Vacccinations

Question 1

Vaccine

Answer 1

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

Question 2

Features of an ideal vaccine

Answer 2

• Cheap
• Completely safe
• Easy to administer so can be given to many people quickly
• Single dose, needle-free → not always doable but is ideal to make it quicker and so higher chance more people will take them i.e. no fear of needles
• Stable so can move between site of manufacture and site of administration properly
• Active against all variants e.g. with influenza the virus changes every year so new vaccine needed
• Life-long protection so you get immunised at birth and are protected for life

Question 3

How do vaccines stop infection

Answer 3

Prevent entry of pathogen into cell:

1) bind to virus and neutralise it to stop it from ever infecting cells in the first place

2) Opsonisation of the virus that leads to macrophages engulfing it → driven by constant region on antibody
Booster immune response:
Antigens in vaccine activate CD4 T cells

Enables killing of infected cells:
CD4 triggers CD8 T cells and activate B cells to make Ig

Question 4

R0

Answer 4

Is the reproduction number
The number of cases one case generates in average
R0<1 infection dies in long run
R0>1infectiin can spread and expand in population

Question 5

Rt value

Answer 5

Alteration of R0 value due to vaccination

Question 6

What is in vaccines

Answer 6

Antigens
Adjuvants
Stabilizing stuff eg buffers
Residual traces eg formaldehyde
Water

Question 7

What form can the antigens be In

Answer 7

• Inactivated protein e.g. tetanus toxoid
• 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

Question 8

Adjuvants

Answer 8

a substance which enhances the body’s immune response to an antigen.
Alum is usually used in vaccines-it stores the antigen at the site of injection and enables DC to see more of it
Induce danger signals that activate dendritic cells

Question 9

Mechanism of adjuvant

Answer 9

Stimulates DC

DC uptakes antigen and moves to lymph node

Upregulates stimulatory signalling and cytokines

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Question 10

Inactivated toxoid vaccine

Answer 10

• e.g. tetanus toxoid → vaccine has chemically inactivated form of toxin
• The vaccine induces antibody which blocks the toxin from binding to cells (nerves in tetanus’ case)
• Advantages: cheap, well characterised safe, in use for many decades
• Disadvantages: requires good understanding of biology of infection & not all organisms encode toxins

Question 11

Recombinant protein vaccine

Answer 11

• e.g. hep B surface antigen
• The gene from 1 organism is isolated and moved into a different organism. Protein is mass produced e.g. with hep B it is its surface antigen, which is then injected into body
• This vaccine induces classic neutralising antibodies that combine the protein and stop the virus getting into cells
• Advantages: Pure, safe
• Disadvantages: relatively expensive, not very immunogenic (work much better with adjuvant though), has not proved to be answer to all pathogens

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Question 12

What is this issue with inactivated toxoid vaccines and recombinant protein vaccines

Answer 12

Works well for protein antigens but bacteria have a polysaccharide capsule surrounding them which doesn’t induce a B cell response

Question 13

Conjugate/carbohydrate vaccines

Answer 13

• e.g. S. pneumoniae
• The vaccine is a polysaccharide coat component that’s coupled to an immunogenic ‘carrier’ protein i.e. a sugar molecule stuck to a protein molecule
• A DC engulfs the whole antigen and presents the protein part onto MHCII. A B cell takes up the polysaccharide part of the antigen and presents it onto its MHCII
• Tfh is primed by DC through interacting with the DC’s MHCII presented peptide and then goes to the matching B cell (presenting the same thing) and boosts it
• B cells produces a lot of anti-sugar antibodies
• Advantages: Improves immunogenicity, highly effective at controlling bacterial infection
• Disadvantages: cost, carrier protein interference, very strain specific, polysaccharide alone is poorly immunogenic

Question 14

Dead pathogen vaccines

Answer 14

• e.g. influenza split vaccine
• Rather than using a single antigen, it’s a chemically killed pathogen
• This induces antibody and T cell responses
• Advantages: Leaves antigenic components intact and in context of other antigen. Immunogenic because of the inclusion of other component. Cheap and quick
• Disadvantages: Fixing/killing can alter chemical structure of antigen, quite ‘dirty’, requires the capacity to grow the pathogen e.g. H5N1, vaccine induced pathogenicity a risk, risk of contamination with live pathogen (polio), not happened since 1953

Question 15

Live attenuated vaccines

Answer 15

e.g. BCG, Live Attenuated Flu Vaccine (LAIV), Polio vaccine
Serial passage attenuated pathogens as it leads to loss of virulence factors

• Because they replicate in situ infections they trigger the innate response and boost the immune response
• Advantages: Induce a strong immune response. Can induce a local immune response in the site where infection might occur (e.g. LAIV)
• Disadvantages: Can revert to virulence, can infect immunocompromised (BCG/HIV), attenuation may lose key antigens, can be competed out by other infections e.g. if you give polio vaccine to someone with a gut infection you’re less likely to get a good immune response

Question 16

Why do we need new vaccines

Answer 16

Changing demographics
Changing environment
New disease
Old disease
Antibiotic resistance

Question 17

Development issues

Answer 17

• Time taken to develop a new vaccine has gone from 8 years in 60s to 15 years now
• Cost of vaccine development is high
• Cost of the product