Lecture 3 - Vaccines

Question 1

Examples of live attenuated virus vaccine
1)
2)
3)
4)

Answer 1

1) Sabin polio vaccine
2) MMR
3) Varicella
4) Yellow fever

Question 2

Examples of inactivated virus vaccine
1)
2)

Answer 2

1) Salk polio

2) Tick-borne encephalitis

Question 3

Examples of protein subunit vaccines
1)
2)
3)

Answer 3

1) Hepatits B
2) HPV
3) Seasonal flu

Question 4

HIV cell entry process
1)
2)
3)

Answer 4

1) gp120 binds to CD4. This exposes the coreceptor binding site on gp120 for CCR5
2) gp41 inserts fusion peptides (HR1, HR2) into the cell membrane
3) 6-helix bundle formation. Membrane fusion

Question 5

What are the most common targets for potential HIV vaccines?

Answer 5

gp120, gp41

Question 6

What is an escape variant?

Answer 6

A mutated epitope of a virus, whose original epitope was targeted by the immune system

Question 7

Failed HIV vaccines
1)
2)
3)

Answer 7

1) Vax04 (vaxgen)
2) STEP
3) RV144

Question 8

Outcome of STEP trail

Answer 8

Increase in disease

Question 9

Outcome of RV144 trial

Answer 9

~20% protection afforded

Question 10

Type of vaccine that was Vax04

Answer 10

Recombinant monomeric env protein in alum

Question 11

Type of vaccine that was STEP

Answer 11

Recombinant type-5 adenovirus vector with HIV-1 T cell antigens
NO ENV PROTEIN

Question 12

Type of vaccine that was RV144

Answer 12

Recombinant poxvirus vector + booster with env protein

Question 13

How does HIV evade the immune system?
1)
2)
3)
4)
5)

Answer 13

1) Contains regions with extreme tolerance for mutation
2) Very high mutation rate
3) Glycan shield of gp120.
4) Unstable association between gp120 and gp41 –> shedding of membrane trimers, exposure of irrelevant antigens
5) Highly conserved coreceptor binding site on gp120 is covered by glycans until binding with CD4 occurs

Question 14

Number of glycans normally attached to each gp120 trimer

Answer 14

20-30

Question 15

What is enriching for antibodies that recognise the CD4 binding site on gp120?
1)
2)
3)
4)

Answer 15

1) Produce a probe that mimics the CD4 binding site.
2) Produce another probe that is the CD4 binding site with a single amino acid change within the binding site.
3) Select for antibodies which bind the CD4 probe, and not the variant.
4) Using these probes, isolate B cells which produce antibodies against the Cd4 binding site.

Question 16

What is large-scale isolation of bNt Mabs form memory B cells?

Answer 16

1) Sort individual IgG B cells that bind to a modified gp160 trimer called 2CC
2) Recover IgV genes from each cell.
3) Reexpress as recombinant, complete IgG in test tube.

Question 17

How are different cell types identified?

Answer 17

Flow cytometry

Question 18

What does bNt Mabs stand for?

Answer 18

Broadly-neutralising monoclonal antibodies

Question 19

What is unusual about some bNt Mabs?

Answer 19

They don’t show evidence of coming from anti-HIV B cells

Germline antibody (without somatic hypermutation) doesn’t bind to HIV antigens.

Question 20

What are ‘waves’ of antibody immunity?

Answer 20

As the virus mutates, antibodies are made against different, more conserved epitopes.

The virus has an increasingly narrow range of epitopes to change

Antibody response becomes more potent, greater breadth

Question 21

How must broadly-neutralising antibodies be delivered to be effective at controlling HIV?

Answer 21

As a penta-therapy (five different kinds)

With fewer than five different types of bNt, response is too small.

Question 22

Limitations to therapy with broad neutralising antibodies

Answer 22

When treatment with antibodies stops, virus is resurgent