Vaccine 2

Question 1

subunit vaccines are

Answer 1

isolated components of microorganisms e.g. individual proteins or polysaccharides

Question 2

Subunit vaccine primarily provoke which response

Answer 2

antibody response

Question 3

antibody response (6)

Answer 3

1) agglutination
2) opsonisation
3) neutralisation
4) activation of complement
5) inflammation
6) antibody-dependent cell-mediated cytotoxicity

Question 4

protein processing pathways

Answer 4

CD5 T response- MHC2

CD8 T response-MHC I

Question 5

CD4 T cell response

Answer 5

proteins processed via endosomal pathway, which causes inflammation, macrophage activation and antibody production

Question 6

CD8 T cell response

Answer 6

proteins processes via cytosolic pathways

• kills infected cell
• cytotoxic T cell

Question 7

polysaccharide sub-unit vaccines are based on the fact

Answer 7

that all bacteria are coated in sugar

- different bacteria have very specific sugars- which makes them good vaccines

Question 8

the different combinations of polysaccharides make up

Answer 8

unique cell surface structures

- antibodies can be are again

Question 9

the different combinations give arise to

Answer 9

immunologically distinct polysaccharides

Question 10

Streptococcal pneumoniae is the

Answer 10

Major cause worldwide of community acquired pneumonia, bacterial meningitis, bacteraemia and otitis media
- causes systemic infections which are hard to treat due to the time of diagnosis being to late

Question 11

Streptococcal pneumoniae is a bacteria

Answer 11

that had an abundance of polysaccharide on its outer layer

Question 12

how are antibodies protective against streptococcal pneumoniae

Answer 12

opsonising- mostly

complement fixing

Question 13

issues with developing streptococcal polysaccharide vaccines

Answer 13

different strains have different polysaccharides on their surgave

Question 14

how many serotypes of pstreptococcal polysaccharide

Answer 14

90

Question 15

how do you develop a vaccine which has a potential of 90 different strains

Answer 15

o focus on the most abundant serotypes (the ones most likely to cause disease)
o especially meningitis and bacteraemia

Question 16

currently how many serotypes in vaccines against streptococcal pneumoniae

Answer 16

23

Question 17

Although the very group we want to protect against are the you and elderly do not respond well to polysaccharide vaccine

Answer 17

no memory, weak immune system

- adaptive immune system is weak

Question 18

why do polysaccharides provide weak immunity in the young and elderly?

Answer 18

polysaccharides are not processed i the same way as proteins e.g. - through the CD4/CD8 pathways- so don’t get protective responses such as cytokines, which cause inflammation, antibody production, macrophage activation

• cannot stimulate CD4/CD8
• immature antibody response

Question 19

immature antibody response with Streptococcal pneumonia vaccines

Answer 19

very few IgG- dominated by IgM- directly interact with b cells
- clonal proliferation of B cells

Question 20

how can we get around the issues surrounding streptococcal polysaccharide infections

Answer 20

• link the polysaccharide to a protein carrier
• means that it behaves more similarly to proteins
• turning o T cell activation
• MHC class 2 see the peptide and polysaccharide fragment
• more IgG

Question 21

example of a protein that can be tagged to the strecptoccal vaccine

Answer 21

diphtheria CRM197 toxin ( which is genetically modified- activate site region mutated to abolish toxicity)

Question 22

conjugate vaccines

Answer 22

are predominately used against streptococcal disease mix between polysaccharides linked to a protein carrier)

Question 23

streptococcal disease is a massive killer

Answer 23

in developing countries

Question 24

23-valent vaccine

Answer 24

¥ Pick the serotypes most likely to cause disease.
¥ Isolate polysaccharides from these serotypes (1, 2, 3, 4, 5, 6b, 7F, 8,9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F and 33F)

Question 25

what type of antigen are polysaccharides

Answer 25

T cell independent antigens

Question 26

Polysaccharides are t cel idnepdnent antigens

Answer 26

no involvement of antigens presenting cell, CD4+/8+ T cells. | - polysaccharides interact directly with B-cells

Question 27

Polysaccharides interact directly with

Answer 27

B cells - clonal proliferation of B cell - production of IgM antibody - poor antibody response in children and elderly - no memory

Question 28

conjugate vaccine

Answer 28

chemically couple protein- polysaccharide vaccine

Question 29

example of polysaccharide vaccines

Answer 29

``` ¥ Streptococcus pneumoniae - pneumonia ¥ Haemophilus influenzae - pneumonia ¥ Neisseria meningitidis - meningitis ¥ Salmonella typhi – typhoid fever ¥ Burkholderia pseudomallei - melioidosis ```

Question 30

mechanisms of T-cell activation by glyconjugate vaccine

Answer 30

1) glycoconjugate vaccine is internalised into an endosome of theB cell and processed into glycansaccharides and glycanpeptides 2) MHC II presentation of glycol peptide by MHC II to the ab receptor of CD4+ T cells 4) activation of the T cell by the carbohydrate/MHCII results in T-cell production o cytokines which mature the b cell to become a memory B cell

Question 31

vaccines which induce CD8+ T cell responses

Answer 31

- subunit vaccines evoke CD4= endosome | - we need a vaccine which gets into the cytosol

Question 32

which diseases required CD8+T cell response to clear infections

Answer 32

``` TB Salmonellosis Meliondosis Viral infection- yellow fever, influenza, measles Cancer vaccines ```

Question 33

CD8 T cell response is required anytime

Answer 33

where killing of host cell is required

Question 34

pathogens which growth within infected cell

Answer 34

require a response where the whole cell is destroyed

Question 35

it is difficult to develop vaccines

Answer 35

which induce CD8+ T cell responses

Question 36

CD8 T cells

Answer 36

kill via cytotoxicity

Question 37

approaches which induce a CD8 T cell response from vaccines

Answer 37

1) use live attenuated microbes | 2) using naked DNA vaccines

Question 38

Using live attenuated microbes to induce a CD8 T cell response

Answer 38

capable of replicating inside the cytosol- presenting protein antigens to the immune system via CD8 T cell responses - can survive long enough to establish an immune response - balance between over and under attenuation

Question 39

issues with live vaccines

Answer 39

may not be able to control infection by attenuated strain

Question 40

Using naked DNA vaccines to evoke a CD8 T cell response

Answer 40

- identify and produce gene coding for vaccine compoenent- protein - DNA is taken up into cytoplasm (muscle cells( and transcribed and translated - generate specific antigenic proteins - an immune response develops - cytosol response stimulates CD8 T cell responses

Question 41

issues with DNA vaccines

Answer 41

- difficult to control duration of exposure- how long the DNA will survive - works well in animals but not humans

Question 42

in theory DNA vaccines

Answer 42

combine the advantage of live and sub-unit vaccines e.g. West Nile Fever vaccine licensed for use in hordes – vaccines encode coat proteins e.g. Infectious hematopoietic necrosis vaccine licensed for use in fish- vaccine encode surface glycoprotein

Question 43

summary

Answer 43

- polysaccharides are often included in vaccines - to improve the response to the vaccine they are linked to a protein - developing vaccines which induce CD8 T cell responses is difficult