4.11 - Vaccination Flashcards

1
Q

What is a vaccine?

A
  • something that stimulates the immune system without causing serious harm or side effects
  • the aim of the immunisation is to provoke immunological memory to protect individuals against a particular pathogen if they later encounter it
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2
Q

What are the features of the ideal vaccine?

A
  • completely safe
  • easy to administer
  • single dose, needle-free (higher chance people take)
  • cheap
  • stable (so can move between site of manufacture and site of administration properly)
  • active against all variants
  • lifelong protection
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3
Q

How do vaccines stop infection?

A
  • vaccination is the generation of immune memory in the absence of harmful infection
  1. prevention of entry of pathogen into cells through antibodies
    - bind to virus and neutralise it to stop it from ever infecting cells in the first place
    - opsonisation of the virus that leads to macrophages engulfing it - driven by Fc on AB
  2. boosting immune response - antigens in vaccine will be recognised by CD4 T cells in context of MHC II –> these cells boost immune response e.g. train CD8 T cells to kill infected cells, working with B cells to make antibodies
  3. enables killing of infected cells
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4
Q

What kind of intervention are vaccines?

A

Population, not individual

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5
Q

What is R0?

A
  • basic reproduction number
  • the number of cases one case generates on average over the course of their infectious period
  • if R0 < 1 the infection will die out in the long run
  • if R0 > 1 the infection will be able to spread in a population
  • R0 can change - depends on population behaviour
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6
Q

How do vaccines reduce R0?

A
  • more vaccinated people in the population
  • less chance of an infected person meeting a susceptible unvaccinated individual to pass on the virus –> decreases R0
  • herd immunity - when a large percentage of the population is vaccinated, it makes it harder for the virus to spread to susceptible individuals as they are protected indirectly by vaccinated individuals
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7
Q

What is in a vaccine?

A
  • antigen - in one of these forms:
    1. inactivated protein e.g. tetanus toxoid
    2. recombinant protein e.g. hep B
    3. live attenuated pathogen e.g. polio / BCG
    4. dead pathogen e.g. split flu vaccine
    5. carbohydrate e.g. S. pneumoniae
  • adjuvant - normally alum, sometimes something proprietary
  • stabilising stuff (buffers - PBS)
  • water
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8
Q

What are the five classes of vaccine used in the UK?

A
  • inactivated toxoid vaccine
  • recombinant protein vaccine
  • conjugate vaccine
  • dead pathogen vaccine
  • live attenuated vaccine
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9
Q

What is an inactivated toxoid vaccine?

A
  • e.g. tetanus toxoid
  • vaccine has a chemically inactivated form of toxin - no longer toxic
  • 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
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10
Q

What is a recombinant protein vaccine?

A
  • e.g. hep B surface antigen
  • recombinant protein from pathogen
  • the gene from one organism is isolated and moved into a different organism –> protein is mass produced
  • induces classic neutralising antibodies that combine the protein and stop the virus getting into cells
  • advantages: pure, safe
  • disadvantages: relatively expensive, not very immunogenic, has not proved to be the answer to all pathogens (protein structure affects this)
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11
Q

How does protein structure affect recombinant protein vaccine?

A
  • e.g. RSV has a spike protein on its surface with two different forms - prefusion and postfusion (after it has bound to cell - this is how the virus injects its contents into cell)
  • vaccines are made for the prefusion structure but the proteins in the vaccine lapse into the second structure, which if injected, will make the wrong-shaped antibodies so the body won’t be able to see the virus properly so you don’t get immunised against the virus
  • this issue happens with many viruses and can be solved but you need to be aware of it
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12
Q

What is the issue when it comes to bacteria with inactivated toxoid vaccines and recombinant protein vaccines?

A
  • work well for protein antigens but bacteria often have a polysaccharide capsule surrounding them, not protein
  • this is not good at inducing a B cell response (it is a T independent antigen)
  • alternative approaches needed
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13
Q

What is a conjugate vaccine?

