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Flashcards in Scientific Basis of Vaccines Deck (26)
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1

What is the definition of a vaccine? 

  • A vaccine is material from an organism that actively enhances adaptive immunity 
    • It produces an immunologically primed state which will allow for rapid secondary immune response on exposure to an antigen causing DISEASE prevention (but not infection) 

2

In what kind of state is a the body in following vaccine administration. 

 

 

A vaccine will produce an immunologically primed state which will allow for a rapid secondary immune response on exposure to an antigen 

  • We need it to prevent disease but not infection 
    • By this we mean we need the vaccine to protect us from example bacterial toxins e.g tetanus 

3

How did vaccines come about? 

  • People were infected with small pox virus (variola) 
  • Found that people could become immunised against small pox through variolation 
    • Variolation = scabs were taken from previously infected people and would be inserted into the skin of other patients through superficial scratches producing a less severe disease, after a few weeks of suffering less severe symptoms they would develop immunity 
  • It was discovered that milkmaids who contracted cow pox (vaccinia virus) would not get small pox and would not be variolated as they didnt recieve lesions on their arm 
  • Edward Jenner discovered that the mild cowpox virus conferred immunity against the deadly smallpox virus 
    • This was developed into a vaccine 

4

What is the rationale behind vaccines? 

Vaccines serve two purposes 

  1. Protect individuals from disease 
  2. Protect populations 
    • Vaccination are a public health intervention, the aim of a vaccine is to achieve herd immunity, if the virus is still present we can make vulnerable members of society susceptible to the disease 

5

What scientific concepts were discovered from the discovery of the smallpox vaccine? 

  1. Challenge dose – proves protection from infection
  2. Concept of attenuation
  3. Concept that prior exposure to agent boosts protective response
  4. Cross-species protection – antigenic similarity (revolutionary to think that a virus from cows could be used to protect against a human virus)

6

How was smallpox eradicated? 

  • Vaccination programmes (would vaccinate everyone who came into contact with someone who contracted smallpox)
  • Case finding (surveillance)
  • And movement control (stopped people migrating from areas where there was a case of smallpox)

7

Why was it possible to eradicate smallpox? 

  • There were no sub-clinical infections of the variola virus (no asymptomatic carriers who shed the virus)
  • After recovery, the virus was eliminated – no carrier states (latency, reactivation, shedding)
  • No animal reservoir
  • Effective vaccine (live vaccinia virus)
  • Slow spread, poor transmission

8

Explain the vaccination paradox 

  • If you vaccinate more people, and there is less infectious pool in the community then you will not have natural boosting 
    • Natural boosting = Boosting of your immune system via exposure to infections in the community. 
      • You may not see the disease again, however your immune system is familiar with it and will have antigens ready 
  • Thus we need to ensure vaccine uptake rates stay high, because as soon as they drop we may see an increase in the disease 

9

What are the two types of immunity? 

Active and Passive 

Active Immunity 

  • We can enhance this natural exposure (carriage), infection or vaccination and is long term 

Passive Immunity 

  • Antibody administration from another serum source for prophylaxis and/or treatment 
    • E.g post exposure protection in rabies + vaccin, this is because the incubation period is so long, anti-tetanus horse serum used to treat many soldiers 

10

What are the immune responses to antigens? 

PRIMARY EXPOSURE 

  • Will take about 5-7 days for an antibody response 
  • 2 weeks for a full response 
  • IgM to IgG class switching, memory B andT cells 

SECONDARY RESPONSE (prior exposure) 

  • Takes 2 days for a full protective response 

11

What considerations do we need to think of when developing a god vaccine? 

  1. Will it induce the correct TYPE of response (antibodies vs CMI)
  2. Induce the response in the RIGHT PLACE (sIgA vs IgG) 
  3. How long is the duration of protection from this vaccine? (Do we need boosters to maintain long term immunity) 
  4. What is the incubation period of the infection? (short incubation period diseases are less likely to be effective using vaccinations) 
  5. Age of vaccination (maternal antibodies in neonate, live attenuated vaccines will be inactivated by residual immunity) 
  6. Safety precautions (insufficient attenuation, reversion to viruelence, allergic reactions) 

12

Why is it important to induce the correct TYPE of response with a vaccine? 

  • Do we want the cell mediated immunity or antibody response? 
    • For infections in the blood or mucosal surface antibodies will be sufficient 
      • SIgA = mucosal, IgG = polio 
    • Some infections will infect inside cells e.g tuberculosis or virus and for these we will need to drive T cell immunity 

13

Why is it important to induce a response in the RIGHT place? 

  • Polio and influenza colonise at mucosal surfaces therefore we will need good protective immunity at our secretory surface
    • (sIgA response) 
  • Systemic infections (yellow fever) we will need an immune response in the bloodstream for example IgM and IgA
    • Parenteral vaccines → poor mucosal immunity
    • Oral vaccines→ processed by MALT, good IgA

14

Describe why the incubation period is important when developing a vaccine, and why boosters are also important. 

