Scientific Basis of Vaccines Flashcards
What are the 4 principles from Jennerβs experiments?
1) challenge dose - proves protection from infection
2) Concept of attenuation
3) Concept that prior exposure to agents boosts protective response
4) cross species protection - antigenic similarity
What were the three things that contributed to smallpox eradication?
β They had vaccination programmes
β Case finding (surveillance)
β movement control
What were the 5 things that made the eradication of smallpox possible?
1) No subclinical infecitons (no asymptomatic spreaders)
2) after recovery the virus was eliminated - no carrier states
3) No animal reservoir
4) effective vaccines
5) slow spread and poor transmission
What is the definition of a vaccine?
β material from an organism that will :
β actively enhance adaptive immunity
β produces an immunologically primed state that allows for rapid secondary immune response on exposure to the antigen
β prevent disease but not infection
What are the 4 complications in measles?
β 1 in 15 pneumonia
β otitis media
β bronchitis
β 1 in 5000 encephalitis
What are the 2 complications of the measles vaccine?
β 1 in 1000 fever/convulsions
β 1 in 400,000 meningo-encephalitis
What is one complication of diphtheria?
β 5% mortality
What is one complication of the diphtheria vaccine?
β occasional swelling
What are the 2 complications of whooping cough?
β 0.1% mortality
β frequent pneumonia, encephalopathy
What is one complication of the whooping cough vaccine?
β 1 in 600,000 encephalopathy
How can active immunity be induced?
β Natural exposure
β Infection
β Vaccination
What is the duration of active immunity?
β long term
How does passive immunity occur?
β prophylaxis / treatment
What is the duration of passive immunity?
β short term
Give three examples of passive immunity?
β anti-tetanus serum from horses in WW1 decreased mortality by 30x
β post-exposure protection in rabies + vaccine
βpooled human immune serum with high amounts of antibodies to protect babies from VZV
How long does it take for an antibody response during primary exposure?
β 5-7 days
How long does it take for a full response during primary exposure?
β 2 weeks
What class switching occurs in antibodies during a primary exposure?
β IgM β IgG
How long does a full response take during secondary exposure?
β 2 days
What components are used to make a vaccine from a bacteria or a virus and why?
β usually surface proteins
β if you use a protein from inside the bacteria or virus, the body never comes into contact with the protein because it is internal
What are good targets for vaccines?
β Surface proteins
β polysaccharides
β toxins
What are 4 important considerations when vaccinating?
1) inducing the correct type of response
2) Inducing the response in the right place
3) duration of protection
4) age of vaccination
What kinds of responses are induced with polio and TB?
β Polio : antibodies
β TB : cell mediated immunity
Where should the immune response be with flu, polio and yellow fever?
β flu, polio : mucosal
β yellow fever : systemic
Why do you need a mucosal response with the flu and polio?
β Flu affects the respiratory system
β polio affects the gut
Which one of paraenteral and oral vaccines provide the best mucosal immunity?
β oral vaccines because they are processed by MALT (mucosal associated lymphoid tissue) and have good IgA
What are short term vaccines and why do you need them?
β during travel
β only antibodies
Why do you need booster vaccines?
β natural immunity decreases
β seasonal epidemics
What disease has a long incubation time?
β measles
Which disease has a short incubation time?
β cholera
Where is it difficult to induce long-lasting immunity?
β at mucosal surfaces
What antibodies are in breast milk and how long do they last?
β IgA
β 6 months
Why are maternal antibodies in neonates a problem with live attenuated vaccines?
β the virus is neutralised by the maternal antibody
What are 5 examples of live attenuated vaccines?
β BCG β polio β MMR β yellow fever β VZV
What is a monotypic infection?
β measles is not very different across the types of measles (low antigenic variability) so you only get it once
What is a polytypic infection?
β flu and gonorrhoea (high antigenic variability) so you can get it multiple times
What are most antigens?
β immunogenic but not immunoprotective
How many mutations does polio have?
β 57
What are 5 examples of killed whole organism vaccines?
β pertussis β flu β polio β cholera β hep A
Why does a live vaccine not need boosting?
β the live vaccine survives long enough to induce good protective immunity
β virus keeps multiplying so the immune response is greater
What do subunit vaccines use?
β Proteins β Toxoids β Peptides β polysaccharides β recombinant β sub-cellular fractions β surface antigens β virulence determinant
What modifications do polysaccharide vaccines have to undergo and why?
β Conjugated to a toxoid + outer membrane protein
β because children under the age of two donβt recognise polysaccharides
What are recombinant vaccines?
β proteins that are injected into yeast or bacteria to replicate
Which vaccines use surface antigens?
β Hepatitis B
β influenza haemagglutinin
β meningitis B
What is a virulence determinant example?
β aP pertussis β adhesion + toxoid + OMMP
How are toxoids formed?
β toxins inactivated with formaldehyde
What 3 diseases are toxin mediated?
β Diphtheria
β whooping cough
β tetanus
What do toxoid vaccines induce?
β antibody responses that neutralise toxins
Why are bacterial capsular polysaccharides not used?
β poor antigens and short term memory
β no T cell immunity
β less immunogenic in children less than 2 years old
β poor IgG2 responses
What is the function of IgG2?
β IgG2 promotes opsonisation and major recognition of polysaccharides
How do you enhance the immunogenicity of bacterial capsular polysaccharides?
β protein conjugation
What do toxoids + outer membrane proteins lead to?
β long lasting immunity and response in children
What is the MenC vaccine?
β Neisseia Meningitidis group C
What is the Hib vaccine?
β Haemophilus influenzae type B
What does conjugation do?
β links polysaccharide antigen to protein carrier that the infantβs immune system already recognises in order to provoke an immune response
What happens if you only use a polysaccharide in a vaccine?
β poor recognition and no T cell help
What happens if you link a polysaccharide to a protein in a vaccine?
β The B cell recognises the protein
β it presents the protein to a T cell that recruits cytokines to help the B cell make much more specific and potent antibodies
What are vaccine adjuvants?
β Chemical or lipid structures that enhance the immune response using the vaccine components
What are the 3 functions of vaccine adjuvants?
β enhance the immune response to antigens
β promote uptake and antigen presentation
β stimulate correct cytokine profiles
What is an example of a vaccine adjuvant?
β aluminium salts
What are the 3 functions of aluminium salts?
β Form trapped particles
β slow release of antigen
β large number of Mps exposed
What are the advantages of live attenuated vaccines?
β long lived immunity
β good immune response
What are the disadvantages of live attenuated vaccines?
β requires cold chain β insufficient attenuation β reversion β immunosuppressed β foetal damage
What are the advantages of whole killed organisms?
β short or long
β IgG
β poor CMI
β stable
What are the disadvantages of whole killed organisms?
β inactivation and immunogenicity
β contamination
β toxicity/allergy
β autoimmunity
