TM: Immunisations - Past & Future (ii) Creating a Vaccine
1) Making one
Whole-cell killed
not really for dangerous pathogens
e.g. rabies
must make sure it's completely killed
Live attenuated
not really for dangerous pathogens
subunit
conserved sequences: glycoprotein
immunogenic
adjuvants (antibodies or T cells)
DNA plasmids (works in Guinea pigs)
vectored - e.g. chimpanzee adenovirus 5 (has gone to Phase 1 study)
use studies of partial protection
antibodies correlation with survival
neutralising Ab, how much? to which antigen?
passive transfer experiments
CD4 helper cells
CD8 cytotoxic cells
combo of any of these
2) Candidates
3) Pre-clinical trials
animal model
mice
guinea pig
hamster
non-human primates
cynomolgus
rhesus
baboons
African green
some pathogens only infect certain species
stability
temp
time
purity, toxins, contaminants, LPS
immunogenicity
Ab levels
neutralising Abs
T cell responses
Toxicity + pathology
by law must be done in 2 species (HPRA)
e.g. mice + rabbits
find LD50
distribution (where in the body does it go)
sometimes efficacy @ this stage
4) Clinical Trials
Phase 1
immunogenicity + tolerability in humans
must get ethical + regulatory approval 1st
Phase 2
efficacy, dosing
likely no trials in humans
deployment based in safety + immunogenicity in humans, efficacy in animal models
Phase 3 licensing trials
5) Licensure
6) Manufacturing, marketing + distribution