DYANN F WIRTH: My name is Dyann Wirth.
And I'm professor of immunology and infectious disease at the Harvard TH
Chan School of Public Health.
I'm here today interviewing Dr. Kent Kester on his work in malaria.
Kent, please introduce yourself.
KENT KESTER: I'm Kent Kester.
I'm a professor of medicine at Unifored Services University
and head of translational science and biomarkers at Sanonfi Pasteur.
DYANN F WIRTH: Can you tell me how you first got involved to work on malaria?
What were your first experiences?
KENT KESTER: It was kind of an accidental thing.
I was an Infectious Disease Fellow in the early 1990s
at Walter Reed Army Medical Center and ended up
working doing my research rotation as an Infectious Disease Fellow
with people who I knew in the Army who ended up working on malaria.
One thing led to another.
And research project ended.
My fellowship ended.
I graduated, stayed on at Walter Reed and ended up
doing malaria vaccine development and more for probably
the next 20 years in the Army.
DYANN F WIRTH: What do you think the biggest R&D
challenges are that we face today and that maybe we've
faced over the last decade?
KENT KESTER: From my perspective, it's--
one of the biggest ones is funding.
We recognize that developing effective interventions,
whether it's drugs or vaccines against malaria, requires sustained funding.
And piecemeal funding, small grants, and awards just don't do it.
And if you're going to develop something that's
going to have a global population-based impact,
it really has to be done at an industrial scale.
So funding is number one.
Number two is sustaining interest on the part of the scientific community.
There's no shortage of research scientists who like to work on malaria.
They have their favorite enzyme, their antigens.
And it's all good stuff.
But the challenge is, is that as sort of the behemoth of scientific funding
and areas of emphasis move along from innovative area to newer innovative
areas, sometimes interest gets lost. .
And so it's important to maintain that interest,
to grow next generation of researchers, and to keep the pressure on
to get things done.
DYANN F WIRTH: So you've been in the military.
And now you're in industry.
And you've been exposed to the World Health Organization
and public-private partnerships.
Can you give us a sense of the roles of these organizations, how they differ
and how they've changed over the years?
KENT KESTER: You know, I think one of the big impacts of sort
of the worldwide malaria research, malaria R&D research, elimination,
eradication campaigns, has been this concept of public-private partnerships.
It's clear that academic groups, while they have great ideas, great science,
a lot of enthusiastic, motivated young researchers,
don't necessarily have the wherewithal to get products across the finish line.
Industry, while it can do things at a big scale,
can get a lot of things made and deployed,
have the regulatory throughput, don't always necessarily
have that spark of early-stage discovery interest.
So that's a disconnect.
Government agencies, nonprofits, I think they tend to fill in the gaps.
And so it really is an important concept of these public-private partnerships.
It's an evolving one.
I think where we are now as to where we were, say, in the early '90s,
we're light years ahead.
DYANN F WIRTH: In thinking about the development, say, of the RTS.S vaccine,
which you had familiarity with as you were working in the military
and now in your role at Sanofi, looking at vaccines more generally,
what made that something to push forward?
As you say, it took a long time.
The RTS,S vaccine was decades in development.
But now it is an effective vaccine in humans.
KENT KESTER: I think there was much work done with RTS,S and its predecessors
for a number of years that didn't really go anywhere-- a lot of failed trials,
small studies, five, 10, 15 volunteers.
And it was really the advent of combining RTS,S, the antigen,
with novel adjuvants that had been developed at that time by SmithKline
Beecham, now GlaxoSmithKline, that really showed for the first time that
effective protection could be achieved.
I think if that hadn't happened, the program probably would have died.
That finding of significant protection, it really--
I don't want to say it put the program on steroids.
But it certainly propelled it better and made
believers of people who previously had thought
that it wasn't going to go anywhere.
DYANN F WIRTH: As you think to the future,
where do you see malaria vaccine development going?
And where do you see it kind of fitting into the overall vaccine development?
The world of vaccines has changed.
And and where does malaria fit in this newer world?
KENT KESTER: It's a great question.
You know, if you look at RTS,S, in many ways, as you say,
it's gone through really decades of work to get where we are now.
It's kind of an old style vaccine.
That's not necessarily a bad thing.
But if we were starting de novo today, we probably
would do things a lot differently.
We have much different insights into malaria immunology, protection
against disease, in some ways analogous to what's
happened on a larger scale in HIV.
So the whole fight against HIV has just developed huge amounts of knowledge
about immunology.
And I think the RTS,S work and allied efforts,
other groups who want to develop another vaccine or have different antigenic
idea, building on the work that the RTS,S program has done,
I think has really helped us a lot.
We have a vaccine that clearly shows some degree of protection.
DYANN F WIRTH: Right.
KENT KESTER: As you say, it has its advantages.
And it has its limitations.
