7. Vaccination

Question 1

Describe the history of vaccinations:

Answer 1

• 1796: Smallpox vaccine developed- exposure of subject to cowpox made them resistant to smallpox
• 1955: injectable polio vaccine introduced
• 1962: oral polio vaccine introduced
• 1967: smallpox eradication program started
• 1979: smallpox eradicated from world
• 2016: eradicated of polio in sight

Question 2

What are the outcomes of vaccination?

Answer 2

1. Prevention of disease (symptoms)
2. Prevention of transmission
3. Eradication of disease
4. Potentially- treatment of existing disease e.g. cancer, alzhiemers

Question 3

How was small pox eradicated?

- Why was it successful?

Answer 3

• Smallpox was eradicated by vaccination- vaccine = cow pox virus that protects against smallpox
• Eradication program began in 1967 and declared in 1980 (based on vaccination and quarantine)

Why was vaccination successful in eradicating small pox?

• disease is limited to humans
• no long term carriers
• disease is always recognizable
• few serotypes/variants (unlike influenza virus)
• stable, cheap and effective vaccine available
• eradication is cost effective
• there is global surveillance

Question 4

Based on the success of smallpox eradication what other diseases have the potential to be successfully eradicated by vaccine?

Answer 4

• Polio
• Rubella
• Measles
• Typhoid
• Hep B

Question 5

What is the polio virus?

Answer 5

• Highly infectious viral disease spread by fecal oral route
• Mostly infects children <5
• Multiplies in intestine and invades nervous system
• Can cause paralysis in hours and has a 5-10% mortality rate
• There are 3 main strains of polio virus

Question 6

What are the two types of polio vaccine?

Answer 6

1. Inactivated (Salk) Vaccine - 1955:
   - 3 strains of virus grown in cell line and then treated with formalin so they are inactivated (killed)
   - injected
2. Attenuated oral vaccine OPV (Sabin)- 1962:
   - 3 strains of virus grown in cell line and then passaged until they developed mutations to make them less virulent (attenuated)
   - orally administered
   - in immuno-comprimised people can cause actual polio infection

Question 7

What does vaccination achieve in individuals and society?

Answer 7

Individual: protection of the individual against disease

Society: protection of a population against disease

Question 8

What is herd immunity?

Answer 8

• Is a form of indirect protection from infectious disease that occurs when a large percentage of a population has become immune to an infection (via vaccination), thereby providing a measure of protection for individuals who are not immune
• Coverage rates do not need to be 100%
• Vaccinations thus help provide community based disease control
• Insufficient coverage can lead to outbreaks and persistence of disease

Question 9

What are the two types of immunisation?

Answer 9

1. Passive:
   - transfer of immunity to protect patient using specific antibodies
   - rapid onset of protection (good for outbreaks when exposure is suspected)
   - best given before infection
   - limited duration
   e. g. antitoxins (snake bite), tetanus, Hep A, measles
2. Active:
   - Induction of a specific protective immune response by exposure to antigen
   - Aim is to introduce the immune system to a safe form of a micro-organism that will induce an immune response
   - Provides a protective secondary immune response if infection occurs

Question 10

What are the requirements of a an ideal vaccination?

Answer 10

1. Safe (minimal, acceptable side effects)
2. Produce a protective immune response
3. Long lasting response
4. Stable (dont require cold-chain)
5. Single dose
6. Oral/inhaled administration
7. Low cost

Question 11

What must vaccines contain?

Answer 11

• At least one component of the microorganism which is it attempting to protect against
• The greater the number of components- the more the immune response will resemble that against the target organism

Question 12

What are some features of killed/inactivated vaccines?

Answer 12

• Very safe
• Heat stable
• Parenteral (injected)
• Multiple doses
• Adjuvant required a (substance which enhances the body’s immune response to vaccine)
• High cost
• Can have a short or long duration of immunity
• Immunity mainly IgG

e. g. polio vaccine (Salk)
e. g. Influenza vaccine
e. g. Hep A vaccine
e. g. Typhoid vaccine
e. g. Cholera vaccine

Question 13

What are some features of live/attenuated vaccines?

Answer 13

• Orally administered
• Single dose
• No adjuvant
• Low cost
• More immunogenic
• Long duration of immunity
• immunity can spread through population
• possible reverse to virulence
• requires cold chain
• IgG, IgA and cell mediated immunity

e. g. BCG- tuberculosis vaccine
e. g. OPV (Sabin)- oral polio virus
e. g. most vaccines including- MMR vaccine, chickenpox (varicella) vaccine, Rubella vaccine, YF vaccine

Question 14

What are the 4 main types of vaccines?

