Lecture 20: Vaccination Flashcards
What is a vaccine?
Something that stimulates the immune system, without causing serious harm or side effects
What is the aim of immunisation?
To provoke immunological memory to protect individual against a particular disease if you later encounter it
What makes a vaccine ideal?
- safe
- easy to administer
- single dose, needle-free
- cheap
- stable
- active against all variants
- life-long protection
What is significant about immune memory?
Movement to peak immune system response is much faster and stronger in second encounter of particular pathogen
Outline the principles of vaccination.
- expose immune system/naïve immune cells to antigen
- primary expansion of effector cells (clonal expansion)
- contraction (no. effector cells decreases, put into memory)
- second encounter = secondary expansion of effector cells (much faster and stronger)
How do vaccines stop infection?
1) Stops virus or bacteria getting into host cells - antibodies block entry, macrophage engulfs pathogen
2) Enables killing of infected cells - CD8+ killer T cells, T cells clear infected cells
3) Boosts immune responses - boosting CD4+ helper cells
How does clonal expansion of B cells lead to a highly specific antibody for the foreign antigen?
The B cell already made by our body that produces antibodies that best recognise the foreign antigen is the B cell that is selected to expand i.e. the better B cells survive (affinity maturation)
What is R0?
Basic reproduction number - no. cases one case generates on average over course of infectious period
What does it mean if R0 <1?
Infection will die out in long run
What does it mean if R0 >1?
Infection will be able to spread in a population
What will an effective vaccine do to R0?
Bring R0 to below 1
What is the principle behind herd immunity?
The more immune individuals there are, the less likely it is that a susceptible person will come into contact with someone who has the disease
What’s in a vaccine?
- antigen (could be in one of a variety of forms)
- adjuvant (normally alum), sometimes something proprietary
- stabilising stuff (e.g. buffers - PBS)
- water
What forms could antigen be in within a vaccine?
- inactivated protein e.g. tetanus toxoid
- recombinant protein e.g. Hep B
- Live attenuated pathogen e.g. Polio, BCG
- Dead pathogen e.g. Split flu vaccine
- Carbohydrate e.g. S. pneumoniae
What are inactivated toxoid vaccines?
Chemically inactivated form of toxin
What is the mechanism of action of inactivated toxoid vaccines?
Induces antibody, antibody blocks toxin from binding the nerves
Formulin locks shape, makes it inactive
What are the advantages of inactivated toxoid vaccines?
Cheap, well characterised, safe, in use for many decades
What are the disadvantages of inactivated toxoid vaccines?
Requires good understanding of biology of infection, not all organisms encode toxins, tiny risk of failure to inactivate/impurities
What are recombinant protein vaccines?
Uses recombinant protein from pathogen - gene of one organism moved to another, looks same as pathogen
What is the mechanism of action of recombinant protein vaccines?
Induces classic neutralising antibodies
What are the advantages of recombinant protein vaccines?
Pure, safe, because low strain variation and human only host highly protective
What are the disadvantages of recombinant protein vaccines?
Relatively expensive, has not proved to be answer to all pathogens
What are conjugate vaccines?
Polysaccharide coat component is coupled to an immunogenic “carrier” protein
What is the mechanism of action of conjugate vaccines?
Protein enlists CD4 help to boost B cell response to polysaccharide
What are the advantages of conjugate vaccines?
Improves immunogenicity, highly effective at controlling bacterial infection
What are the disadvantages of conjugate vaccines?
Cost
carrier protein interference,
very strain specific,
polysaccharide alone is poorly immunogenic
What are dead pathogen vaccines?
Rather than using a component of the pathogen, it can be chemically killed.
What is the mechanism of action of dead pathogen vaccines?
induces antibody and T cell responses
What are the advantages of dead pathogen vaccines?
Leaves antigenic components intact and in context of other antigen. Immunogenic because of the inclusion of other components.
What are the disadvantages of dead pathogen vaccines?
Fixing/ killing can alter chemical structure of antigen.
Quite “dirty”.
Requires the capacity to grow the pathogen (H5N1).
Vaccine induced pathogenicity a risk.
Risk of contamination with live pathogen (Polio)
What are live attenuated vaccines?
Bugs are attenuated by serial passage. Leads to loss of virulence factors.
What is the mechanism of live attenuated vaccines?
Because they replicate in situ they trigger the innate response and boost the immune response.
What do adjuvants do?
- engage w/pattern recognition receptors (PRR)
- induce ‘danger signals’ that activate dendritic cells to present antigen to T cells
- all trigger to license the response
- used w/specific antigen to induce more robust response
How do adjuvants license DCs?
- adjuvant stimulates DC
- DC uptakes antigen and moves to lymph node
- upregulates stimulatory signalling and cytokines
What vaccines are given at 8 weeks old?
- Diphtheria, tetanus, Pertussis (whooping cough), polio, Haemophilus influenzae type B (HiB) and hepatitis B (6-in-1 vaccine)
- Pneumococcal conjugate vaccine (PCV)
- MenB
- Rotavirus
What vaccines are given at 12 weeks old?
- Diphtheria, tetanus, pertussis, polio, Hib and hepatitis B
- Rotavirus
What vaccines are given at 16 weeks old?
- Diphtheria, tetanus, pertussis, polio, Hib and hepatitis B
- Pneumococcal
- MenB
What vaccines are given to 1 year olds?
- HiB and MenC
- Pneumococcal
- MMR
- MenB booster
What may eligible paediatric age groups be given?
Live attenuated Influenza vaccine (each year from September)
What vaccines are given at 3 years 4 months old?
- Diphtheria, tetanus, pertussis and polio
- MMR
What vaccines are given to girls and boys aged 12 to 13 years?
- HPV (2 doses 6-24 months apart)
What vaccines are given to 14 year olds (year 9)?
- Tetanus, diphtheria and polio
- MenACWY
What vaccines are given to people 65 years and over?
- Pneumococcal
- Influenza
- Shingles