Scientific Basis of Vaccines

Question 1

Scientific Principles from Jenner’s experiments

Answer 1

Challenge dose – proves protection from infection
Concept of attenuation
Concept that prior exposure to agent boosts protective response
Cross-species protection – antigenic similarity

Question 2

Eradication of smallpox - how

Answer 2

How ?
Vaccination programmes
case finding (surveillance)
and movement control

Question 3

Eradication of smallpox - why possible

Answer 3

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

Question 4

Vaccine - define

Answer 4

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

Question 5

Vaccine - aims

Answer 5

Protection of the individual ↓rate/severity
Protection of the population Herd Immunity
Eradication of disease

Question 6

Herd Immunity – memory boosted by

Answer 6

Herd Immunity – memory boosted by
periodic outbreaks of disease in community
vaccines

Question 7

Effect of disease rates declining

Answer 7

As disease rates decline - no natural boosting

Increases importance of vaccination take up rates

Question 8

Primary exposure - characteristics

Answer 8

5-7 days antibody response
2 weeks for a full response
IgM to IgG switching memory B and T cells

Question 9

Secondary response - how many days for full response

Answer 9

2 days for full protective response

prior exposure

Question 10

Post-exposure immunoprotection due to

Answer 10

Post-exposure immunoprotection due to response vs specific antigens
e.g. surface proteins, polysaccharides, toxins
good targets for vaccine candidates

Question 11

Vaccines : general principles

Answer 11

Induce correct TYPE of response
Induce response in RIGHT PLACE
Duration of protection
Age of vaccination

Question 12

Most antigens are immunogenic but NOT immuno-protective - why

Answer 12

Why? Can’t predict

Question 13

Serology can what

Answer 13

Serology can differentiate exposure from vaccination

e.g. Hep B - viral surface antigen

Question 14

Types of Vaccines I - Live, attenuated organism - define, examples of when used and how is it formed

Answer 14

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

Question 15

Polio (Sabin) - types and number of mutations

Answer 15

Polio (Sabin) Type 1 has 57 mutations;
Type 2 & 3 only a few.
Possible to revert (wild-type in nappies !)

Question 16

Polio (Sabin) - reason for 3 doses

Answer 16

3 separate doses to overcome strain antagonism and ensure adequate immune response against each type

Question 17

Types of Vaccines II - define, examples of when used + requirements

Answer 17

2. Killed, whole organism
   e.g. pertussis, flu (old type)
   polio (Salk type), cholera, HepA
   reactogenicity
   boosting required

Question 18

Types of Vaccines III - components

Answer 18

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

Question 19

Describe processing of toxin to form vaccine

Answer 19

Inactivation with formaldehyde = toxoid

Toxoid = Antigenic and non-toxic

Question 20

Bacterial Capsular Polysaccharides as vaccines = -ves

Answer 20

Poor antigens short term memory
no T-cell immunity
less immunogenic in children

Question 21

Bacterial Capsular Polysaccharides as vaccines = enhancing of immunogenicity

Answer 21

Enhance immunogenicity by protein conjugation
toxoids D/T + outer membrane proteins

long lasting immunity and response in children

Question 22

Conjugation - function

Answer 22

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

Question 23

Vaccine Adjuvants and Delivery Systems - effects

Answer 23

enhance immune response to antigen
promote uptake and antigen presentation
stimulate correct cytokine profiles

Question 24

Vaccine Adjuvants and Delivery Systems - example of action

Answer 24

e.g.
Aluminium salts (Alum) : form trapped particles (depot)
slow release of Ag
large number of Mp’s exposed

Question 25

live, attenuated vaccines - characteristics

Answer 25

long lived immunity
good immune response		
(like infection)
IgG, IgA;  CMI	
requires cold chain
insufficient attenuation
reversion
Immunosuppressed 			
(risk of persistent infection)
foetal damage

Question 26

Killed, whole vaccines -

Answer 26

short or long
IgG   (needs boosters)
poor CMI
stable
inactivation and immunogenicity
contamination 
toxicity/allergy
autoimmunity