Scientific Basis of Vaccines Flashcards
Scientific Principles 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
Eradication of smallpox - how
How ?
Vaccination programmes
case finding (surveillance)
and movement control
Eradication of smallpox - why possible
No sub-clinical infections After recovery, the virus was eliminated - no carrier states No animal reservoir Effective vaccine (live vaccinia virus) Slow spread, poor transmission
Vaccine - define
Material from an organism that will actively enhance adaptive immunity
Produces an immunologically “primed” state the allows for a rapid secondary immune response on exposure to antigen
Vaccine - aims
Protection of the individual ↓rate/severity
Protection of the population Herd Immunity
Eradication of disease
Herd Immunity – memory boosted by
Herd Immunity – memory boosted by
periodic outbreaks of disease in community
vaccines
Effect of disease rates declining
As disease rates decline - no natural boosting
Increases importance of vaccination take up rates
Primary exposure - characteristics
5-7 days antibody response
2 weeks for a full response
IgM to IgG switching memory B and T cells
Secondary response - how many days for full response
2 days for full protective response
prior exposure
Post-exposure immunoprotection due to
Post-exposure immunoprotection due to response vs specific antigens
e.g. surface proteins, polysaccharides, toxins
good targets for vaccine candidates
Vaccines : general principles
Induce correct TYPE of response
Induce response in RIGHT PLACE
Duration of protection
Age of vaccination
Most antigens are immunogenic but NOT immuno-protective - why
Why? Can’t predict
Serology can what
Serology can differentiate exposure from vaccination
e.g. Hep B - viral surface antigen
Types of Vaccines I - Live, attenuated organism - define, examples of when used and how is it formed
Live, attenuated organism
(e.g. BCG, polio(Sabin), MMR, yellow fever, VZV )
by:- serial passage,
low temperature adaptation,
recombinant genetics ( S.typhi Ty21a; galE + aroA/B/C mutant)
selection of natural attenuated strains
Polio (Sabin) - types and number of mutations
Polio (Sabin) Type 1 has 57 mutations;
Type 2 & 3 only a few.
Possible to revert (wild-type in nappies !)
Polio (Sabin) - reason for 3 doses
3 separate doses to overcome strain antagonism and ensure adequate immune response against each type
Types of Vaccines II - define, examples of when used + requirements
- Killed, whole organism
e.g. pertussis, flu (old type)
polio (Salk type), cholera, HepA
reactogenicity
boosting required
Types of Vaccines III - components
Sub-unit vaccines (individual components)
- proteins - toxoids (diphtheria; tetanus) - peptides (synthetic) - polysaccharide - poor antigens - conjugated to toxoid + outer membrane protein (e.g. MenC; Hib;) - recombinant proteins - sub-cellular fractions - surface antigens e. g. Hepatitis B; influenza haemagglutinins; menB - virulence determinant e. g. aP-pertussis:- adhesin + toxoid + OMP
Describe processing of toxin to form vaccine
Inactivation with formaldehyde = toxoid
Toxoid = Antigenic and non-toxic
Bacterial Capsular Polysaccharides as vaccines = -ves
Poor antigens short term memory
no T-cell immunity
less immunogenic in children
Bacterial Capsular Polysaccharides as vaccines = enhancing of immunogenicity
Enhance immunogenicity by protein conjugation
toxoids D/T + outer membrane proteins
long lasting immunity and response in children
Conjugation - function
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
Vaccine Adjuvants and Delivery Systems - effects
enhance immune response to antigen
promote uptake and antigen presentation
stimulate correct cytokine profiles
Vaccine Adjuvants and Delivery Systems - example of action
e.g.
Aluminium salts (Alum) : form trapped particles (depot)
slow release of Ag
large number of Mp’s exposed
live, attenuated vaccines - characteristics
long lived immunity good immune response (like infection) IgG, IgA; CMI requires cold chain insufficient attenuation reversion Immunosuppressed (risk of persistent infection) foetal damage
Killed, whole vaccines -
short or long IgG (needs boosters) poor CMI stable inactivation and immunogenicity contamination toxicity/allergy autoimmunity
