L4/5: Host defence and vaccine development

Question 1

What is the function of RIG-I?

Answer 1

• RIG-I like helicases recognise RNA in the cytoplasm (not endosomes)
• RIG-I and MDA5 from a complex that interacts with dsRNA and triggers a strong type I IFN response as well as inflammatory response

Question 2

What does TLR3 detect and induce as a consequence?

Answer 2

• dsRNA
• inflammatory response

-WNV exploits this to pass through BBB

Question 3

What do TLR7 and 9 detect and induce upon activation?

Answer 3

• ssRNA and unmethylated DNA respectively

- lots of these on plasmacytoid DCs which express type I IFN

Question 4

What are the 4 main IFN effector pathways?

Answer 4

• ISG15 ubiquitin-like pathway
• MxGTPase pathway
• 2’, 5’-oglioadenylate-synthase-direct ribonuclease L pathway (OAS-RNaseL)
• Protein kinase R pathway (PKR)

Question 5

What are the requirements of an effective vaccine?

Answer 5

• safe (will not cause disease)
• minimal side effects
• induces protective IR (innate and cellular)
• practical (cost, biologically stable, easy administration and public must see more benefit than risk)

Question 6

What are the key differences between live and inactivated vaccines?

Answer 6

Live = virus has been changed in some way eg reassortment or in recombinant viral vector(s)

Inactivated = virus-like particles or subunit vaccine (purified components but not all, eg. antigen or peptides)

Question 7

List 2 pros and cons of live attenuated vaccines.

Answer 7

Pros = No adjuvant needed, good CMI and Ab induction, provides immunity to all Ags, low viral dose needed, single dose

Cons = can revert back to wt, relatively poor stability

Question 8

List 2 pros and cons of inactivated vaccines.

Answer 8

Pros = impossible to revert to wt, good stability,

Cons = poor CMI, not immune to all Ags, high dose needed, adjuvant needed, boosters often needed

Question 9

List the factors favouring virus eradication. (6)

Answer 9

• limited to humans
• does persistent infection occur?
• 1 or many serotypes?
• Is the Ag stable?
• safe/effective vaccine
• is the disease serious?

Question 10

What are the three types of subunit vaccines?

Answer 10

• viral proteins purified from virions (eg. Hep B)
• Recombinant proteins
• Synthetic peptides

Question 11

What do antivirals usually target?

Answer 11

• Virus replication

- Means of cell entry/exit