Answer 14

1. Live attenuated
2. Killed/inactivated
3. Subunit vaccines
4. New novel vaccines
   e. g. recombinant antigen vaccines

Question 15

What are subunit vaccines?

Answer 15

• Used when immunity depends on antibodies to only a particular microbial component that can be purified, can be:
• a protein e.g. Toxoid
• a polysaccharide e.g. polysaccharide capsules such as Neisseria meningitidis vaccine
• a non-infectious viral like particle such as HPV vaccine

Question 16

What are toxoids?

Answer 16

• A type of sub-unit vaccine that contains inactivated bacterial toxins that generate an immune response (antibodies) against the toxin
  e. g. DTaP vaccine (diptheria, pertussis and tetanu)

Question 17

What are recombinant antigen vaccines?

Answer 17

• When the protective antigen (the antigen then when exposure occurs creates immunity) is known it can be produced by recombinant DNA technology
• Useful in cases where the causative agent is difficult to grow
• Can clone the relevant genes into a vector such as E coli or yeast

e. g. HPV virus- empty-viral like particles (VLP)
e. g. Rabies- G- antigen
e. g. Influenza- recombinant hemagglutinin
e. g. M. tuberculosis- 6 immunogenic proteins fused (in mouse trials)

Question 18

What are adjuvants?

Answer 18

• Adjuvants are substances that enhance the immune response by:
  1. Increasing local inflammation
  2. Depot effect for slow, sustained release of antigen
• Used in vaccines containing soluble vaccines that are less immunogenic tha particulate antigens e.g. single protein/toxoid vaccine

Common adjuvants:

• Insoluble aluminium salts
• oil/water emulsions (not in humans)
• protein carriers for polysaccharide vaccines
• toll receptors e.g. LPS, cytokines

Question 19

What are 5 new fields of vaccine development?

Answer 19

1. Insertion of foreign genes in live vectors: multivalent vaccines
2. DNA vaccination
3. Edible vaccines
4. Shape mimic vaccines
5. Nanopatches

Question 20

How does the insertion of foreign genes into live vectors work in vaccine development?

Answer 20

• New approach
• Multivalent attenuated viral vectors and bacterial vectors
• Involves inserting foreign target pathogen DNA into the genome of a viral or bacterial vector
• This vector transports the target pathogen DNA into the body and creates an immune response
  e. g. orally administered attenuated salmonella typhii used as vector for Strep pneumoniae surface protein antigen
  e. g. attenuated canary pox virus used as vector for 3 HIV proteins

Question 21

How does DNA vaccination work?

Answer 21

• Injection of naked DNA comprising a foreign (target microbe) gene and a plasmid
• Foreign gene under control of eukaryotic promoter (so it is transcribed in human cells)
• Still not used in humans

Question 22

How do edible vaccines work?

Answer 22

• Involve genetically engineering plants/animals e.g. potatoes so they produce agents that will express vaccine antigens

Question 23

How do shape mimic vaccines work?

Answer 23

• These vaccines mimic the shape of antigens (as antibodies bind by recognising the 3D shape) rather than mimicing DNA sequence of antigen
• Include:
• Anti-idiotypes: antibody molecules thare are copies of the antigen shape
• Mimotypes: a synthetic peptide that mimics structure of epitope

Question 24

What are nanopatches?

Answer 24

• A mode of needle free vaccination
• A small stamp sized piece of metal covered in thousands of microscopic projections dry coated in antigen
• Requires 100x lower dose
• No adjuvents, refrigeration or preservatives needed
• Very cheap

Question 25

Why do vaccines sometimes fail?

Answer 25

- Wrong sort of immune response - Response too low - Reposes are induced to the wrong target - Non-responders in the population - Immature immune system - Immunosuppression - Immune evasion (diversity and antigenic variation by microbe)

Question 26

What are some complications and side effects of vaccination?

Answer 26

- Infectious material in vaccine (incomplete inactivation - Allergic responses to vaccines - Adverse reactions (e.g. seizures post DTP vaccination- fixed by making DTaP vaccine- has acellular pertussis) - Vaccine toxicity - Harmful effects upon foetus - Harmful effects in immunocomprimised host of live vaccines (hence move from OPV to IPV)