I think now we're at a point where we can take a step back, the field,
and say, OK, how can we make this better?
How can we leverage new technologies, whether it's
genomics or other types of omics things, new ways of interrogating
the immune response and really discerning correlates of protection,
et cetera.
So I think it's really been groundbreaking.
The only thing that's been a bit discouraging,
of course, which goes back to my comment before about funding,
it's taken a long time.
So if you look in the industry, if you have an idea, let's say, for a quote,
unquote "routine vaccine," whatever that means, from idea to approval
to deployment may take 15 to 20 years.
It may cost up to $1 billion for all the trials, all the production,
all that kind of stuff.
And if you look at the amount of funding that's gone to malaria vaccines,
while it's a lot of money, it's not $1 billion.
DYANN F WIRTH: Yeah.
It's a very interesting perspective.
In thinking about vaccines in general, I mean, there's
this push now to get Zikka vaccine.
And we hear that Zikka vaccines will be available really quickly.
So in contrast to this long development period,
what makes that technologically possible?
But also, what makes that possible kind of in an advocacy sense?
KENT KESTER: The big difference is, of course, is malaria is parasite.
So parasites have evolved with us for millennia.
And so they know how to hide out.
They know how to live with us in most cases.
There are multiple antigenic variations of parasites.
So that's part of it.
Zikka, it's one strain.
It's a virus.
We know how to make viral vaccines.
You know, it's fairly straightforward.
And I'm not saying that that's necessarily a slam dunk.
But it's much easier than developing a vaccine against a virus.
There's already been a dengue vaccine that's
been licensed a number of countries around the world.
There is yellow fever vaccine.
And there are other vaccine candidates against other types
of flaviviruses that, in experimental settings, actually work very well.
I think that the concept of getting a Zikka vaccine
technically made and along the approval pathway,
I think that's not out of the question.
I think the bigger challenge for Zikka is, how do you show efficacy
in a setting of perhaps an unstable epidemic, which we still
don't understand, when 80% of the people are actually asymptomatic?
So there's still some unknowns there.
But I think from a technical standpoint, developing
a Zikka vaccine is much, much easier.
DYANN F WIRTH: So in some ways, the vaccine like the yellow fever vaccine,
which was one of the first successful vaccines, led the way.
In some ways, you can think about RTS,S maybe leading the way for malaria
vaccines in the same way.
Because the parasite is much more complex.
So I think that is a very interesting the analogy
to how to think about where we are in malaria vaccine development.
KENT KESTER: Absolutely.
You show some initial protection.
You show initial value.
And if there's a need, hopefully the funders, the advocacy
groups, and the scientists who have the good ideas will be able to run with it.
And I think that's what we're seeing.
DYANN F WIRTH: In terms of eradication, which
is the kind of focus of what we're talking about in general,
do you think the vaccine needs to be there in order for eradication
to be successful?
You know, if I think about it, the diseases
that are eradicated are almost eradicated in the world
primarily are through the use of a vaccine.
So do you think it's possible to eradicate malaria without a vaccine?
And I'd be interested in your thoughts on that.
KENT KESTER: It's an interesting question.
You know, as a vaccine person and as a malaria vaccine person, of course,
I have to say yes, that it's important.
But from a-- when one takes a step back, when we think about controlling,
eradicating, eliminating malaria, a lot of the approaches are low tech, right?
Get rid of mosquitoes.
Diagnose and treat people.
Get rid of standing water, these sorts of things.
However, again, these are parasites.
They're very wily parasites.
They're very persistent.
If one is trying to develop sort of a comprehensive approach
to eliminate malaria, I think there's a role
for a vaccine just as much as there's a role for mosquito control and bed nets
and more.
DYANN F WIRTH: What sort of advice would you
give someone who's kind of early in their career,
or even pre-career, on how to prepare themselves for a leadership role,
as you've assumed in your field?
KENT KESTER: I think part of it is, is don't just limit
oneself to excellence at the bench.
That's really important.
You have to be scientifically credible.
However, if you really want to make a difference,
you' got to understand the issues.
You have to understand, how does a vaccine fit into a larger strategy?
How does that fit into low tech approaches and public policy and WHO
recommendations, et cetera, et cetera?
From a realistic standpoint, they really need
to be engaged just beyond the bench--
understand the issues, make contacts, and really be involved.
And it's not necessarily political advocacy.
It's scientific connectivity and being engaged and being visible.
DYANN F WIRTH: That's a great way to think about it--
having them reach out to others that have complementary skills.
KENT KESTER: Right.
You and I have both dealt with many people in our careers
who have shown interest.
And we've helped point them in those directions.
And I think we can count a number of those people who
are now developing leadership roles of their own,
which is a really good thing.
DYANN F WIRTH: Well, thank you very much, Kent.
This has been fantastic.
KENT KESTER: Great.
Thanks.