During the last three years it has been demonstrated that safe and highly effective RV-based vaccines can be constructed and further emphasize their potential utility as efficacious anti-HIV vaccines. Recent research results indicate that even previous promising HIV-1 vaccine approaches, which prevented an AIDS-like disease in rhesus macaques, failed due to CTL escape mutants. We hypothesize that successful HIV-1 vaccines need strong humoral and cellular immune responses and our preliminary data indicate that such responses can be induced by RV-based HIV vaccines. This grant proposal is directed towards the further detailed analysis of the immunogenicity of RV-based HIV-1 vaccines and the improvement of their immunogenicity. After detailed studies utilizing different methods in a mouse model, promising approaches will be further analyzed in nonhuman primates.
In Aim 1 we propose to analyze RV vectors expressing multiple genes such as HIV-1/SIV GagPol and HIV-1 Env and compare their immunogenicity to vaccines expressing single HIV-1/SIV proteins.
Aim 2 analyzes the potency of the co-expression of cytokines or a pro-inflammatory molecule to enhance the immunogenicity of RV-based vaccine.
Aim 3 is directed toward an efficacy study of the RV-based HIV-1 vaccines in the rhesus macaque model system. Thus, we will pursue several complementary approaches designed to further improve our HIV-1 vaccines, study their anti-HIV directed immunogenicity in detail, and test their efficacy in the rhesus macaque model system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI049153-06
Application #
7190520
Study Section
Special Emphasis Panel (ZRG1-VACC (01))
Program Officer
Pensiero, Michael N
Project Start
2001-03-15
Project End
2009-02-28
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
6
Fiscal Year
2007
Total Cost
$701,155
Indirect Cost
Name
Thomas Jefferson University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
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