Scientific Basis of Vaccines Flashcards
What is variolation?
Variolation (with variola minor) and Vaccination (vaccinia) - taking scabs from mild disease and inoculating people
What are the scientific principles learnt about vaccines from Jenner’s experiments?
- Challenge dose – proves protection from infection
- Concept of attenuation
- Concept that prior exposure to agent boosts protective response
- Cross-species protection – antigenic similarity
How was smallpox eradicated?
- Vaccination programmes
- case finding (surveillance)
- and movement control
Why was smallpox eradication possible?
- No subclinical infections (mild / full blown)
- After recovery, the virus was eliminated - no carrier states
- No animal reservoir
- Effective vaccine (live vaccinia virus)
- Slow spread, poor transmission
What is a vaccine?
Material from an organism that will actively enhance adaptive immunity
How do vaccines provide immunity?
Produces an immunologically “primed” state that allows for a rapid secondary immune response on exposure to antigen - drives T cell memory
What is the role of vaccines?
Prevention of DISEASE not infection
- can’t stop people getting infected but can stop disease symptoms occurring
How do we achieve long lasting immunity with vaccines?
Long lasting - requires immunological memory
Antibodies and/or T cells (humoral and cell mediated immunity)
What are the aims of vaccines?
- Protection of the individual: ↓rate/severity
- Protection of the population: Herd Immunity
- Eradication of disease
What factors determine eradication of a disease?
Eradication requires balance between the epidemic risk to individuals and a population
What is the am of the rubella vaccine?
Rubella: a mild disease. Aim is to prevent congenital damage, not protect population
How is immunity memory maintained?
Herd Immunity memory boosted by periodic outbreaks of disease in community and vaccines
Why are booster vaccines required?
As disease rates decline - no natural boosting
Increases importance of vaccination uptake rates
Outline the risks and benefits of vaccination against measles
Infection Complications
- 1/15 pneumonia, otitis media, bronchitis
- 1/5000 encephalitis (15% mortality)
Vaccination Damage
- 1/1000 fever/convulsions
- 1/400,000 meningo encephalitis
What are the risks and benefits of vaccinating against diphtheria?
Infection Complications
- 5% mortality
Vaccination Damage
- Occasional swelling
Outline the risks and benefits of the whooping cough vaccination
Infection Complications
- 0.1% mortality
- frequent pneumonia
Vaccination Damage
- 1 / 600,000 encephalopathy
What are the different types of active immunity?
- Innate / Adaptive (Cell Mediated Immunity; antibodies)
- Natural exposure (carriage)
- Infection
- Vaccination
Long effect
What are the different types of passive immunity?
Antibody from another source: serum
- Prophylaxis and/or treatment
Short effect
Describe the primary immune response to antigens
Primary exposure 5-7 days → antibody response
2 weeks for a full response
- IgM to IgG switching
- memory B and T cells
How long does a secondary immune response last?
Secondary response 2 days for full protective response (prior exposure)
How do we remain protected against pathogens after exposure?
Post-exposure immunoprotection due to response vs specific antigens
e. g. surface proteins, polysaccharides, toxins
- good targets for vaccine candidates
What are the general principles of vaccines?
- Induce correct TYPE of response
- antibodies / cell mediated - Induce response in RIGHT PLACE
- mucosal sIgA / systemic - Duration of protection
- Age of vaccination
Why are antibody vaccines insufficient for systemic infections?
Antibodies aren’t sufficient for systemic infections as they can’t enter host cells or viruses
What are the different durations of vaccines?
Short-term (travel) antibody sufficient
Long-term memory essential
Boosters - natural (seasonal epidemics; carriage)
- vaccines
How does the type of infection effect the duration of the vaccine?
long incubation time (systemic) - measles
short incubation time (surface) - cholera
How are neonates protected against infection?
Maternal antibodies present in neonates for protection
sIgA in milk lasts for ~ 6 months
Why are maternal antibody presence in neonates a problem for some vaccines?
Problem for live attenuated vaccines e.g. MMR
Virus neutralised by maternal antibody → no protection ∴ need to wait until maternal ab cleared before administering live attenuated vaccines in babies
When should young babies first be vaccinated with live attenuated vaccines?