  • Long incubation time – systemic (measles)
    • This allowstime for increased residual immunity before onset of disease 
  • Short incubation time – surface (cholera)
    • Poor residual immunity and microbes grow too quickly, vaccinations are ineffective 
  • Boosters - we need long term immunity, we can maintain this through boosters, these can be acquired naturally or through vaccines 

15

Why is the age of vaccination important? 

  • Babies when they are new-born have high maternal antibodies
    • sIgA in milk
  • We can’t use live attenuated vaccines e.g. MMR until the maternal antibodies have dropped!! This is because the maternal antibodies will neutralise the virus and there will be no protection due to passive transfer
  • We are able to vaccinate at around 9 months,
    • However we can also use this to our advanatge and vaccinate mothers to allow for passive transfer, for example protection against neonatal tetanus, whooping cough, flu

16

Why do we have to consider the nature of the antigen when developing a vaccine? 

  • Monotypic infections (e.g measels) = There is no difference in the antigenic nature 
  • Polytypic infections (e.g influenza, gonorrhoea) = Highly variable in their antigens, most vaccines are not cross protective to different strains of the same pathogen 

ALSO 

  • Most antigens are immunogenic but not immune-protective (unless they are surface components which can prevent it from adhering or neutralising its toxins) 
  • Serology can differentiate exposure from vaccination 

 

17

What are the three types of vaccines? 

  1. Live attenuated organism 
  2. Killed, Whole Organism 
  3. Subunit Vaccine 

18

Describe live attenuated organism vaccines? 

  • They can be modified through serial passage, low temperature adaptation, recombination genetics, selection of natural attenuated strains
  • Most of these do not require boosting (with the exception of a few for other reasons like treating both mild and severe rota virus) 
    • This is because the live vaccine will continually prime the immune response and give you that protection 
  • Examples BCG, MMR, yellow fever, VZV 

19

Describe killed whole organism vaccines 

  • Polio vaccine, cholera and HepA 
  • Single dose you get a slight immune response but not near enough level for immune protection therefore you need boosting due to reactogenicity 

20

Describe subunit vaccines? 

  • These are components of the pathogen which give you good protective immunity for example;
    • Proteins
    • Toxoids (diphtheria; tetanus)
    • Peptides (synthetic)
    • Polysaccharide
      • Poor antigens and need to be conjugated!!!
      • Conjugated to toxoid + outer membrane proteins (e.g MenC; Hib)
    • Recombinant proteins
    • Sub-cellular fractions
    • Surface antigens
      • E.g Hepatitis B; influenza haemagglutinins; menB
    • Virulence determinant
      • E.g aP-pertussis;- adhesin + toxoid + OMP

21

Explain how bacterial toxins can work as vaccines

  • Bacterial toxins will normally cause direct tissue damage and disease 
  • The toxin can be purified an inactivated chemically to form a toxoid 
    • The toxoid is antigenic and non-toxic to us 
  • The toxoid will be used as a vaccine which can induce an antibody response 
    • If we become infected with the bacteria it will not be able to cause disease as the antibodies will neutralise toxins produced by the bacteria 

22

What are some examples of toxoid based vaccines? 

Diptheria, tetanus and whooping cough 

23

What is the issue with using bacterial capsular polysaccharides as vaccines? 

  • Poor antigens 
    • Short term memory, no T cell immunity 
  • Less immunogenic in children <2 years 
    • They have more poor IgG2 responses 
      • IgG2 will promote opsonisation and major recognition of polysaccharides 
  • This will enhance immunogenicity of bacterial capsular polysaccharide by protein conjugation 
    • Examples of this are Neisseria meningitidis Group C  (MenC vaccine), Haemophilus influenzae Type B (Hib Vaccine)

 

24

How do we enhance the immunogenicity of the polysaccharide capsule? 

  • The capsule is removed and linked to a carrier protein the infants immune system already recognises 
    • No carrier protein conjugation = The PS will bind to the B cell receptor + recognise it poorly 
      • Will not produce many PS specific antibodies 
    • With carrier protein conjugation = B cell will recognise this protein and present it to a T cell through MHC Class II. This will lead to the production of cytokines 
      • This encourages the production of PS specific antibodies from the B cell 

25

What are vaccine adjuvants? 

Chemical or lipid structures which enhance the immune response using vaccine components 

  • With adjuvants the antibody response is much higher 
  • They will trap antigens in vaccines and prevent them from being cleared as efficiently from defence mechanisms like macrophages 

26

Summarise the three main things that vaccine adjuvants do? 

What is an example of a vaccine adjuvant? 

  1. Enhance immune response to antigen 
  2. Promote uptake and antigen presentation 
  3. Stimulate correct antigen profiles 

Example = Aluminium Salts (Alum) 

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