Lecture 12 - Vaccine Adjuvants Flashcards
Explain why vaccine adjuvants are required for some vaccine but not others Explain how the different types of adjuvants work Have an understanding of the research on vaccine adjuvants that is required
Why are vaccine adjuvants needed?
Increase magnitude of immune response
Increase duration of protective immunity
Allows the type of immune response to be modified
May allow lower doses of the vaccine to be used
What are the types of desired effect an adjuvant may have?
Depot effects
Act as delivery vehicles
Act as immune stimulators (modifiers)
What are the depot effects of a vaccine adjuvant?
The antigen is sequestered at the site of injection, and become released over time, which increases the duration of exposure of the antigen to the immune system
This effect ensures that the protein delivered by injection doesn’t become sequestered at the site of injection so it doesn’t leach away, reducing the requirement for repeat injections
What are the 2 mechanisms used to achieve depot effects in vaccine adjuvants?
Physical entrapment - protein packaged in shell that breaks down slowly releasing protein or polysaccharide
Antigen is formulated so it becomes embedded in a matrix - This allows antigen to become physically adsorbed and slowly desorbed over time.
Give 2 examples of depot effect adjuvants
Aluminium salts - form a gel like matrix and are the most widely used adjuvant
Liposomes - encapsulate the antigen with a double lipid bilayer which gradually breaks down
How do adjuvants act as delivery vehicles?
The antigen is targeted to immune cells e.g. APCs in order to elicit a specific pathway of immune response.
What are the 2 mechanisms used to achieve delivery system effects in vaccine adjuvants?
Virus like particles - Use a viral capsid without any nucleic acids inside, but instead loaded with vaccine antigen. This works like a trojan horse to get the vaccine to be taken up by the APC.
Liposomes - These can also be used as particle delivery systems along with depot effect adjuvants. The synthetic cell membrane can fuse with the host cell membrane and deliver its contents directly into the cytosol. This enables the vaccine to elicit a CD8 response (processed by MHCI)
How do adjuvants act as immune stimulators (modifiers)?
The adjuvant activates elements of the (innate) immune system to modify the response. It does this via the promotion of production of chemokines and cytokines. This generally gives the immune system a more potent response to the antigen of interest
What is the 4 letter acronym for the molecules that the innate immune system recognises?
PAMPS
Which branch of the immune system do adjuvants that act as immune stimulators target?
Innate immune system, provoking the production of cytokines and chemokines allowing a more productive adaptive response. This is done via the use of PAMPs
Which signalling pathway do immune stimulatory adjuvants target?
TLR signalling pathway
How does LPS elicit an immune response?
TLR4 can’t bind directly to LPS so must first form a complex with MD2
MD2 complex binds TLR4
Downstream pathways are switched on via myd88 and trif molecules
This causes production of cytokines and chemokine which are required for maturation of the immune response
How do cytokines, chemokine and interferons shape the immune response?
They act as ‘toll agonists’ and elicit the following effects:
Act on APCs making them more efficient at presenting antigens via MHCI or II pathways
Some cytokines also switch on CD4 or CD8 t cell activity independently
What molecule can be produced from LPS, with a lower toxicity and the potential to be used as an adjuvant?
Monophosphoryl lipid a (MPLA). It does however only activate signalling via the TRIF pathway and not MyD88.
Which type of vaccines don’t require adjuvants? Why?
Live and killed vaccines.
This is because they are self adjuvanting as they are whole microorganisms and already contain things like TLR agonists to direct the immune response
