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