changes in preferred vaccine types over time
used to rely on live vaccines
now prefer sub-unit vaccines
why do we now prefer subunit vaccines
perceived way to reduce side effects
focused
safe
reliable
subunit used for plague vaccine
component of bacterium’s T3SS
why use adjuvants
increased intensity/magnitude of response increased duration of immune response no need for repeat vaccines can use lower doses allows modification of immune response
why do adjuvants increase intensity of immune response
they increase the antibody and T cell response
3 types of adjuvant
1 - depot effects
2 - delivery vehicles
3 - immune stimulators
overall method of depot effect adjuvants
antigen is sequestered at the site of infection and then released over time
benefit of depot effect adjuvants
antigen is released and exposed to immune system over a longer period of time
2 ways to carry out depot effect
1 - physically trap protein antigen into a capsule structure which breaks down over time
2 - formulate the antigen to be embedded in a matrix
most widely used adjuvant method
depot effect
protein antigen embedded in a matrix
examples of depot effect adjuvants
liposome
- antigen encapsulated in lipid bilayer
aluminium salts
- antigen absorbed onto gel-like matrix
overall method of delivery vehicle adjuvants
antigen is targeted to APC/immune cells for efficient delivery
2 systems used in delivery vehicle adjuvants
1- virus-like particles
- capsule loaded in vaccine antigen
2 - liposomes
- fuse vaccine antigen with host cell membrane to deliver its contents into the cytosol and elicit a T cell response
overall method of immune stimulator adjuvants
activates elements of the innate immune system to modify the immune response
e.g. production of specific cytokines to elicit optimal adaptive resposne
pathway stimulated by immune modifier adjuvants
TLR pathway
2 TLR signalling pathways
MyD88
TRIF
how do adjuvants modify the immune system
they act on APCs and CD8/CD4 t cells
effect of adjuvants on APCs
increase their efficiency at presenting (MHC I or II)
effect of aduvants on T cells
switch them on
examples of a toll agoinst
LPS
however too risky to actually be used
why are toll agonists risky
you have to balance their adjuvant effects against their toxic effect
e.g. over agonsing TLRs can lead to cytokine storm (sepsis)
aims of modification of LPS
reduce LPS toxicity
retain LPS adjuvant activity
method of modification of LPS
remove phosphate group from Lipid A to make MPLA
Lipid A
component of LPS that is recognised by TLRs
anchors molecules to bacterial cell wall
has important phosphate group
MPLA
monophosphoryl lipid A
Importance of MPLA as an adjuvant
non-toxic
makes TLR signalling terminate at inflammatory mediators
only activates TRIF pathway
therefore different repertoire of cytokines/inteferons produced
other molecules that could b used as adjvants
DNA molecules
peptodglycan
why dont live and killed vaccines require adjuvants
the entire molecule/cell is injected which is sufficient to enter the cytosol and activate the pathways
the entire cell has the ability to target the antigen by itself
which type of vaccine are adjuvants essential for
sub unit vaccines
example of adjuvants causing side ffects in vaccines
adjuvants cause narcolepsy side effects in influenza H1N1 vaccine