Vaccinate > 9 months
But many babies are infected by then in endemic areas
What are the different natures of antigens?
Monotypic (measles) - get once
Polytypic (flu, gonorrhoea) - multiple
What factors make vaccine production difficult?
Antigen variation + Genetic diversity makes it difficult to produce vaccinations
How do antigens effect the immune system?
Most antigens are immunogenic but NOT immuno-protective
Unless their surface components can neutralise the effect of the organism by preventing adherance or neutralizing its toxins
What is a live attenuated vaccine?
One or more components of a microorganism
e.g. BCG, polio(Sabin), MMR, yellow fever, VZV
How is a live attenuated vaccine produced?
- serial passage,
- low temperature adaptation,
- recombinant genetics
( S.typhi Ty21a; galE + aroA/B/C mutant) - selection of natural attenuated strains
Why are booster injections given?
3 separate doses to overcome strain antagonism and ensure adequate immune response against each type
What are the different types of vaccines?
- live, attenuated
- Killed, whole organism
- Sub-unit vaccines
Name examples of killed, whole organism vaccines
e.g. pertussis, flu (old type), polio (Salk type), cholera, HepA
What are the considerations of a killed, whole organism vaccine?
reactogenicity
boosting required
What are subunit vaccines composed of?
Individual components
- proteins
- toxoids (diphtheria; tetanus)
- peptides (synthetic)
- polysaccharide
- recombinant proteins (cloned into bacteria / yeast)
- subcellular fractions
- surface antigens
e. g. Hep B; Flu H; menB - virulence determinant
e. g. aP-pertussis:- adhesin + toxoid + OMP
Describe the effectiveness of polysaccharide subunit vaccines
Poor antigens
Conjugated to toxoid + outer membrane protein (e.g. MenC; Hib;)
What are the effects of bacterial toxins?
Toxin normally causes direct tissue damage and disease e.g. tetanus , diphtheria
What is a toxoid?
By purifying the toxin and activating it chemically, we produce a toxoid - used in vaccine
What is the effect of toxoids on the body?
Toxoids neutralise toxins when exposed
Why are bacterial capsular polysaccharides poor antigens as vaccines?
short term memory
no T-cell immunity
Why are bacterial polysaccharides less immunogenic in children <2yrs?
Poor IgG2 responses (IgG2 promotes opsonisation
and major recognition of polysaccharides; also B cells less mature)
How is bacterial polysaccharides immunogenicity increased?
Enhance immunogenicity by protein conjugation with toxoids D/T + outer membrane proteins
How does conjugation of bacterial polysaccharides effect the immunogenic response in children?
Long lasting immunity and response in children
Name examples of conjugated vaccines
Neisseria meningitidis Group C MenC vaccine
Haemophilus influenzae Type B Hib vaccine
How does conjugtion work?
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
Outline how bacterial polysaccharides act as antigens
> poor memory
Polysaccharide binds to B-Cell Receptor, but children <2 recognise PS very poorly ∴ produce v. poor antibodies due to poro recognition and no memory associated
How do conjugates act as antigens?
> good memory
By linking PS to a protein, the B cell recognises the protein well and will present it to a T cell
What is the role of CD4 T cells activated by conjugates?
The Th cells recruit cytokines that aid the B cell to produce high affinity antibodies at higher levels - potent response
What are adjuvants?
Chemical / lipid structures that enhance the immune response using the vaccine components
What is the effect of vaccine adjuvants in delivery of immune response?
- enhance immune response to antigen
- promote uptake and antigen presentation
- stimulate correct cytokine profiles
Name an example of an adjuvant
Aluminium salts (Alum)
- form trapped particles (depot)
- slow release of Ag
- large number of Mp’s exposed
Outline the features of a live attenuated vaccine
- Long lived immunity
- Good immune response; IgG, IgA; CMI
- Requires cold chain
- Insufficient attenuation
- Reversion
- Immunosuppressed; Risk of persistent infection
- Foetal damage
Outline the features of a Killed, whole vaccine
- Short or long lived immunity
- IgG - needs boosters
- Poor CMI
- Stable
- Inactivation and immunogenicity
- Contamination
- toxicity/allergy
- Autoimmunity
