The goal of this project is to characterize cellular immune responses to HIV-1 in highly exposed, uninfected (EU) individuals. As a """"""""naturally vaccinated"""""""" population these patients have been shown to mount HIV-1 specific CTL responses. The overall goal of this proposal is to characterize potential protective immune responses that could be targeted in an HIV-1 vaccine. This proposal aims to study 1) The clonality and persistence of CTL in EU women. These studies may provide insight into the mechanisms driving induction and maintenance of CTL in EU individuals. 2) Characterize the lymphocyte population including antigen specificity and cytokine release from cervicovaginal samples of EU women.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI047746-03
Application #
6374542
Study Section
Special Emphasis Panel (ZRG1-VACC (03))
Program Officer
Ahlers, Jeffrey D
Project Start
2000-07-01
Project End
2003-06-30
Budget Start
2001-07-01
Budget End
2003-06-30
Support Year
3
Fiscal Year
2001
Total Cost
$267,000
Indirect Cost
Name
J. David Gladstone Institutes
Department
Type
DUNS #
047120084
City
San Francisco
State
CA
Country
United States
Zip Code
94158
Karlsson, R Karl; Jennes, Wim; Page-Shafer, Kimberly et al. (2004) Poorly soluble peptides can mimic authentic ELISPOT responses. J Immunol Methods 285:89-92
Shacklett, Barbara L; Cox, Catherine A; Sandberg, Johan K et al. (2003) Trafficking of human immunodeficiency virus type 1-specific CD8+ T cells to gut-associated lymphoid tissue during chronic infection. J Virol 77:5621-31
Jennes, Wim; Kestens, Luc; Nixon, Douglas F et al. (2002) Enhanced ELISPOT detection of antigen-specific T cell responses from cryopreserved specimens with addition of both IL-7 and IL-15--the Amplispot assay. J Immunol Methods 270:99-108
Shacklett, Barbara L; Ling, Binhua; Veazey, Ronald S et al. (2002) Boosting of SIV-specific T cell responses in rhesus macaques that resist repeated intravaginal challenge with SIVmac251. AIDS Res Hum Retroviruses 18:1081-8
Shacklett, Barbara L; Means, Robert E; Larsson, Marie et al. (2002) Dendritic cell amplification of HIV type 1-specific CD8+ T cell responses in exposed, seronegative heterosexual women. AIDS Res Hum Retroviruses 18:805-15
Larsson, Marie; Wilkens, David T; Fonteneau, Jean-Francois et al. (2002) Amplification of low-frequency antiviral CD8 T cell responses using autologous dendritic cells. AIDS 16:171-80