Recent studies have suggested that HIV-1 Tat should be considered as an important component of potential HIV vaccines. We propose investigating whether orally administered Tat can elicit systemic anti-Tat immune responses. We will express HIV-1 Tat in spinach. Following oral administration to mice, we will analyze systemic and mucosal humoral and cell-mediated reactivity to Tat. As suggested by preliminary data, and because of its ability to be taken up by cells and to bind to cell surface receptors, it is possible that native Tat could compromise the development of antiviral immunity. We therefore will analyze several Tat mutants that lack transactivating ability or the ability to be taken up by cells and determine whether they elicit a stronger immune response than wild type Tat. We will also determine whether either formulation improves the response to subsequent vaccination to a Tat-gpl20 DNA vaccine. These studies will provide important information on whether native or modified Tat should be included in an HIV vaccine and will provide data on the feasibility of oral administration of HIV antigens in edible plants.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI052763-01
Application #
6553920
Study Section
Special Emphasis Panel (ZRG1-VACC (03))
Program Officer
Bradac, James A
Project Start
2002-09-15
Project End
2004-08-31
Budget Start
2002-09-15
Budget End
2003-08-31
Support Year
1
Fiscal Year
2002
Total Cost
$207,000
Indirect Cost
Name
Thomas Jefferson University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Karasev, Alexander V; Foulke, Scott; Wellens, Candice et al. (2005) Plant based HIV-1 vaccine candidate: Tat protein produced in spinach. Vaccine 23:1875-80