vaccination

Question 1

• What is a vaccine?

- What is the aim of immunisation?

Answer 1

Something that stimulates the immune system, without causing serious harm or side effects

To provoke immunological memory to protect individual against a particular pathogen if they later encounter it

Question 2

• What 3 main areas do vaccines work in?

Answer 2

Prevention of entry - macrophages engulfing pathogen (opsonisation)

Boosting immune response - antigens in vaccine activating CD4 T cells 

Killing infected cells - CD4 triggering CD8 T cells and also activation of B cells to make Ig

Question 3

• What is in a vaccination?

Answer 3

Antigen in one of these forms:

- Inactivated protein
- Recombinant protein e.g. Hep B
- Live Attenuated Pathogen e.g. Polio/BCG
- Dead pathogen e.g. split flu vaccine
- Carbohydrate e.g. S.pneumoniae

Adjuvant

Stabilising stuff (e.g. Buffers)

Water

Question 4

• Give an example of an inactivated toxoid vaccine

- Describe what is meant by an inactivated toxoid vaccine

Answer 4

Tetanus toxoid vaccination

Chemically inactivated form of toxin

Question 5

• how does an active toxin work?

- Explain the mechanism of inactivated toxoid vaccines

Answer 5

Toxin binds to cell-surface receptor

Endocytosis of toxin-receptor complex

Dissociation of toxin releases active chain, which poisons cell

Neutralising antibody blocks further binding of toxin to cell surface receptor

Essentially, antibody blocks toxin from binding

Question 6

• What are the advantages and disadvantages of inactivated toxoid vaccines?

Answer 6

Adv:

Cheap

Well characterised

Safe 

Dis: 

Requires good understanding of biology of infection

Not all organisms encode toxins

Question 7

• Explain the mechanism of recombinant protein vaccines

Answer 7

Surface antigen gene is isolated

    Insertion into gene of 
another substance (e.g. yeast for Hep B virus)

Modified cell produces vaccine

Question 8

• What are most bacteria coated by?

- What are bacterial coats not very good at inducing?

Answer 8

Bacterial coats → capsule often made of polysaccharide (sugar)

B cell responses (it is a T independent antigen) which induces classic neutralising antibodies in the body

Question 9

• Describe the structure of a conjugate vaccine?

Answer 9

Polysaccharide coat component is coupled to an immunogenic “carrier” protein

Question 10

• What is the basic mechanism of a conjugate vaccine?

- Are the antibodies produced by the B cell against the polysaccharide or the protein part of the conjugated vaccine?

Answer 10

Protein enlists CD4 help to boost B cell response to the polysaccharide

Polysaccharide
As this is the molecule that they were activated by

Question 11

• Give an example of a dead pathogen vaccine

- What is a dead pathogen vaccine?

Answer 11

Influenza split vaccine

Chemically killed pathogen

Question 12

• What is the mechanism of dead pathogen vaccines?

Answer 12

Induces antibody and T cell responses

Question 13

• How are pathogens attenuated?

- Explain the mechanism of live attenuated vaccines

Answer 13

Serial passage (the process of growing bacteria or a virus in iterations) For instance, a virus may be grown in one environment, and then a portion of that virus population can be removed and put into a new environment → leads to loss of virulence factors

Replicate in situ triggering the innate response and boosts the immune response

Question 14

• Define adjuvant

- What is the function of adjuvants?

Answer 14

Substances used in combination with a specific antigen that produced a more robust immune response than the antigen alone

Induce danger signals that activate dendritic cells to present antigen to T cells

Question 15

• Outline the mechanism of an adjuvant

Answer 15

Stimulates DC

DC uptakes antigen and moves to lymph node 

Upregulates stimulatory signalling and cytokines

Question 16

• What does Alum do?

Answer 16

Stores the antigen at the site of injection and enables DC to see more of it and may induce some inflammation

Question 17

What are the phases of a clinical trial?

Answer 17

Pre-clinical

Phase 1 - safety in humans

Phase 2 - mixture of safety and efficacy studies

Phase 3 - shown to be safe and effective

FDA review (MHRA in UK) - licensing

Phase 4 - licensed and approved → then goes into large groups of people + more monitoring

Question 18

What are characteristics of an ideal vaccine?

Answer 18

Cheap

Easy to administer

completely safe

active against all variants

lifelong protection

single dose

stable

Question 19

what are the advantages of a recombinant protein vaccine?

what are the disadvantages?

Answer 19

Pure, safe

expensive, not very immunogenic (eg bacteria with polysaccharide coat)

Question 20

what are the advantages of conjugate vaccines

what are the disadvantages?

Answer 20

good for bacterial infections, highly improves immunogenicity

expensive
carrier protein may interfere
very strain specific
polysaccharide alone is poorly immunogenic

Question 21

what are the advantages of dead pathogen vaccine

what are disadvantages?

Answer 21

cheap, quick, inclusion of other components so highly immunogenic
antigenic components are left intact

fixing/ killing pathogen may alter antigen
quite "dirty"
requires capacity to grow pathogen
vaccine induced virulence it a risk
could be contaminated with live pathogen

Question 22

what are the advantages of a live attenuated vaccine?

what are the disadvantages?

Answer 22

strong immune response, can induce a local immune response at the site of infection

can revert to virulence
affects the immunocompromised
attenuation can lose antigens
can be outcompeted by other infections

Question 23

why is there need for new vaccines

Answer 23

Changing demographics (aging)

Changing environment (dengue)

new diseases

Old diseases we can’t fix eg HIV

antibiotic resistance

Question 24

What are the barriers to future vaccines

Answer 24

time taken to develop

cost of production

scientific challenges

injection safety

logistics

public expectation for a risk free vaccine

Question 25

what are the considerations when scheduling a vaccine

Answer 25

cost

availability

cultural attitudes and practices

facilities available for delivery

aim and need of the vaccine

scheduling other vaccines

population accessibility

Question 26

how are vaccines introduced to the UK

Answer 26

recommendations for a vaccine policy 
vaccine policy decisions
license vaccine
purchase vaccine
control of vaccine (including batch release)
post licensure assessment and changes