A
  • e.g. S. pneumoniae
  • vaccine is a polysaccharide coat component that is coupled to an immunogenic ‘carrier’ protein i.e. a sugar molecule stuck to a protein molecule, which B cell recognises
  • protein enlists CD4 help to boost B cell response to the polysaccharide
  • DC engulfs the whole antigen and presents the protein part onto MHC II - a B cell takes up the polysaccharide
  • TfH primed by DC through interacting with the DC’s MHC II presented peptide and then goes to the matching B cell and boosts it
  • B cells produce 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
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14
Q

What is a dead pathogen vaccine?

A
  • e.g. influenza split vaccine
  • rather than using a single antigen, it is 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 components, cheap, quick
  • disadvantages: fixing/killing can alter chemical structure of antigen, quite ‘dirty’, requires the capacity to grow the pathogen, vaccine induced pathogenicity a risk, risk of contamination with live pathogen
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15
Q

What is a live attenuated vaccine?

A
  • e.g. BCG, live attenuated influenza vaccine, OPV
  • pathogens are attenuated by serial passage - leads to a loss of virulence factors = virus looks the same but cannot cause damage
  • because they replicate in situ, 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
  • disadvantages: can revert to virulence, can infect immunocompromised, attenuation may lose key antigens, can be competed out by other infections
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16
Q

What is an adjuvant?

A
  • they are substances used in combination with a specific antigen that produce a more robust immune response than the antigen alone
  • induce ‘danger signals’ that activate dendritic cells to present antigen to T cells
  • part of licensing the response
  • alum stores the vaccine at site of injection which enables the DCs to see more of it = inflammation
17
Q

Why do we need new vaccines?

A
  • changing (aging) demographics - some infections aren’t severe in young adults but are for elderly
  • changing environment (dengue / other arboviruses)
  • new diseases (COVID-19)
  • old diseases we still can’t fix (HIV/TB/malaria)
  • antibiotic resistance (MRSA, all bacteria)
18
Q

What are some barriers to future vaccine development?

A
  • scientific challenges
  • injection safety - don’t want to spread secondary infection by sharing needles
  • logistics / cold chain - easy for high income countries to get vaccination but harder for LICs
  • development issues - time (15 years), cost of vaccine development high, cost of the product
  • public expectation of risk-free vaccines
19
Q

What kinds of pathogens make it harder for traditional vaccines to combat?

A
  • traditional vaccines effecting at eliciting humoral responses and are protective against invariant pathogens
  • however, the more diversity in the pathogen, the less protective - many circulating viruses and classic immune memory only recognises one of these strains and therefore vaccine antigens need to cover all the variety
  • serotype - one viral strain recognised by one family of antibodies
20
Q

What are the phases of a clinical trial?

A
  • preclinical - lab, hypothesis testing, vaccine developed
  • drug approved for testing in humans
  • phase 1 - 20-80
  • phase 2 - 100-300
  • phase 3 - 1000-3000
  • drug submitted for FDA approval
  • FDA review to confirm safety and effectiveness
  • drug approved
  • phase 4 - 1000+
21
Q

What are the steps and organisations involved in introducing new vaccines in the UK?

A
  • recommendations for vaccine policy - Joint Committee on Vaccination and Immunisation (JCVI)
  • vaccine policy decisions - department of health (DH)
  • licensing of vaccine - Medicines and Healthcare products Regulatory Agency (MHRA)
  • purchase of vaccine - DH from pharmaceutical companies
  • control of vaccine (including batch release) - National Institute for Biological Standards and Control (NIBSC)
  • post license assessment and changes - PHE/JCVI (epidemiology, assessment, trials)
22
Q

What are the considerations for scheduling vaccines?

A
  • aim
  • need
  • scheduling with other vaccines
  • availability
  • cost
  • population accessibility
  • cultural attitudes and practices
  • facilities available for delivery