Lecture 31 - Vaccination I Flashcards

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1
Q

Compare the terms vaccination and immunisation

A
  • Vaccination: deliberate induction of immunity by administration of vaccine
  • Immunisation: process by which an individual is made immune to a disease
  • Vaccination leads to immunisation
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2
Q

Compare the terms antigen and immunogen

A
  • **Immunogen: **a molecule that induces an immune response
  • **Antigen: **a molecule that is the target of an immune response
  • Not all antigens are immunogens
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3
Q

Who performed the first vaccination?

When?

How?

A
  • Edward Jenner
  • End of 1700’s
  • Smallpox vaccination
    • ​Observed that milkmaids did not die from smallpox
      • Milkmaids exposed to cowpox (vaccinia) and developed immunity to it
    • Hypothesised that immunity to cowpox prevented severe disease to smallpox (variola)
    • Vaccinated James Phelps with vaccinia
    • Boy protected from ‘repeated deliberate’ attempts to infect with Variola
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4
Q

Who characterised the mechanism of vaccination?

A
  • Louis Pasteur, 1880’s
  • Developed vaccines for:
    • ​Rabies
    • Anthrax
  • By deliberately attenuating the organisms
    • As opposed to Jenner, who had to find a less virulent form of the pathogen
  • Vaccination with the attenuated form protected against the more virulent, wild type form
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5
Q

What is the vaccine schedule?

A
  • Schedule of the various vaccines that should be given to individuals at various ages
  • Birth to 4 years: intensive schedule
    • ​HepB
    • Diphtheria
    • Tetanus
    • Poliomyelitis
    • Rotavirus
    • Pneumococcus
    • H. influenzae
    • Measles, Mumps, Rubella
    • Varicella zoster
    • etc.
  • At risk groups:
    • Aboriginal, Torres Strait Island populations
      • Live in areas with endemic Pneumococcus
    • Pregnant women
      • ​Influenza
    • Elderly:
      • ​Influenza
      • Pneumococcus
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6
Q

How do vaccines decrease disease in a population?

A
  1. Induce immunological memory: long lived immunity against a pathogen
    • ​​At the level of the individual
    • eg. Diphtheria vaccine
  2. Provide herd immunity
    • At the level of the population
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7
Q

Describe immunological responses to vaccination

A

B cell responses

  • Vaccination:
    • Stimulates IgM and IgG (specific for antigen) production
    • Low affinity initially, then higher affinity IgG
    • Titre remains high over time
  • Upon reinfection / boost:
    • IgG levels rapidly increase to provide protection

T cell responses

  • Vaccination:
    • Stimulates generation of a T cell response
    • Proliferation of the cells in the system
    • Differentiation into various T cell subtypes
    • Formation of a pool of memory cells
  • Upon reinfection / boost:
    • Memory cells rapidly are reactived
    • Increased magnitude of response (compared to primary response)
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8
Q

Describe herd immunity

A

Limitation of the ability of the pathogen to spread within a population

Only applies to diseases which are spread human-human

  • Pathogens with a zoonotic origin can persist even after everyone is vaccinated
  • Within a unvaccinated population:
    • When one individual becomes infected with a pathogen, it will likely be transmitted to a number of other individuals
    • Probability of coming across another unvaccinated individual is high
    • The pathogen spreads
  • Within a vaccinated population:
    • ​When one individual becomes infected, it cannot be transmitted, as the others are vaccinated
    • The spread of the pathogen is limited
    • Chance of coming across another unvaccinated individual is low
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9
Q

List factors that influence herd immunity

A
  • Environmental factors
    • ​Crowding
  • Infectivity of disease
    • ​Severity & symptoms
      • If the symptoms are severe, the person is more likely to isolate themselves
      • Sub-symptomatic disease: individual may still go to work etc. and spread the disease
  • Rate of spread
    • ​ie areas of high/low vaccine uptake
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10
Q

Describe Ring Vaccination

A

Use of herd immunity to contain an outbreak

  • Performed when it is not possible to vaccinate everyone
  • Scenario:
    • A particular community is infected
    • Quarantine of infected individuals from non-infected
    • Surrounding communities are vaccinated
    • Prevents the spread of the pathogen to the surrounding communities
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11
Q

What is Ebola?

Describe the 2014 Ebola outbreak

A
  • Emerging, highly virulent virus
    • 50% mortality rate
  • Causes **viral **haemorrhagic fever
    • Internal and external bleeding
    • Ultimately leads to multiple organ failure
  • 2014 outbreak:
    • Outbreak in West Africa
      • Sierra Leone, Guinea, Liberia
    • ​Largest outbreak to date
    • Currently 4,000 deaths
    • Predicted 20,000 deaths by the end of the year
    • Factors causing spread:
      • No vaccine
        • Still needs to be trialled for safety & efficacy, will take some time
      • No accessible/viable treatments
        • mAb therapy: expensive & difficult to manufacture
      • Long incubation period → high transmissability
        • 21 days from infection for the disease to manifest
      • Mistrust
      • Cultural practices
      • Hygeine standards in these countries
    • This is a situation where ring vaccination would be beneficial
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12
Q

Why are we seeing re-emergence of infectious diseases for which we have effective vaccines?

A
  • Parents are not allowing their children to be vaccinated
    • Because we don’t see infectious diseases in the first world, people think that there is no risk
    • Through fear of autism from vaccination
  • Herd immunity works when up to 95% of the population is covered
  • Measles, Whooping cough
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13
Q

What is an ‘ideal vaccine’?

A

Induces the same quality of immunity as would an infection with the natural pathogen

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14
Q

What are adjuvants?

