Evidence suggests that the length of clinical latency of HIV infection may be determined by the levels of persisting viral load and control of viremia is primarily effected by cytolytic T lymphocytes (CTL). Although individuals often mount vigorous CTL responses to HIV during the course of natural infection, the naturally induced CTL responses are usually not sufficient because infection eventually worsens and develops into AIDS. Therefore, boosting the initial CTL responses through vaccination is thought to be beneficial by reducing viral load low enough so that infected individuals become long-term asymptomatic. The goal of this project is to facilitate the development of a HIV vaccine that will elicit a strong and long-lasting CTL response by better understanding the nature of T cell memory and providing an easy and reliable assay for memory T cells. To this end we will construct a transgenic mouse strain in which responding T cells and surviving memory T cells are marked by the expression of an exogenous gene. Using the novel mouse model, we will systematically evaluate CTL responses and memory CTLs to protein and DNA vaccines of hsp70-SIV fusions and different vaccination protocols to identify the most effective vaccine candidate and vaccination strategy for further evaluation in primates and humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI044478-05
Application #
6511114
Study Section
Special Emphasis Panel (ZAI1-VSG-A)
Program Officer
Bridges, Sandra H
Project Start
1998-05-01
Project End
2003-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
5
Fiscal Year
2002
Total Cost
$324,036
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Internal Medicine/Medicine
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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Ge, Qing; Eisen, Herman N; Chen, Jianzhu (2004) Use of siRNAs to prevent and treat influenza virus infection. Virus Res 102:37-42
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Ge, Qing; Hu, Hui; Eisen, Herman N et al. (2002) Different contributions of thymopoiesis and homeostasis-driven proliferation to the reconstitution of naive and memory T cell compartments. Proc Natl Acad Sci U S A 99:2989-94
Ge, Qing; Stone, Jennifer D; Thompson, M Todd et al. (2002) Soluble peptide-MHC monomers cause activation of CD8+ T cells through transfer of the peptide to T cell MHC molecules. Proc Natl Acad Sci U S A 99:13729-34

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