SPR L13 Vaccinations and Immunotherapy 1 Flashcards Preview

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Flashcards in SPR L13 Vaccinations and Immunotherapy 1 Deck (27):

Learning Outcomes 


  • Approaches to control of infectious disease in populations
  • The requirements for a good vaccine.
  • Different types of vaccine and  the advantages and disadvantages of these.
  • The use of adjuvants.
  • Current vaccines in use and describe the UK vaccination schedule


Control of Infectious Disease in Populations

How can infectious diseases be limited?

by drugs, immunisation and a 'healthy' environment

  • By the use of drugs (chemotherapy).
  • By vaccines (immunisation).
  • By improving the environment (better sanitation, nutrition). 


Control of disease

  1. What do decisions depend upon?
  2. What can then be determined?
  3. Give an example of how clinical observation is important
  4. How are surveillance systems set up?

  1. ability to recognise outbreaks of disease, follow their progress and identify the causative organism
  2. where and how outbreak has arisen, who is at risk and what treatment is necessary to control further infection
  3.  e.g. discovery of AIDS in 1981 through increased occurrence of Pneumocystis jiroveci pneumonia.
  4. through government locally and through the World Health Organisation (WHO)- e.g  currently swine flu.


Control Versus Eradication

Eradication is always the ideal endpoint - what questions need to be asked?


What are important factors in eradication and control?

  • Which diseases could, with suitable effort, be eradicated?
  • Would the cost of eradication be justified?
  • Which diseases need urgent measures to stop them getting worse?
  • Which diseases are responsible for the most human suffering and economic loss?

Important Factors                                                                                    Disease limited to humans host 

  • Cases easily recognized clinically 
  • Surveillance possible
  • Stable, cheap, effective vaccine available
  • Worldwide programme possible
  • Eradication programme is cost-effective


To Control Infection Understanding the Biology of the Infectious Agent is Important

Hosts are 4 classes of individuals, name these


  1. susceptible;
  2. infected but latent (i.e. non-infectious);
  3. infected and infectious;
  4. recovered and immune 


To Control Infection Understanding the Biology of the Infectious Agent is Important

Recovery from infection usually gives what?

What are the exceptions?



immunity against re-infection; in case of viral infections, this may be lifelong. –

Exceptions (e.g. herpes, HIV, RSV)

For macroparasites immunity is short-lived.


Incubation, Latent and Infectious Periods

  1. What is the incubation period?
  2. What is the latent period?

  1. he phase before symptoms appear
  2. overlaps with incubation period- is non-infectious phase


Why Important to Understand the Reproductive Rates of Micro-organisms and Parasites

  1. What does the initual rate of increase of an infection depend upon?
  2. What is RO?
  3. What is herd immunity?

  1.  the magnitude of R0 (the basic reproductive rate).
  2. R0 is defined as the average number of secondary cases of infection produced by one primary case in a completely susceptible population. - The greater the value of R0 the greater the rate of increase.

Appearance of infections caused by organisms with a high R0 requires a rapid protective response at both the individual and community level. e.g. measles has a high R0 value (15-17).

3. Concept of herd immunity – level of immunity at which an infectious agent can no longer continuously circulate is related to R0


The Effective Reproductive Rate-R

The spread of infection is related to R0 the basic reproductive rate of the infectious agent. However susceptibility differs with...?


  • Sex 
  • Age
  • Genetics 
  • Nutritional and immunological status
  • Previous exposure;

Therefore a more actual reproductive rate is measured by the effective reproductive rate - symbol R.

Concept of herd immunity – level of immunity at which an infectious agent can no longer continuously circulate (R becomes <1)


Transmission Success

  1. What does this vary between? Why?

  1. Varies between communities because of differences in demography (net birth rate) and behavioural (patterns of mixing). e.g. inter-epidemic period for measles in large urban centres in Africa or India before the introduction of mass vaccination was often 1 year.

In the UK and the USA the period was typically 2 years.

Reflects difference in the average age at infection 



What is vaccination used to do?

Vaccination is used to protect individuals

  • Those exposed to infectious agents- in hospitals, laboratories etc
  • Tourists or military personnel travelling to areas where they encounter unfamiliar and serious infections.

To control or eradicate disease

  • The higher the rate of R0 the harder it will be to eradicate the infection. e.g. measles  (R0 15-17) will be more difficult to eradicate than smallpox was (R0 2-4).


Mass Vaccination Can have Indirect Disease Consequences

What are these?

  • Increases the average age at infection
  • Increases the inter-epidemic period.  
  • Affects the age distribution of cases and the pattern of fluctuations.


The Risks of Infection Must Outweigh any Risk Associated with Vaccination

Give examples of the age-dependent risk of complications from infection


  • Mumps
    • Vaccination reduces risk as complications increase with age- 20-30 year peak.
  • Measles (encephalitis)
    • Vaccination reduces risk and CNS complication s increase with age
  • Rubella
    • Vaccination can push the risk of rubella infection towards the child bearing years.


Means of infection Control in Populations other than Vaccines

Give examples of general measures that can be taken

  • Water purification (water-borne diseases)
  • Sewage disposal (enteric infections)
  • Hygeine, crowding, safe sex,
  • Animal reservoirs
  • Improved nutrition (host defense)
  • Improved housing (less crowding, dirt, etc.)
  • Screening (antenatal, blood transfusion etc) 


Means of infection Control in Populations other than Vaccines

Give examples of measures that can be taken in...

  1. Food
  2.       Zoonoses and arthropod-transmitted infections

  1. Cold storage 

    Pasteurization (milk, etc.)