List a few

How do they work?

A
  • Substance that hepls increase immunogenicity of a co-administered vaccine
    • Some vaccines have low immunogenicity → adjuvant is required
    • Others do not require them
  • Examples
    • ​Freunds complete adjuvant
      • ​Very strong
      • Toxic
    • Aluminium-based adjuvants
      • ​Safe
      • Adjuvant of choice for many clinically used vaccines
      • Limited by ability to induce particular types of immune responses:
        • ​Good neutralising Ab
        • Poor cell-mediated responses
    • Montanide water-in-oil formulations
      • ​Good immunogenicity
  • MOA
    • ​Stimulate pro-inflammatory responses
    • Provide a depot of Ag
      • ​Slow release of Ag
  • Drawbacks
    • Make simple concoctions more complex
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15
Q

List some types of vaccine

Give examples of each

A
  • Live attenuated
    • ​Vaccinia
    • BCG
    • MMR
    • Sabin poliovirus vaccine
  • Inactivated
    • ​Salk
    • Various influenza subtypes
  • Subunit
    • ​HepB surface Ag (HBsAg)
    • H. influenzae type b
      • ​Polysaccharide-protein conjugate
    • Bordetella pertussis Ags
    • Diphtheria toxoid
    • Tetanus toxoid
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16
Q

Describe live attenuated vaccines

A
  • Weakened pathogen
  • Some level of replication & pathogencitiy → stimulate immunity without causing disease
  • Advantages
    • ​Do not require adjuvants or boosters
  • Disadvantages
    • ​Risk for immunocompromised individuals
    • Mutations are not well characterised
    • Reversion to WT pathogen
      • ​Due to too few mutations
    • Attenutation results in mutations that limit replication and pathogenicity
17
Q

Describe inactivated vaccines

A
  • All antigens present
  • Virus cannot replicate or infect
  • Advantages
    • ​Safer
  • Disadvantages
    • ​Requires boosters & adjuvants
    • Risk if the inactivation vaccine is not complete
18
Q

Describe subunit vaccines

A
  • Only antigen is used
  • Virulent components aren’t present
  • Advantages
    • ​Safer
    • Better characterised
  • Disadvantages
    • ​Not usually immunogenic → requires adjuvant (Alum)
    • Requires multiple boosters
19
Q

Against which sorts of pathogens are vaccines most effective?

A
  • Short incubation period
  • No animal reservoir
  • Human-human transmission
  • Identifiable clinical symptoms
  • Little or no variation in pathogen
    • ​ie not influenza
20
Q

Describe the disease and eradication of Smallpox (Variola)

Why was this campaign so effective?

A
  • Smallpox disease
    • ​Appearance of painful pustules all over the body, respiratory tract, stomach
    • Been around for thousands of years
    • Caused 300-500 deaths
    • 1 in 4 mortality rate
  • Eradication programme
    • ​Launched in 1967 by WHO
    • Ring vaccination
    • Eradicated in 1979
    • No outbreaks since
  • Effectiveness of vaccine
    • ​No mutation in Ags of Variola
      • Vaccine remains effective
    • Ab titres remain high for many years
    • T cell response is very long lasting
      • ​15-30 years
    • N° of vaccinations does not affect the effectiveness of the response
      • ​No need for boosters
21
Q

Describe the disease and eradication of Poliovirus

A
  • Poliovirus:
    • ​Causes poliomyelitis
    • Can destroy neurons in the CNS
    • Individuals stop breathing
  • Salk vaccine
    • 1955
    • ​Formalin inactivated poliovirus
    • Injected
    • Risk of inadequate inactivation
  • Sabin vaccine
    • ​1961
    • Second generation vaccine
    • Attenuated virus strain
    • Oral administration
    • 3 viral serotypes
    • Reversion to WT
      • ​1 in 3 million vaccinations
      • 2005: in many countries, switch to IPV from OPV
  • Eradication
    • ​Both of these vaccines work very well to reduce spread of Polio
    • 1988: high incidence of polio throughout much of the world
    • 2009: Isolated to central Africa and India
    • 2013: Isolated to some African countries, Pakistan, Afghanistan
    • Eradication is imminent
22
Q

Describe disease and eradication of RSV

A
  • RSVU
    • LRTI in children
    • Great need for vaccine
  • Vaccine
    • ​Increased susceptibility to RSV infection
    • Worse disease than non-vaccinated children
    • Several children died from vaccination
    • Why?
      • ​Immune hypersensitivity response induced
        • ​Innapropriate TH2 response (instead of TH1)
23
Q

For which pathogens do we not have effective vaccines?

A
  • HIV
  • HCV
  • M. tuberculosis
24
Q

What is the benefit of oral administration of the Sabin polio vaccine?

A

Same route of transmission of WT pathogen

→ more appropriate immunity

25
Q

Compare advantages and disadvantages of the Salk and Sabin vaccines

A
  • Advantages
    • ​Salk
      • ​No cold chain required
      • Can’t revert to virulence
    • Sabin
      • ​Oral administration
      • Replicates: no boosters required
  • Disadvantages
    • ​Salk
      • ​Injection
      • Large quantities of virus are required
      • Boosters required
      • Risk of inadequate inactivation
    • Sabin
      • ​Cold chain required
      • Can revert to virulence in 1 in 3 million vaccinations
26
Q

Describe poliovirus vaccinatino in Australia

A
  • In countries where poliovirus infection is now very low, the risk of the Sabin vaccine (revert to WT in 1 in 3 million doses) is not acceptable
  • In 2005, the Sabin (OPV) was replaced with a modified inactivated vaccine (IPV)