12 - vaccine adjuvants

Question 1

changes in preferred vaccine types over time

Answer 1

used to rely on live vaccines

now prefer sub-unit vaccines

Question 2

why do we now prefer subunit vaccines

Answer 2

perceived way to reduce side effects
focused
safe
reliable

Question 3

subunit used for plague vaccine

Answer 3

component of bacterium’s T3SS

Question 4

why use adjuvants

Answer 4

increased intensity/magnitude of response
increased duration  of immune response
no need for repeat vaccines
can use lower doses
allows modification of immune response

Question 5

why do adjuvants increase intensity of immune response

Answer 5

they increase the antibody and T cell response

Question 6

3 types of adjuvant

Answer 6

1 - depot effects
2 - delivery vehicles
3 - immune stimulators

Question 7

overall method of depot effect adjuvants

Answer 7

antigen is sequestered at the site of infection and then released over time

Question 8

benefit of depot effect adjuvants

Answer 8

antigen is released and exposed to immune system over a longer period of time

Question 9

2 ways to carry out depot effect

Answer 9

1 - physically trap protein antigen into a capsule structure which breaks down over time

2 - formulate the antigen to be embedded in a matrix

Question 10

most widely used adjuvant method

Answer 10

depot effect

protein antigen embedded in a matrix

Question 11

examples of depot effect adjuvants

Answer 11

liposome
- antigen encapsulated in lipid bilayer

aluminium salts
- antigen absorbed onto gel-like matrix

Question 12

overall method of delivery vehicle adjuvants

Answer 12

antigen is targeted to APC/immune cells for efficient delivery

Question 13

2 systems used in delivery vehicle adjuvants

Answer 13

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

Question 14

overall method of immune stimulator adjuvants

Answer 14

activates elements of the innate immune system to modify the immune response
e.g. production of specific cytokines to elicit optimal adaptive resposne

Question 15

pathway stimulated by immune modifier adjuvants

Answer 15

TLR pathway

Question 16

2 TLR signalling pathways

Answer 16

MyD88

TRIF

Question 17

how do adjuvants modify the immune system

Answer 17

they act on APCs and CD8/CD4 t cells

Question 18

effect of adjuvants on APCs

Answer 18

increase their efficiency at presenting (MHC I or II)

Question 19

effect of aduvants on T cells

Answer 19

switch them on

Question 20

examples of a toll agoinst

Answer 20

LPS

however too risky to actually be used

Question 21

why are toll agonists risky

Answer 21

you have to balance their adjuvant effects against their toxic effect
e.g. over agonsing TLRs can lead to cytokine storm (sepsis)

Question 22

aims of modification of LPS

Answer 22

reduce LPS toxicity

retain LPS adjuvant activity

Question 23

method of modification of LPS

Answer 23

remove phosphate group from Lipid A to make MPLA

Question 24

Lipid A

Answer 24

component of LPS that is recognised by TLRs
anchors molecules to bacterial cell wall
has important phosphate group

Question 25

MPLA

Answer 25

monophosphoryl lipid A

Question 26

Importance of MPLA as an adjuvant

Answer 26

non-toxic
makes TLR signalling terminate at inflammatory mediators
only activates TRIF pathway
therefore different repertoire of cytokines/inteferons produced

Question 27

other molecules that could b used as adjvants

Answer 27

DNA molecules

peptodglycan

Question 28

why dont live and killed vaccines require adjuvants

Answer 28

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

Question 29

which type of vaccine are adjuvants essential for

Answer 29

sub unit vaccines

Question 30

example of adjuvants causing side ffects in vaccines

Answer 30

adjuvants cause narcolepsy side effects in influenza H1N1 vaccine