We propose to develop non-infectious virion-like particles (VLPs) of HIV-1 that can be used as a vaccination tool for the induction of a broad anti-viral immune response directed against all the major viral accessory proteins of HIV-1. Inactivated virion particles act as immunogens that can be utilized to induce therapeutic immunity. However, wild type virions of HIV-1 cannot be used to mount an immune response against HIV-1 accessory proteins, as they are either absent or present only in trace amounts in the particles. To overcome this limitation, particles will be engineered to contain high amounts of accessory proteins of HIV-1. To this end, HIV-1 Gag which is alone sufficient to drive the formation of virion particles will be fused at its C-terminus to the three early viral gene products Tat, Rev and Nef in a single fusion polyprotein. Four other viral proteins, Vpr, Vif, Vpu and Pol will be incorporated in trans into virion particles, using the ability of Vpr and of Vpr-fusion proteins to bind Gag and to be incorporated in high amounts into particles. This strategy will result in the production of non-infectious virion-like particles (VLPs) containing high amounts of Gag with all the major accessory proteins of HIV. To prove that modified VLPs can induce cellular immune responses directed against structural and accessory proteins of HIV-1 alike; VLPs will be used onto dendritic cells for presentation of VLP-derived epitopes to helper and cytotoxic T cells ex vivo. If the project is successfully completed, modified VLPs could be used alone or in combination with other strategies for vaccination against HIV-1.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI057092-01A2
Application #
6878914
Study Section
Special Emphasis Panel (ZRG1-VACC (01))
Program Officer
Li, Yen
Project Start
2005-02-01
Project End
2007-01-31
Budget Start
2005-02-01
Budget End
2006-01-31
Support Year
1
Fiscal Year
2005
Total Cost
$153,000
Indirect Cost
Name
Nat'L Institute of Health/Med Research Inserm-Paris
Department
Type
DUNS #
381614494
City
Paris
State
Country
France
Zip Code
75013