Vaccination Flashcards
What is a vaccine?
A substance that stimulates the immune system, without causing serious harm or side effects
What is the aim of immunisation?
To provoke immunological memory and protect individuals against a particular diseases if encountered
What are some characteristics of the ideal vaccine?
Safe
Easy to administer
Cheap
Single-dose, needle-free
Stable/ Can be stored for longer periods of time
Active against all variants
Life-Long protection
What are the only types of viruses that can be completely eradicated?
human viruses (viruses that are only spread between humans)
What three things can vaccines work to do?
- Prevent entry - vaccine stimulates production of antibodies which bind to virus and stop it harming cells
- Macrophage: engulfs pathogen - Boosting immune response - the antigens in the vaccine stimulate CD4 Helper T cells
B cell: Makes Ig
CD4 t cells: helps - Killing Infected cells - CD8 killer cells detect the foreign antigens
What are the characteristics of immune memory?
The memory cells can multiply much faster and produce a stronger immune response by generating antibodies which have a higher affinity for antigens
What is R0?
The basic reproduction number - the number of cases one case generates on average over the course of their infectious period
What happens if R0 <1?
The infection will die out eventually
What happens if R0>1?
Then the infection will be able to spread in the population
What is the effective number (Rt) and why is it more useful?
It is similar to R0 but does not assume that everyone is susceptible, and therefore takes into account that people may be immune - helpful as then the true severity can be determined
What is herd immunity?
Those people who are immunised against the virus can help protect those who are not as the virus will be less transmissible amongst those protected
What needs to happen in terms of vaccines if R0 is high?
more people need to be immunised for herd immunity to work
What are the four components of a vaccine?
Active ingredient/ antigen
adjuvant (normally alum)
preservatives stabilising factors eg buffers
water (main ingredient)
What are active ingredients?
A very small amount of a harmless form of the bacteria or virus you are immunising against
What is an adjuvant?
Substances used in combination with the specific antigen to elicit a more robust immune response than if the antigen was just used alone
- has no significant risk to health as it’s very small quantities used
How do adjuvants work?
They engage with pattern recognition proteins which induce danger signals that activate DC’s to present antigen to T cells
Adjuvant stimulates the DC
DC uptakes antigen and moves to Lymph node
Upregulates stimulatory signalling and cytokines
What adjuvant is normally found in vaccines?
Alum
What are 2 new platforms for adjuvants?
AS03 – GSK adjuvant in a number of different vaccines e.g.
Shingrix (chicken pox) Mosquirix (malaria)
New experimental TB New experimental COVID
MF59 – In Seqirus influenza vaccine
Mechanism of adjuvant action?
- Adjuvant stimulates DC
- DC take up antigen and moves to secondary lymphoid tissue
- Upregulation of co-stimulatory signalling and cytokines
What forms of antigen can be found in a vaccine? (CRILD)
Inactivate protein e.g., tetanus toxoid
Recombinant protein
Live attenuated pathogen
Dead pathogen
Carbohydrate
What is an Inactivated Toxoid Vaccine?
A chemically inactivated form of toxin
Benefits of inactivated toxoid vaccines?
Cheap, Safe, well characterised, in use for many decades
Mechanism of Inactivated Toxoid Vaccines?
Induces antibody
Antibody blocks the toxin from binding the nerves
What are disadvantages of toxoid vaccines?
Requires good understanding of biology of infection, not all organisms encode toxins
What is an example of recombinant protein vaccines?
Hep B surface antigen (HbSAg)
How do recombinant protein vaccines work?
It is a recombinant protein from pathogen
It induces classic neutralising antibodies
What are the disadvantages of a recombinant protein vaccine?
Expensive, not very immunogenic, has not proved to be answer to all pathogens
Why are recombinant protein vaccines not effective towards all pathogens?
Protein structure is critical
What is a live attenuated pathogen vaccine?
Vaccine where the pathogen has been weakened, but is still able to replicate so it can trigger an immune response, which is almost identical to what happens in a natural infection
What is an example of an live attenuated pathogen vaccine?
LAIV, BCG
What is a live attenuated vaccine?
Pathogens are attenuated by serial passage. This leads to a loss of virulence factors.
What are the advantages and disadvantages of a live attenuated pathogen?
Advantages: Strong immune response is generated, can induce a local immune response in the site where infection might occur
Disadvantages: Since it is a pathogen, it may infect the immunocompromised, can revert to virulence, attenuation may lose key antigens, can be outcompeted by other infections
What is the mechanism for live attenuated vaccines?
Because they replicate in situ they trigger the innate immune response and boost the immune response
What is a dead pathogen vaccine?
Where the pathogen has been chemically killed by formalin, which induces antibody and T cell responses
what is an example of a dead pathogen vaccine?
influenza
What are some disadvantages of a dead pathogen virus?
- 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 is a conjugate vaccine?
Where the polysaccharide coat component is coupled to an immunogenic “carrier” protein
Which enlists CD4 help to boost B cell response to the polysaccharide, as B cell react strongly to the polysaccharides on some bacteria
The polysaccharide is considered a highly immunogenic part
What are advantages and disadvantages of conjugate vaccines?
Advantages:
Improves immunogenicity
highly effective at controlling bacterial infection
Disadvantages:
Cost
carrier protein interference,
very strain specific,
polysaccharide alone is poorly immunogenic
How do conjugate vaccines work?
extra…
- dendritic cell chops up protein part
- B cell recognises bacterial sugar
Conjugate vaccines involve T and B cells true or false?
False - only B cells
Why do we need new vaccines?
- changing demographics
- changing environments
- new diseases emerging
- increasing (antibiotic) resistance
- old diseases we can’t fix
What are some barriers to future vaccine development?
Scientific challenges
Injection safety
Logistics/ Cold chain
Development issues (15 yrs now)
Cost of production
Public expectation of risk-free vaccines
What are traditional vaccine effective at?
Eliciting humoral responses
And are protective against invariant agents
The more diversity, the less protective
What makes it harder to generate vaccines?
Classic immune memory will only recognise one strain
Therefore vaccine antigens need to cover all the variety
What are the types of vaccines made for COVID-19?
protein
inactivated
VLP
love recombinant viral vector
live attenuated
DNA
saRNA
mRNA
What are the phases of a clinical trial?
Pre-clinical
(the the drug is approved for testing in humans)
Phase 1 - safety in humans (20-80 participants)
Phase 2 - mixture of safety and efficacy studies (100-300)
Phase 3 - shown to be safe and effective (1000-3000)
(then the drug is submitted for FDA approval)
FDA review (MHRA in UK) - licensing (The drug has been approved)
Phase 4 - licensed and approved → then goes into large groups of people + more monitoring (1000+)
How are new vaccines introduced into the UK schedule?
- Recommendations for vaccine policy
Joint Committee on Vaccination and Immunisation (JCVI) - Vaccine policy decisions
Department of Health (DH) - Licensing of vaccine
Medicines and Healthcare products Regulatory Agency (MHRA) - Purchase of vaccine
Department of Health from pharmaceutical companies - Control of vaccine (including batch release)
National Institute for Biological Standards and Control (NIBSC) - Post licensure assessment and changes
PHE/ JCVI (Epidemiology, assessment, trials)
What needs to be considered for the scheduling of the vaccine?
Aim
Need
Scheduling with other vaccines
Availability
Cost
Population accessibility
Cultural attitudes and practices
Facilities available for delivery
Give an example of a high variable virus?
HIV
