Scientific basis of vaccines Flashcards
What is smallpox caused by?
Caused by Variola
What are the scientific principles from jenners experiment?
- Challenge dose-proves protection from infection
- Concept of attenuation
- Concept that prior exposure to agent boosts protective response
- Cross specific protection-antigenic similarity
What is the eradication of smallpox due to?
- Vaccination programmes
- Case finding(Surveillance)
- Movement control
Why was eradication of smallpox possible?
- No subclinical infection
- After recovery, the virus was eliminated
- No animal reservoir
- Effective vaccine
- Slow spread, poor transmission
What is a vaccine?
Material from an organism that will actively enhance adaptive immunity
What does a vaccine increase the ability of?
Increases the ability of the active immune response to recognise antigens and generate the correct type of immune response that will lead to immunoprotection, not just recognition
What does a vaccine produce and what does this allow and drive?
• Produces an immunologically primed state that allows for rapid secondary immune response on exposure to antigen
Driving T cell memory
What does a vaccine prevent and not prevent?
Prevention of disease but not infection
What does a vaccine require?
Requires immunological memory
Vaccination rationale
- Protection of individual reduces rate and severity of diseases
- Protection of the population results in herd immunity
- Can lead to eradication of disease
- Need a balance between vaccine uptake rate and reservoirs of infection
Once vaccinated, what is natual boosting?
having immune response boosted as a result of exposure to infectious agent in community
What are the 2 types of immunity?
- Active immunity
- Innate immunity
What are the 2 types of immunity?
- Active immunity
- passive immunity
What is the immune response to antigen during primary exposure?
○ 5-7 days –> antibody response
○ 2 weeks for a full response
○ IgM to IgG switching
○ Memory B and T cells
What is the immune response to antigen upon secondary exposure?
2 days for full protective responses
What are the general principles of a vaccine?
- Induce correct type of response
- Induce response in right place
- Duration of protection
- Age of vaccination
Why are antibodies sufficient for infection that exists in gut or bloodstream?
For infections that exist in the gut or bloodstream, antibodies will be sufficient because they will bind to the viruses and neutralise them
Why does a systemic infection need more than just antibodies?
A systemic infection (that lives inside cells) will need more than just antibodies as they cannot get inside the cells so need T cell immunity
What antibody is present in baby milk and how long does it last for?
IgA in milk – lasts for 6 months
What are the natures of antigens?
- Monotypic
2. Polytypic
Variability of monotypic antigens
Not variable
Diversity of polytypic antigens and examples
○ Undergo massive antigenic diversity
i.e. flu, gonorrhoea
Why are most antigens immunogenic but not immuno-protective?
Most antigens are immunogenic but NOT immuno-protective as they cannot predict which antigens will be produced next
What are the 3 types of vaccines?
- Live attenuated organism
- Killed, whole organism
- Sub-unit vaccines(Individual components)
What do live attenuated organism vaccines not cause and why?
○ Does not cause infection because it has been attenuated
What do live attenuated organism vaccines not cause and why?
○ Does not cause infection because it has been attenuated
What do live attenuated organism vaccines give against the disease?
○ Does give T cell immunity against disease
How many mutations does polio type 1 have?
Polio (Sabin) type I has 57 mutations
Why is boosting not required if a patient is given a live viral vaccine?
If you give live viral vaccine, viral vaccine does not need boosting as it lives in the body for long enough to induce protective immunity
What do killed, whole organisms vaccines need in order to get the correct type of immune response?
In order to get the correct type of immune response, you need boosters to raise the levels
What is reactogenicity?
property of a vaccine of being able to produce common, “expected” adverse side effects
What components have been identified of the organism that gives good protective immunity in subunit vaccines?
§ Proteins
§ Toxoids (diphtheria; tetanus)
§ Peptides (synthetic)
§ Polysaccharide - poor antigens
Why is it difficult to make vaccines from polysaccharides?
Difficult to make vaccines from polysaccharides because they give poor immune response to children under the age of 2 as they don’t recognize polysaccharides very well
How do you make a conjugated vaccine with a polysaccharide?
□ Need to conjugate polysaccharide to a protein – use an outer membrane protein and inactivated toxin to make conjugated vaccine (e.g. MenC; Hib;)
What are recombinant proteins and what are made from them?
proteins that are cloned into bacteria/yeasts and made into large amount of proteins and then put into vaccines
Make subunit vaccines
What do subcellular fractions use as part of the subunit vaccine?
§ Use surface blebs of membrane as part of the vaccine
What do toxins usually cause?
• Toxins usually cause direct tissue damage and disease
How do you get a toxoid from a toxin?
• If you purify the toxin and inactivate with formaldehyde you get toxoid
What can toxoids be used as and what can they induce?
These can induce antibody responses that neutralise toxins if you get infected with the organism
Why are bacterias capsular polysaccharides as vaccines less immunogenic in children <2yrs?
○ Short term memory
○ No T cell immunity
How can you enhance immunogenicity in children <2yrs old for bacterial capsular polysaccharides as vaccines?
• Enhance immunogenicity by protein conjugation
○ Toxoids D/T + outer membrane proteins
○ Long lasting immunity and response in children
What does conjugation link?
- Conjugation links polysaccharide antigen to protein carrier (e.g. diphtheria or tetanus) that the infant’s immune system already recognises in order to provoke an immune response
- Link membrane to carrier protein
How do conjugates work?
- If polysaccharide is linked to protein, the B cell recognises the protein and presents the protein to a T cell
- T cell recruits cytokines that encode the polysaccharide specific B cell to make more potent antibody at higher levels
- Does this because the carrier protein recruits Th cells and cytokines that activate the B cells
What are adjuvants?
Adjuvants are chemicals/lipid structures that enhance the immune response using the vaccine components
What do vaccine adjuvants enhance?
• Enhance immune response to antigen
What do vaccine adjuvants promote?
• Promote uptake and antigen presentation
What do vaccine adjuvants stimulate?
• Stimulate correct cytokine profiles
What do vaccine adjuvants allow antigens to do and in order to boost what?
• They allow antigen to stay in bloodstream longer to boost immune response
