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

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1 P01 A143042-01 6 SEP
Ho, David D.
combination(s) of the 20 possible ones will induce the broadest and most
potent cellular and humoral immune responses in macaques. All of the projects
will converge in the selection of immunization strategies which will be
conducted in macaques in the last years of the proposal using SHIVs containing
HIV clade C envelopes. Three cores are proposed - molecular virology,
immunology, and a primate facili.
This application prompte considerable discussion and difference of opinions
among the members of the peer revie on
/ included: (1) the clearly written proposal with an integrated approach to the
stated objectj ves of the Program Announcement; (2) the development of a cla
SC SHIV to beiused in the macaque model; (3) efficient and economical
experiments designed to answer critical questions concerning the mechanism by
Swhich protective immunity is achieved in the SIV delta-nef.-o SHIV 89.6,macaque model, 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 determine 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 application was also flawed by some serious
weaknesses, namely: (1) it was noted that many of the proposed experiments
outlined in Project 1 are not novel and had already been performed; (2) there
were serious concerns about the degree to which class I would be shut down in
the SIV-ICP47 experiment; (3) there was no provision for testing lymph nodes
or mucosal immunity in any of the in vivo experiments. A number of reviewers
thought that the choice of a clade C HIV was made for reasons not entirely
scientific, and several reviewers have also voiced concerns that SHIV with
non-B, macrophage-tropic HIV envelopes were already in development in other
laboratories. There were also concerns regarding the necessity of developing
yet another SHIV model at all.
There has been a broad-based consensus in the overall comments of reviewers
regarding the application, that while the application is written well and
presents an extensive overall rev" " 9 done throughout the.. and Europe, yet, a number o other researc ou which have already
7 precede se areas of research, were either not noted, included or
)4., were ignored. Furthermore, there was a serious concern that some of the
participating investigators from the Aaron Diamond AIDS Research Center have
no extensive experience in many of the experiments designed at engineering of
the clade C vaccines. In addition, a number of committee members have
suggested that ADARC should take 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.
With rd to the requested budget, all reviewer essed concerns that the
olecular virology core could not possibly do what it wa charged with, by
Conti nued