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Interview
with Doctor Robert Gallo—
Is Sterilizing Immunity Necessary to Prevent
HIV Disease?
Dr.
Robert Gallo, co-discoverer of the HIV virus, is Director
of the Institute of Human Virology in Baltimore, MD
Searchlight:
Some viral products like nef, Tat, and vpr, are toxic
to cells and compromise immune function. Even if we can control
HIV while it continues to remains in the body, will it also
be necessary to attack these viral proteins somehow?
Gallo:
I cannot say it is necessary; I do not know that it is necessary,
but I certainly think it is a strategy that needs to be focused
on. I think it's sensible, and what information I see indicates
that it will be a useful approach. And I don't think it gets
enough attention, but everything from animal models to in
vitro data to what little clinical data is available, argues
that this is a very worthwhile approach.
There was resistance in some of the academic community to
the notion that Tat would be circulating in enough amounts
to cause problems. But Tat doesn't have to be in high concentrations,
to cross the membrane into the cell nucleus to activate cellular
genes. It's turning out to do things by just binding to cell
membranes. And very little amounts can make a major impact.
And I think the data is virtually conclusive at this point
that it's important.
So
we may have to look for select populations, and/or couple
it with drug therapy (to study this further).
Searchlight:
I think that might be a problem with studying new kinds of
approaches, finding those select populations that are appropriate
for these studies. How do you think that will impact the development
of new concepts?
Gallo: My guess is, very seriously so.
For ethical reasons, one is almost compelled to limit new
approaches to those people who absolutely refuse drug, or
are totally resistant, or maybe in very late stage for one
reason or another. This population is unlikely to respond
favorably to an approach that would work well in healthier
people, so potentially beneficial options will remain unproven.
Searchlight: I was struck by an idea from Neal
Nathanson's talk when he suggested that we may not need sterilizing
immunity from a vaccine, but that partial immunity might suffice.
Gallo:
First, about Neal's comments. when Neal made the analogy (from
vaccines) to drugs, as I pointed out, that analogy does not
hold. Drugs are something where you know what you're getting.
Searchlight:
Just to make sure we're on the same page, what's the
analogy you're referring to?
Gallo: He was pointing out that people on combination
chemotherapy, who have suppressed the virus to very low levels
are doing fine, therefore, maybe we should have an immune
response (to vaccine) where we can consider having a low level
of virus as being acceptable. But when you ° don't know the
immune correlate to give, then you don't know how to keep
the virus suppressed, so that breaks down immediately, logically,
in my mind. I'm worried about it. I'm worried about it because
what happens is what I think will happen, namely the suppression
won't last that long.
Searchlight:
And you can't keep people indefinitely on HAART
Gallo:
I don't think we've made a strong enough attempt to produce
sterilizing immunity.
There's
a limitation: we don't have a small animal model. Of all the
fancy reasons we give for the block of an AIDS vaccine, the
singular most important reason is that we don't have a rapid,
simple, widely-available animal model. We have an animal model
(Editor's note: a primate model) that's good, but it's not
so simple, not so inexpensive, and it's certainly not widely
available.
Searchlight:
Do you think perhaps people are giving up quickly on the idea
of sterilizing immunity due to a sense of impatience, that
there are so many factors to be learned about why some people
may be exposed multiply but not get infected?
Gallo:
Of course. What other reason? What other reason can there
be? I don't want to say that I am sure why they are vocally
against it. I just want to make sure that we have tried hard
enough for sterilizing immunity.
That's
the standard for our Institute. That's going to be the demand.
I'm not going to let people say, oh we have a vaccine, we
can afford to just reduce the virus a lot. We will stay with
trying to get sterilizing immunity. Now, one does have to
get funding, and we do have reasonable funding for a vaccine
program now, but if the field turns against that idea (that
we need to elicit sterilizing immunity ), we might have future
problems.
Our focus is on mucosal immunity, using chemokines as potential
immune correlates, vaccinating to include immunogens that
are regulatory genes, and going for sterilizing immunity.
These are the tenets of our vaccine program.
Going
back to therapy and the needs of the Third World: we've got
to find things that can be given once in a while, like a vaccine
therapy. Such approaches, I think, will come out of a better
understanding of pathogenesis. Next year's Keystone meeting,
which I am organizing along with (Dr. Joseph) Sodroski
(of Harvard Medical School) and (Dr. Didier) Trono
(of the University of Geneva, Switzerland), that's
going to be the topic.
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