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

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1 P01 A143042-01 7 SEP
Ho, David D.
relyin only on Dr. Cheng-Mayer at 15 percent effort and a "To be named"
te nici percen e or rovide the proposed services. Since no
in idual budgets were given for any f the projects it was difficult to
judge who would be doing what w and how much money would be devoted to each
pr.
Summary of Comments by Reviewers on the Scientific and Technical Merits of the
Overall Application: Following is a summary of written comments by members of
the peer review panel on the scientific merits of the overall application made
during the discussion. As presented, these comments reflect the opinion of
the majority -p-f reviewers.
The main objective of this P01 application is to make an improved liveattenuated SIV vaccine to...form the basis for hypothesis refi-nement, e.g., if
a successful vaccine is made, then it will supposedly serve a a template for
a human HIV vaccine. The proposed approaches are: (1) to attempt to dissect
the correlates of immunity in a SIV vaccine model (adapted from Dr.
Desrosiers' SIVmac-delta-nef model); (2) to develop a better env construct to
induce neutralizing antibodies; and (3) to follow the prime-boost concept,
e.g., stimulate cellular immunity (primarily CTL's) with a vaccinia construct
or DNA construct followed by stimulating humoral immunity with a modified
envelope protein.
The major overall strengths of the application are:
(1) the intention to develop a better env construct to induce neutralizing
antibodies. Although neutralizing antibodies appear to play little role in
controlling infection in humans, this hypothesis is worth testing since an
"unnatural construct" may induce protective antibodies;
(2) the proposed follow-up of the prime-boost concept; that is, to stimulate
the cellular immunity (primarily CTL's) with a vaccinia construct or DNA
construct followed by stimulating humoral immunity with a modified envelope
protein. This is a long-debated hypothesis that has yet to be proven
effective but still remains worthwhile pursuing since it could lead to
synergism between cellular and humoral immunity. This approach has proven
safe, immunogenic, and "protective" in non-human primate models and is
presently in human Phase 1 trials.
However, the proposed studies, as described, suffer from a number of serious
weaknesses which significantly diminished the enthusiasm for this application,
namely:
~ \ (1) there is very little novel concepts in this application and most of the
proposed studies have already been done previously (and also by more than one
qualifi es iga or
( the relationship or correlation of a SIV model for ccine effectiveness
must be validated for human disease just like any other 1 boratory test.
Therefore, defining the intricacies of any animal model efore determining its
correlation to human vaccine effectiveness is que o nable. In the opinion of
any reviewers, expending so much energy o rfecting an animal model is a
weakn. of this Program Announcement to move as";7K
Continued