Friday, 25 October Conference Call on AIDS Vaccine

Research Committee 25-Oct-96 Page 8

correlates of immune protection from infection or AIDS. I don't believe that we
know enough about the immune system or the immune response to HIV infection
to succeed at "rational vaccine design" any time in the next decade or two.
"Nevertheless, the vaccine enterprise needs to maintain a balance between
enough basic research to characterize the underlying mechanisms, and empirical
testing aimed at demonstrating efficacy. But it is probably the latter that will
make the former possible. As an investigator with NIH funding to work at both
ends of the spectrum, I feel that the current mix of basic research, clinic-based
cohort studies, and clinical trials is reasonably well balanced. What is missing is
good product development.
"Despite a general endorsement, I do think there have been two flaws in the
NIAID vaccine development and testing program. The first is that priorities have
been driven too much by theory (or shall we say dogma) and by the overinterpretation of in vitro results, with uncertain biological relevance. It seems that
the NIAID has become aware of this and has recently embraced what they call
"reasoned empiricism," rejecting the idea that we can learn enough to get a highly
vaccine in the first efficacy trial. The second problem is that the vaccine program
is dependent on traditional NIH "academic peer review" which is designed to
select "scientifically novel" approaches and give low priority to the application of
established methods (e.g. whole inactivated virions, split vaccines, purified native
subunits, etc.). In my own experience, a proposal to apply traditional whole killed
virus methods to HIV received a lukewarm peer review with many comments
about the need for more sophisticated "hypothesis-driven" interpretation of in
vitro results. The most recent NIH vaccine development initiative was a Program
Announcement, with no set-aside funds, which once again targets only novel
approaches to vaccine design. Given this bias and the centrality of the peer review
process within the NIH culture, it is unlikely that these historically successful
approaches will ever obtain NIH support.
"That brings me to my favorite soap box.... I think it is unconscionable that
after 12 years of vaccine research, there has been no serious attempt to qualify a
preparation of whole killed virus for human testing as a prophylactic vaccine
candidate. I simply cannot understand why this proven technology which was the
most obvious place to have started has been sidelined for so long. When I talk to
my friends at NIH I get one of several answers to this question. Here they are