IAVI Report Vol. 2, no. 2

We're on a projectory to get higher levels of
CTLs and better immune responses..
Hopefully this study will give 'us more
information about whether to initiate efficacy
studies. But it's not a decision that our
committee has been asked to make.
IAVI REPORT: In terms of 'HIV-DNA
vaccines, how do we move research
forward more rapidly?
BALTIMORE: This approach is actually
moving forward quite rapidly. I've talked'
with researchers developing DNA vaccines
in both 'commercial and academic
laboratories. I visited the lab at Merck and
they appear to have a very orderly and
rational program in place.They want to get
the best vector available and begin
protection studies in monkeys.
IAVI REPORT: You've also spoken about
the need to start looking more closely at
traditional methods of vaccination.
BALTIMORE: That's correct. Almost all
approved vaccines use either wholeinactivated or live-attenuated virus. It would
be a mistake to abandon these approaches,
without taking a very good and careful look
at them.That is one of the responsibilities of
our committee, to insure that every
reasonable approach is pursued.The term
that has been used is to try to let a thousand
flowers bloom.I
IAVI REPORT: Do you think live-attenuated
HIV vaccines will ever be tested in humans?
BALTIMORE: The issue is complicated. So
far, we know that in monkeys given the
attenuated virus, protection against disease
has been extremely impressive. But there are
real safety concerns.That is why the large
safety trials in monkeys that IAVI is proposing
are so important.
There is another possible approach. From
what I hear; there is a cohort of Australians
who received blood from a single donor an'd
have become infected with what appears to
be attenuated HIV Researchers are now
talking about modeling a vaccine on this
attenuated virusThe rationale, as I
understand, is that this virus has already been
effectively tested and followed in humans for
over IO0 years. However; the safety questions

may be so serious that people will not be
prepared to go ahead with human studies of
live-attenuated HIV vaccines.

IAVI REPORT: In terms of real dollars, is'
the U.S. government spending enough
money on AIDS vaccine research?
BALTIMORE: At this point, I have not seen
many very good ideas that are languishing

IAVI REPORT: Thenew NIH vaccine center is
being overseen bya-numbdr of NIH institutes
and conimittees. Is respousibilitytoo diffuse
for things to mov quicd and efficiently?

for lack of funds.
Resources are being
increased at a
reasonable rate. But
we'll see how the
Innovation Grants
work. We may
discover that there is
a huge well of interest
among very good
people who have not
been supported.
IAVI REPORT: How do
you make sure that the
private sector invests
sufficient resources in
HIV vaccine
development?

BALTIMORE

The central issue,
three years from now,
will be whether we
have a more rigorous,
broad-based research
program that is
looking at a wider
range of approaches.
and candidate vaccines.

I don't think that's fairThe
resourcesfor the lab are
coming from two NIH institutes
(NCI and NIAID), both of
which have a good amount of
vaccine expertise.
The.lab director will report
to a committee headed by
Harold Varmus (NIH
Director), and my committee
will serve as the scientific
advisory board. What you
must remember is that the
climate of leadership at NIH is
very different today.The
reason it works so well is
because Harold (Varmus) has
made sure that the directors
are working with each other
There's a real mutual respect.

BALTIMORE: I cannot say that I am
satisfied with the level of investment in the
private sector We may need to provide
some incentives for companies to insure
that multiple approaches are being pursued.
One company that I have not yet spoken
with is American Home Products (WyethLederle Vaccines).They have funded research
on HIV vaccines using adenovirus vectors
and a study of this approach in chimpanzees
was just published. I'd like to know whether
the company plans to continue this research.
If not, I think it's very important for the
government to pick it up.
IAVI REPORT: What about fears that
research funds for vaccines will come out of
AIDS therapeutic or prevention research?
BALTIMORE: Well, our committee doesn't
have any funds to allocate.That's the job of
Bill PaulTony Fauci and Harold Varmus. And
they have said consistently that money for
vaccines will not come from existing
programs. Recently, vaccine research has
seen a greater increase, primarily because
the base was so low. Of course, if we start
doing efficacy studies a lot more money will
be required. So, we're going to need to
figure out what to do.

It's a very different style and a real change.
That's how we were able to get the
Innovation Grants program set up so quickly.
IAVI REPORT: Is it important to have HIV
vaccine development programs that
compete with NIH efforts?
BALTIMORE: Absolutely.When you have a
diversity of funding sources and research
programs the effort is much stronger. It
goes to a very fundamental difference
between the way science is done in the
United States and abroad. Many countries
have a Ministry of Science that tries to
centralize scientific decision making and
funding. In the United States we have
scientific programs in many different
government agencies, as well as in industry
and the not-for-profit sector
That means that if somebody has an idea
and they send it to the NIH and the NIH
says its a lousy idea, that person can go to
other funding sources. Many ideas are
funded that way. And that's terrific,
because it means that there is no
orthodoxy. And it also keeps NIH more
flexible because once NIH becomes too
rigid or orthodox, there will be others to
fund more innovative research.

continued on page 11