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

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1 P01 A143042-01 16 SEP
Ho, David D.
The facilities, both in terms or space and equipment, are outstanding and
appropriate.
The budget, as written, can termned.
Human Subjects: code 10
Gender and Minority Representation: not applicable
Animal Welfare: code 30
Budget: As resented, the proposed budget is incomplete, lacks details, and
therefore cannot be evaluated.
IRG Action: This project, ived a priority score in the very good range
with a numerical value o249.
Administrative Note: The proposed budget for Project 2 is incomplete and lack
details. It is recommended that the applicants submit a complete and detailed
budget.
PROJECT 3: Priming With Recombinant Vaccinia or DNA Vaccines followed by
Boosting Hith Pseudovirions or Envelope Proteins
Critique: The comments below represent essentially unedited comments from the
reviewers of this application. They are included to indicate the range of
comments made during the discussion, and may not reflect the final thinking of
the committee. The RESUME and OVERALL CRITIQUE sections above summarize the
final opinion of the committee after the discussion.
REVIEHER A: Project 3 of this application is designed to deal with the
optimization of humoral and cellular immune responses to HIV/SIV protein
components in experimental animal models through a series of "prime-boost"
experiments. The proposed priming immunizations will employ new vectors
capable of intracellular expression of viral antigens and will induce T cellmediated immune responses, including CTL. Boosts will be performed with new
variants of soluble HIV/SIV proteins and will stimulate B cells to produce
neutralizing antibodies. Specific aims include construction of new delivery
vectors based on recombinant vaccine viruses/pseudovirions and new DNA-vaccine
plasmids, limited testing of immunogens, adjuvants, and liposomes in vitro and
in small animal model (guinea pigs) and monkeys (macaques), and testing of the
most promising priming and boosting combinations in the expanded experimental
series involving macaques. This project, to be jointly supervised and
executed by ADARC staff under the direction of Dr. D. Ho, draws on the
enormous body of systematic and anecdotal knowledge accumulated by these
researchers and by their collaborators and/or competitors over the period of a
decade. As pointed out by the Principal Investigator, the design of the
proposed studies is iterative. The laboratory-based research program will be

Continued