    Food inspection (meat, etc.)

    Adequate cooking

  2. Control of vectors (mosquitoes, ticks, lice, etc.) Control of reservoir animal (rabies, bovine TB) 



  1. What should a vaccine contain?
  2. Give examples of vaccines used today

  1. should contain some (or at least one) of the protective antigens of the microbe.
  2. The vaccines in use today of different types, each advantages and disadvantages:
  • microbes with artificially reduced virulence ('attenuated') - weakened form. Can still be used to generate an immune response.
  • microbes with naturally reduced virulence for humans
  • killed organisms
  • subcellular fragments
  • Genetically engineered recombinant vaccines. 


Live Attenuated Vaccines

  1. Some of the attenuated virus vaccines in current use were produced by... 
  2. What are the two principal methods?
  3. Oral polio vaccine (OPV), attenuation was by...? 

  1. the selection of mutants induced at random - 'genetic roulette' 
  2. serial passage in cells cultured in vitro, adaptation to low temperatures.

  3. passage through monkey kidney cells or human embryo fibroblasts, virulence being checked for by signs of neurotoxicity in monkeys .

    Analogous methods have been used for measles, rubella, mumps and yellow fever 


Live Attenuated Vaccines 

Give examples


  • Oral Poliovirus (no longer used in UK)
  • Measles, Mumps, Rubella (MMR)
  • Yellow Fever
  • Rotavirus RRV- New in UK 2013
  • Varicella- USA –available to health care workers in UK
  • Shingles vaccine for >70years old New in UK 2013 (Shingles is the recurrence of chickenpox along a dermatone) Post repetic neuralgia in adults.
  • Live attenuated influenza vaccines for children –New UK 2013


Microbes with Naturally Reduced Virulence for Humans

Give examples

  • Vaccination with cowpox - prevented smallpox - Edward Jenner 1749-1823


  • 10 - 50% mortality, blindness, severe scarring
  • 18th centuary Europe 2-600,000 deaths annually
  • 1979 WHO declared Smallpox eradicated


Live Attenuated Virus Vaccines

What are the advantages and disadvantages?


  • Good immunogens - best vaccines
  • Induce long-lived, appropriate immunity
  • Tend to produce IgA and mucosal immunity
  • May offer alternative routes (e.g. oral)
  • Lasts a long time


  • Cold chain vital for live vaccines- labile
  • Potentially unstable genetically (possible reversion to virulence)
  • Not possible to produce in all cases - trial and error
  • Contamination possible (SV40) initially in poliovirus vaccine
  • Inappropriate/accidental vaccination to at risk groups (immunosuppressed and pregnant) may pose risk


Inactivated Vaccines

Give an example

One of the most famous inactivated vaccines, the rabies vaccine, dates back to the time of Pasteur (1885).

Pasteur used dried spinal cord from an infected rabbit


 Inactivated Vaccines

What are the advantages and disadvantages?


  • Stable
  • Little or no risk (if properly inactivated)


  • Not possible for all viruses; denaturation may lead to loss of antigenicity and adverse affects, e.g. measles, RSV.
  • Not as effective at preventing infection as live viruses (mucosal immunity - IgA).
  • May only protect for a short period protect


Sub-Cellular (Sub-Unit Vaccines)

  1. When can these be used as vaccines?
  2. Give examples
  3. What is VITAL in ensuring the safety of such vaccines?

  1. if protective immunity is directed against a particular part of an organism
  • Polysaccharide capsules of pneumococci, haemophilus and meningococci;
  • Surface coat of the hepatitis B virus, which is produced by recombinant DNA technology;
  • Fragmented virus or purified surface antigens of influenza virus vaccines.

3. Removal of all live infectious material


Sub-Cellular (Sub-Unit Vaccines)

Give examples of...


  1. Inactivated whole virus
  2. Sub-Unit


  1. Poliovirus, Rabies, inactivated HAV
  2. Influenza, Hepatitis B (HBV), Papillomavirus vaccine (for cervical cancer)


Sub-Cellular (Sub-Unit Vaccines)

Give examples of...


What are the advantages and disadvantages?


  • Selected virus proteins  or peptides used:
  • Completely safe, except for rare adverse reactions.
  • Specific Antibody and T cell reactions can be selected.
  • Can be made using recombinant DNA techniques


  • Tend to be the least effective. 
  • (Relatively) poor antigenicity (especially short peptides)
  • Vaccine delivery (carriers/adjuvants needed) 


Toxoid Vaccines

  1. How are bacterial toxins used?
  2. Give examples of the two toxoids that are among the two most successful and widely used of all vaccines.
    1. What can these be used in combination with?
    2. What does pertussis act as?

  1. inactivated (usually by formaldehyde) so no longer toxic, but still induce protective antibody- called toxoids.
  2. diphtheria and tetanus
    1. with killed Bordetella pertussis, they constitute the triple vaccine, DTP (diphtheria, tetanus, pertussis).
    2. Pertussis acts as an 'adjuvant' as well as a specific vaccine. 


Adjuvants Enhance the Immune Response when Administered with Antigen


  1. The first substances that were used and why
  2. Where are these adjuvants currently used?
  3. Bacterial products that are also used?

  1. aluminum salts - shown to be safe, convenient and effective. Form a repository of antigen within the tissue.
  2. Aluminum adjuvants - currently used in the DTP vaccine, hepatitis B vaccine, some but not all of the Hib vaccines, and vaccines against Lyme disease, anthrax and rabies.
  3. Bordetella pertussis


(Numerous other materials are being considered or tried experimentally for clinical use)