Vaccination Flashcards
The effects of adjuvants on the immune response
• To increase the immunogenicity of weak antigens
• To enhance speed and duration of immune response
• To stimulate and modulate humoral responses, including antibody isotype
• To stimulate cell-mediated immunity
• To improve induction of mucosal immunity
• Enhance immune responses in immunologically immature patients, particularly infants
To decrease the dose of antigen required; reducing costs and eliminating inconvenient requirements for booster shots
What is the ultimate aim of the adjuvants
Activate the immune system to respond more rapidly to infection and for the adaptive immune response to be more specific
Examples of adjuvants
Aluminium based mineral salts (alum), MF59, Monkphosphoryl lipid A ( MPL), virosomes
What is a vaccine
Something that stimulates the immune system without causing harm or serious side effects - provokes immunological memory
Ideal vaccine
Completely safe
Easy to administer
Single dose, needle-free
Cheap - many people need to be vaccinated across the world.
Stable - logistics for storage and transport.
Active against all variants
Life-long protection
Process of the immune response in regard to a vaccine
Pathogen -> innate immune response, recognised as foreign. Innate effectors e.g. Macrophages, NK cells, neutrophils killing non specifically. -> antigens taken up by dendritic cells; become APCs -> communicate with t-cells. -> clonal selection and expansion. -> after it passes, development of immune memory.
Difference in response between the first and second encounters of the immune response
- On first encounter (primary response), takes days to develop
- On repeat infections (secondary response), is faster and stronger
Different forms of antigen
Inactivated protein Recombinant protein Live attenuated pathogen Dead pathogen Carbohydrate
Inactivated protein
Tetanus toxoid
Recombinant protein
Hep B
Live attenuated pathogen
Polio / BCG
Dead pathogen
Split flu vaccine
Carbohydrate
S.pneumonia
What is in a vaccine
Antigen ( in one of the forms)
adjuvant , normally alum , sometimes proprietary
Stabilising stuff (e.g. Buffers-PBS)
Water
How do vaccines stop infection
1) stop entry of pathogen - antibodies
2) enable killing of infected cells / engulfment by - macrophage and CD8
3) boost immune response on subsequent exposure - CD4 and B cells which make Ig
Concept of herd immunity
In diseases that can be passed from person to person, it is more difficult to pass that disease easily when there are those who are immune to it. 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
Mechanism of inactivated toxoid vaccines ( eg. Tetanus toxoid) and advantages and disadvantages
- Description: Chemically inactivated form of toxin
- Mechanism: Induces antibody, antibody blocks the toxin from binding the nerves
- Advantages: Cheap, well characterised, safe, in use for many decades
- Disadvantages: Requires good understanding of biology of infection, not all organisms encode toxins, tiny risk of failure to inactivate/ impurities
Recombinant protein vaccines
- Example: Hep B Surface Antigen (HbSAg)
- Description: recombinant protein from pathogen
- Mechanism: Induces classic neutralising antibodies
- Advantages: Pure, safe, because low strain variation and human only host highly protective
- Disadvantages: Relatively expensive, has not proved to be answer to all pathogens (see below)
Possible problem with recombinant protein vaccines
The issue is sometimes when proteins are synthesised, they may fold differently which means the vaccine would be ineffective.
Why polysaccharide vaccines
Some pathogens don’t have antigens on the surface so we use polysaccharide vaccines.
Polysaccharide vaccines have a history of safety and efficacy in preventing
meningococcal disease.
How do polysaccharide vaccines work
use purified polysaccharides from specific Neisseria meningitidis serogroups as antigens to produce serum antibodies that activate complement-mediated bacteriolysis and phagocytosis.
Advantages of polysaccharide vaccines
You can have buvalent and tetravalent vaccine ( can work against two different antigens)
They also have a high degree of safety and good short term efficacy in older children and adults
Bacterial coat vaccine
- Bacterial often have a capsule
- This is made of polysaccharide
- Which is not very good at inducing a B cell response (it is a T independent antigen)
- Alternative approaches are needed
Conjugate vaccines
- Example: S. pneumoniae
- Description: Polysaccharide coat component is coupled to an immunogenic “carrier” protein
- Mechanism: Protein enlists CD4 help to boost B cell response to the polysaccharide
Advantages of conjugate vaccine
Improves immunogenicity, highly effective at controlling bacterial infection
Disadvantages of conjugate vaccine
- Cost
- carrier protein interference,
- very strain specific,
- polysaccharide alone is poorly immunogenic
Dead pathogen vaccines
• Example: Influenza split vaccine
• Description: Rather than using a component of the pathogen , it can be chemically killed
Mechanism ; induced antibody and Tcell responses
Advantages of dead pathogen viruses
Leaves antigenic components intact and in context of other antigen. Immunogenic because of the inclusion of other components
Disadvantages of dead pathogen viruses
- 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)
Live attenuated vaccines
- Example: BCG, LAIV, OPV
- Description: Bugs are attenuated by serial passage. This leads to a loss of virulence factors
- Mechanism: Because they replicate in situ they trigger the innate response and boost the immune response
Advantages of live attenuated vaccines
Induce a strong immune response. Can induce a local immune response in the site where infection might occur (e.g. LAIV)
Disadvantages of live attenuated vaccines
- Can revert to virulence
- Can infect immunocompromised (BCG/ HIV)
- Attenuation may lose key antigens
- Can be competed out by other infections
Adjuvant definition
Substances used in combination with a specific antigen that produced a more robust immune response than the antigen alone.
How does an adjuvant work
- Adjuvant stimulates the DC
- DC uptakes antigen and moves to Lymph node
- Upregulates stimulatory signalling and cytokines
- Adjuvants engage with pattern recognition receptors (PRR)
- They induce ‘danger signals’ that activate dendritic cells to present antigen to T cells
- Also the trigger to license the response
Why do we need new vaccines
Changing/ aging demograohcs
Changing environment ( dengue and other arboviruses)
New disease like COVID
Old diseases we can’t fix like HIV/Tb /Malaria
Antibiotic resistance (MrSA , all bacteria)
