Vacccinations Flashcards
Vaccine
Something that stimulates the immune system without causing serious harm or side effects
Features of an ideal vaccine
- 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
How do vaccines stop infection
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
R0
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
Rt value
Alteration of R0 value due to vaccination
What is in vaccines
Antigens
Adjuvants
Stabilizing stuff eg buffers
Residual traces eg formaldehyde
Water
What form can the antigens be In
- 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
Adjuvants
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
Mechanism of adjuvant
Stimulates DC
DC uptakes antigen and moves to lymph node
Upregulates stimulatory signalling and cytokines
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Inactivated toxoid vaccine
- 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
Recombinant protein vaccine
- 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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What is this issue with inactivated toxoid vaccines and recombinant protein vaccines
Works well for protein antigens but bacteria have a polysaccharide capsule surrounding them which doesn’t induce a B cell response
Conjugate/carbohydrate vaccines
- 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
Dead pathogen vaccines
- 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
Live attenuated vaccines
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
