vaccination Flashcards
- What is a vaccine?
- What is the aim of immunisation?
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
- What 3 main areas do vaccines work in?
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
- What is in a vaccination?
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
- Give an example of an inactivated toxoid vaccine
- Describe what is meant by an inactivated toxoid vaccine
Tetanus toxoid vaccination
Chemically inactivated form of toxin
- how does an active toxin work?
- Explain the mechanism of inactivated toxoid vaccines
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
- What are the advantages and disadvantages of inactivated toxoid vaccines?
Adv:
Cheap Well characterised Safe Dis: Requires good understanding of biology of infection Not all organisms encode toxins
- Explain the mechanism of recombinant protein vaccines
Surface antigen gene is isolated
Insertion into gene of another substance (e.g. yeast for Hep B virus)
Modified cell produces vaccine
- What are most bacteria coated by?
- What are bacterial coats not very good at inducing?
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
- Describe the structure of a conjugate vaccine?
Polysaccharide coat component is coupled to an immunogenic “carrier” protein
- 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?
Protein enlists CD4 help to boost B cell response to the polysaccharide
Polysaccharide As this is the molecule that they were activated by
- Give an example of a dead pathogen vaccine
- What is a dead pathogen vaccine?
Influenza split vaccine
Chemically killed pathogen
- What is the mechanism of dead pathogen vaccines?
Induces antibody and T cell responses
- How are pathogens attenuated?
- Explain the mechanism of live attenuated vaccines
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
- Define adjuvant
- What is the function of adjuvants?
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
- Outline the mechanism of an adjuvant
Stimulates DC
DC uptakes antigen and moves to lymph node Upregulates stimulatory signalling and cytokines
- What does Alum do?
Stores the antigen at the site of injection and enables DC to see more of it and may induce some inflammation
What are the phases of a clinical trial?
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
What are characteristics of an ideal vaccine?
Cheap
Easy to administer
completely safe
active against all variants
lifelong protection
single dose
stable
what are the advantages of a recombinant protein vaccine?
what are the disadvantages?
Pure, safe
expensive, not very immunogenic (eg bacteria with polysaccharide coat)
what are the advantages of conjugate vaccines
what are the disadvantages?
good for bacterial infections, highly improves immunogenicity
expensive
carrier protein may interfere
very strain specific
polysaccharide alone is poorly immunogenic
what are the advantages of dead pathogen vaccine
what are disadvantages?
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
what are the advantages of a live attenuated vaccine?
what are the disadvantages?
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
why is there need for new vaccines
Changing demographics (aging)
Changing environment (dengue)
new diseases
Old diseases we can’t fix eg HIV
antibiotic resistance
What are the barriers to future vaccines
time taken to develop
cost of production
scientific challenges
injection safety
logistics
public expectation for a risk free vaccine
what are the considerations when scheduling a vaccine
cost
availability
cultural attitudes and practices
facilities available for delivery
aim and need of the vaccine
scheduling other vaccines
population accessibility
how are vaccines introduced to the UK
recommendations for a vaccine policy vaccine policy decisions license vaccine purchase vaccine control of vaccine (including batch release) post licensure assessment and changes