Lecture 31 - Vaccination I

Question 1

Compare the terms vaccination and immunisation

Answer 1

• 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

Question 2

Compare the terms antigen and immunogen

Answer 2

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

Question 3

Who performed the first vaccination?

When?

How?

Answer 3

• 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

Question 4

Who characterised the mechanism of vaccination?

Answer 4

• 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

Question 5

What is the vaccine schedule?

Answer 5

• 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

Question 6

How do vaccines decrease disease in a population?

Answer 6

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

Question 7

Describe immunological responses to vaccination

Answer 7

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)

Question 8

Describe herd immunity

Answer 8

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

Question 9

List factors that influence herd immunity

Answer 9

• 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

Question 10

Describe Ring Vaccination

Answer 10

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

Question 11

What is Ebola?

Describe the 2014 Ebola outbreak

Answer 11

• 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

Question 12

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

Answer 12

• 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

Question 13

What is an ‘ideal vaccine’?

Answer 13

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

Question 14

What are adjuvants?

List a few

How do they work?

Answer 14

• 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

Question 15

List some types of vaccine

Give examples of each

Answer 15

• 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

Question 16

Describe live attenuated vaccines

Answer 16

• 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

Question 17

Describe inactivated vaccines

Answer 17

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

Question 18

Describe subunit vaccines

Answer 18

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

Question 19

Against which sorts of pathogens are vaccines most effective?

Answer 19

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

Question 20

Describe the disease and eradication of Smallpox (Variola)

Why was this campaign so effective?

Answer 20

• 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

Question 21

Describe the disease and eradication of Poliovirus

Answer 21

• 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

Question 22

Describe disease and eradication of RSV

Answer 22

• 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 T_H2 response (instead of T_H1)

Question 23

For which pathogens do we not have effective vaccines?

Answer 23

• HIV
• HCV
• M. tuberculosis

Question 24

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

Answer 24

Same route of transmission of WT pathogen

→ more appropriate immunity

Question 25

Compare advantages and disadvantages of the Salk and Sabin vaccines

Answer 25

• 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

Question 26

Describe poliovirus vaccinatino in Australia

Answer 26

• 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)