Summary Statement: ADARC Program Project on HIV/SIV Vaccine Development

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1 P01 AI43042-01 2 SEP
Ho, David D.
and three service cores, is aimed at conducting preclinical and animal-model
research towards the development of practical immunogens that may constitute,
or contribute to, an effective prophylactic vaccine against HIV-1 infection.
This application prompted considerable discussion and difference of opinions
among the members of the peer-review panel. Key strengths of the application
included: (1) the clearly written proposal with an integrated approach to the
stated objectives of the Program Announcement; (2) the development of a clade
C SHIV to be used in the macaque model; (3) efficient and economical
experiments designed to answer critical questions concerning the mechanism by
which protective immunity is achieved in the SIV delta-nef or SHIV 89.6
macaque modet, in particular the PMPA experiment to determine the role of
ongoing replication in protection; (4) the predictable, yet important,
experiments to improve the prime and boost vaccine strategy;. and (5) the
intent to go beyond basic CTL and antibody assays to determie the correlates
of protection. There was clearly synergy between projects with data from one
project being fed into another, culminating in the final experiment where the
best vaccine strategies would be tested in the clade C SHIV model system.
However, as presented, the a lication was also flawed by some serious
weaknesses, namely: (1) was note that many of the proposed experiments
outlined in Project re not novel nd had already been performed; (2) there
were serious concer out th ree to which class I sh down in
the SIV-ICP47 experiment; (3) there was no provision f testing lymph nodes
or mucosal immunity in an of the i perime ns. some
reviewers, the ce of a clade C HIV was made for reasons not entirely base
on scientific owledge since r "re is 1te evidence to support
that subtypes are re evant to human immunity, and consequently, vaccine
development. Many reviewers have also voiced concerns that SHIV with non-B,
macrophage-tropic HIV envelopes were already in development in other
laboratori ere w e 1 concerns expressed whether it is necessary to
develo yet another SHIV model t all.
In the overall comments of reviewers regarding the application, there has been
a broad-based consensus that while the application is written well and
presents an extensive overall review of what h done throughout t.S.
and Europe with regard to HIV vaccine developmen yet, a number of other
researchsearc ere
eith not noted, included, or were ignored in this o rall review.
Furthe e there was alo a serious conce ssed that some
participating investigators from AD ave ne xensive experi ce in many of
the experiments designed at engin ering of clade C vaccines. In ddition, a
number of committee members have sug ake the lead and
collaborate with research groups that are already preceding ADARC in these )
areas of research by using immune assays developed by the Aaron Diamond AIDS.
Research Center.
In summary, in a broad-based majority, members of the review panel perceived
the significance of the overall Program as limited because, in their opinion,
(1) it is mostly variations on already well-studied hypotheses; (2) it
emphasizes the development of another SIV model; and (3) it lacks a clear-cut

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