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

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1 P01 A143042-01 5 SEP
Ho, David D.
divided into Core 1: Molecular Virology, Core 2: Immunology, and Core 3:
Primate. All of the projects and cores are located at either the Aaron
Diamond AIDS Research Center or the Animal Models Laboratory, allowing for
easy access to the core facilities. The overall objective of the Molecular
Virology Core (Core A) is to provide comprehensive molecular biology services
[DNA sequencing, HMA/HTA assays, phylogenetic analyses, plasmid preparation,
in situ PCR/immunochemistry), virology services (virus quantitation and
production, titration, assays and tests], reagents, biosafety level 3, and PCR
facilities to members of the Program Project.
The Immunology Core (Core B) is designed to provide comprehensive immunologic
services, regents, and facilities to other investigators in the Program
Project. The investigators will assess the quality and quantity of humoral
and cellular immune responses following immunization and challenge. The
following services will be provided: neutralization assays;antibody
titration, oligomer binding assays, antibody-virion complex assays, generation
of bulk CTL cultures and epitope mapping, CTLp quantitation, TCR repertoire
analyses, MHC typing, complement deposition and ADCC, antibody isotype
determination, cell responses, class I expression evaluation, CD8+ suppressor
factor, cytokine assays, dendritic cell generation and characterization, and
immunohistochemistry.
The Primate Core (Core C) will provide support to investigators from the three
projects in doing SIV/SHIV studies in rhesus macaques. The operation of the
facility, the Laboratory for Experimental Medicine and Surgery in Primates
(LEMSIP), which is located in Tuxedo, NY, is being negotiated with ADARC which
has had an active primate laboratory at this center since 1993. A full time
staff consisting of animal research technicians and two veterinarians provides
the necessary animal care. Experimental protocols for primates are reviewed
monthly and the Institutional Animal Care and Use Committee inspects the
facility three times a year. The laboratory is prepared to house singly-caged
macaques under biosafety level "2+" conditions.
OVERALL CRITIQUE: The overriding theme of the proposed studies is to develop
a vaccine based on HIV subtype C using a prime and boost strategy.
Specifically, rhesus macaques infected with a SHIV chimera containing the
envelope gene from HIV subtype C will be used to test different immunogens,
adjuvants, and vaccine strategies in an iterative process. Early in the
proposed studies, work will entail determining the correlates of protective
immunity elicited in rhesus macaques immunized with a nef-deleted SIVmac
(Project 1), identification, characterization and modification of candidate
subtype C viruses (Project 2), and construction and comparison of poxvirusbased (MVA) or DNA-based vaccines as well as different adjuvants (Project 3).
The best candidates for vaccine development from this early work will be
tested further by construction and testing of SHIV-clade C vaccine candidates
(Projects 2 and 3), antigen boost testing in vivo (Project 3), and basic
research in correlates of protection (Project 1). Using the best available
adjuvant systems, four priming vectors (two vaccinia-based and two DNA-based)
will be combined with the five best antigen boosts to evaluate which

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