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

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1 P01 AI43042-01 11 SEP
Ho, David D.
infection. The novel approach of using a SIV-ICP47 construct to determine the
role of cell-mediated immunity in protection from challenge will be
informative, if it works. For the most part, technical assays and reagents
are in-hand and are already being used by the investigators.
However, there was little evidence of testing for anamnestic humoral immune
responses as a potential correlate of protection, and there are no provisions
to test for mucosal immunity, either humoral or cellular, or to test lymphoid
tissue. The investigators acknowledge that their CTL assays may have to be
optimized and they offer three different methodologies. Breakthrough viruses
are apparently- assumed to have escaped from neutralizing antibodies; they may,
however, be GTL escape mutants. It may prove difficult to insert ICP47 into
SIV. No alternative approach is suggested in case problems arise in this
experiment.
The investigators have outstanding qualifications to conduct the proposed
v work, except for the following concerns. Who is Dr. Jin who, according to the
Molecular Virology Core description, is supposed to work on the SIV-ICP47
project? He is not listed in the budget nor is his biosketch provided. Does
Dr. Chen have enough molecular experience to perform the experiments he is
charged with - MVA vaccine, SIV-GFP, and SIV-ICP47?
The facilities, in terms of both space and equipment, are excellent to perform
the proposed experiments.
This reviewer was unable to determine the budget as presented.
REVIEWER C: The goal of this project is to use observational and
interventional experiments to fully characterize the immune correlates of
protection associated with live attenuated SIVmac-delta-nef vaccine. This
focus is the primary strength of this project because even though protective
immunity has been the object of considerable research effort by the scientific
community, it is still poorly understood. The approach is scientifically
important because, in terms of protection, the live-attenuated SIV vaccine has
displayed the most consistent and encouraging results. These studies will,
therefore, contribute to the dual scientific objectives of both understanding
the interaction between SIV and the immune cells it destroys, and to the
developing of an effective and safe HIV vaccine. The proposed studies are
broad-based and comprehensive, testing a variety of concepts in parallel in a
series of small analytical experiments. The methodology is a balanced
combination of technical and empirical approaches, and will adequately address
the stated objectives of the project. The Principal Investigator is
" exceptionally well qualified to carry out the proposed reswarch, wita long
and reievant publ cdtion history. Key staff are fully qualified and capable
of compleing the proposed study. The available resources are centrally
located, facilitating integration among various team members.
In summary, this project is designed to explore a variety of concepts
associated with the immune correlates of protection from SIV in a series of

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