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Printable Handouts
Navigable Slide Index
Topics Covered
- Vaccine pharmacology
- Vaccine immunogenicity
- Vaccine challenge-protection studies
Links
Series:
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Therapeutic Areas:
Talk Citation
Sheets, R. (2015, December 31). Vaccine preclinical studies 2 [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 14, 2024, from https://doi.org/10.69645/MCQV3599.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Rebecca Sheets has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Vaccine preclinical studies 2
Published on December 31, 2015
20 min
Other Talks in the Series: Vaccines
Transcript
Please wait while the transcript is being prepared...
0:04
Now we're going to move
from the vaccine's
safety aspects
or toxicology,
to the pharmacology aspects,
or proof-of-concept.
This is the flip side of safety.
So safety is the way
we try to identify risks
and assess risks,
and the proof-of-concept studies
or mode-of-action studies,
are how we try to assess
the potential for benefit.
So for drugs,
pharmacology encompasses
the concepts of pharmacokinetics
and pharmacodynamics.
But in fact for vaccines,
those concepts
don't really readily apply
and what we're really trying
to address is the immunological
mechanism for protection.
So we look at
immunogenicity in animals
and if there's a relevant
animal model,
then we try to do studies
of challenge-protection.
And I'll explain those
in more detail in a moment.
Often these types of studies
are research studies.
And in fact, they're rarely,
if ever, performed
in compliance with
good laboratory practices.
So even though they're
intended to support
regulatory decision making
about potential for benefit,
in fact, the fact
that they're not required
to meet these good
laboratory practice regulations
reflects the fact that,
in fact, in the US,
Phase 1 studies
can only be placed
on clinical hold for safety.
And so really the regulatory
decision making,
the precision
around that has to be
on the basis of risk
assessment or safety aspects.
1:37
Vaccine immunogenicity
is key to understanding
whether or not a vaccine
has any potential
to work in humans, and often
we'll use an animal model.
It's important
that these involve
a relevant animal model
although sometimes
it's not easy to identify.
And, in fact,
often what people will do
is move from small animals
like mice or guinea pigs
to slightly larger animals
like rabbits
and then to non-human primates.
However, if the vaccine
is one that replicates
as a live vaccine,
then you need an animal model
in which it will also replicate
and replicate
in the same tissues
that it would in a human.
If the vaccine incorporates
some species-specific molecule,
for example, DNA vaccines
or some vectored vaccines
will include a cytokine.
For example, cytokine
encoded in a plasmid to include
as an adjuvant for the vaccine.
And you may need
to use an analogue
in a species of choice.
For example, if you're
looking at a Rhesus cytokine
in a Rhesus Macaque to mimic
human cytokine in humans.
However, often there is
more than one animal model
used as I explained,
and usually people
start small and then
work their way up.
And I'll talk to you in a moment
about the limitations
of that approach.
But the purposes of these
vaccine immunogenicity studies
really are all around exploring
what doses might be needed
in order to get an immune
response in human.
Here, especially if you're using
a small animal,
you will scale the dose.
So, for example, you might
use a concentration
that is the amount available
in 50 micro liters in mice,
whereas you would give
half a mil or a mil in humans.
You might want to explore
various aspects of your regimen,
so for example, maybe you
need to prime-boost approach.
Maybe you need more
than one inoculation
in order to optimize a response.
You may need to
explore the timing
between the inoculations,
often a rest period
is required to really get
an anamnestic response
to your immune response.
And also you want
to be able to look
at whether or not you
can achieve durability,
although sometimes
for some vaccines a rapid
onset of protection
may be more important
than a durable protection.
You'll also explore
in the animal models
routes of administration.
These might intramuscular,
subcutaneous,
a dermal route, intranasal, oral,
or some other
kind of mucosal route.
Some people use, for example,
suppositories to try to deliver
to mucosal surfaces.
This is also a good
juncture in which to explore
whether or not you
need to add an adjuvant.
And there will be a separate
lecture in this series
on vaccine adjuvants,
but the purpose of adjuvants
really are to determine
whether or not you can spare
dose of the vaccine,
whether you can modulate
the immune response
to change its character
to be one that's more
protective or to potentiate
the immune response
to drive it higher
than you would be able
to do without an adjuvant.
And, of course,
you want to explore
the types of immune
responses and the level
of immune responses
that you can get
in the animal model
with the vaccine.