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Now, let me ask the
question, can the same principles,
somewhat complex, that I've just
walk you through that we've used
to create an HIV vaccine be applied
to produce a vaccine to prevent
the acquisition or transmission
of sound falciparum malaria,
the most virulent and
lethal form of malaria.
This disease is transmitted
by the bite of mosquitoes
that contain infectious parasites.
The problem, then, is infection
with Plasmodium falciparum,
the proper name of the
falciparum malaria parasite,
can induce immunity to the
red cell stage of the disease,
reducing its severity.
But that infection does not
prevent infection or transmission.
In other words, just
like for HIV, we
have to have a vaccine that is
better than natural infection
at inducing protection.
That is, the challenge to
prevent infection or transmission
of the infection to others is
that the vaccine must be more
protective than natural infection.
It must induce an
unnatural form of immunity
to relatively invariant pre red
cells stages of the parasite,
or stages of the parasite called
gametocytes that are transmitted
into other mosquitoes, and are
then ultimately in that mosquito
turned into new parasites that
can affect another individual.
And those antigens are not targets
of natural immunity in infection.
1:37
So in order to induce a
pre-erythrocytic vaccine
for malaria, we need
a vaccine that's
better than natural infection.
What do we have that
gives us hope and optimism
that this is achievable?
Well, we have a great advantage
here over situations such as in HIV.
It's actually possible to
challenge humans with malaria
and then to treat them if they
become infected so that we can ask,
can we give an individual a
vaccine, intentionally infect them
with malaria through
mosquito bites, and determine
if that vaccine has protected them.
This challenge model has
allowed the iterative
testing, de-risking, and
advancement of vaccine candidates.
Moreover, using such a model, more
than 30 years ago it was shown
that protection can be achieved.
Initially, that was achieved
by having volunteers who
would be challenged
bitten by more than 1,000
malaria-infected mosquitoes.
And that type of vaccine,
containing irradiated parasites
within the mosquito so that
they could not produce disease,
provided greater than
80% sterile protection.
That is, protection from infection,
whereas natural infection
provides no such protection.
Moreover, more recently, a
similar degree of protection
has been achieved with five
intravenous injections of 100,000
irradiated sporozoites, or
with as little as 45 bites
from infected mosquitoes
followed immediately
by treatment to prevent red cell
stage parasitemia from occurring.
Unfortunately, neither of
these whole parasite approaches
is practicable or scalable for
use in research limited settings.
However, there is a
potential practical vaccine
candidate on the horizon.
A vaccine known as RTS,S which
is composed of a circumsporozoite
protein, abbreviated here as
CSP, has been developed through
a committed partnership
between academics, US military,
and industrial partners who've
worked together for more
than 20 years on this project.
That vaccine has been shown
in field trials in Africa
to provide 30% and 50% protection
from clinical and severe malaria
in infants and young
children, respectively.
However, the problem is that
we'd really like a vaccine that
was more than 80% effective
and provided durable protection
in individuals at risk.
How might we achieve that?
