Pulmonary infection with the fungal pathogen, Pneumocystis jirovecii, is a common and often fatal complication of HIV infection. Emerging data suggest that Pneumocystis may also complicate lung diseases in non-HIV-infected hosts. The long-term goal of this Program Project is to develop a vaccine against Pneumocystis. To that end, we have identified a novel vaccine candidate for Pneumocysfis termed mini-kexin. We will identify mechanisms through which CD4+ T-lymphocytes participate in systemic and mucosal immune responses to the kexin vaccine. This project will test the experimental hypothesis that CD4+ T-lymphocyte help is necessary for optimal mucosal CD8+ T-cell and antibody responses to mini-kexin using a prime/boost vaccine strategy. The goal of these studies will be to define the role of CD4+ T-lymphocytes in vaccine responses in normal hosts. They are meant to complement experiments proposed for Project 2 that will focus on CD4-independent vaccine responses. In addition to mini-kexin, we will also investigate in our model systems antigen candidates identified through the Antigen Discovery Core. There are 4 Specific Aims: 1. To test the concept that CD4+ T-lymphocyte help is necessary during the priming phase of mini-kexin vaccination for optimal CD8+ and antibody responses in lung tissue. 2. To test the concept that T-lymphocyte CD40 ligand interactions are necessary for optimal CD8+ and antibody vaccine responses in lung tissue. 3. To test the concept that Stat3 and IL-17-secrefing T-lymphocytes are required for optimal CD8+ and antibody vaccine responses in lung tissue. 4. To validate the role of CD40+ and IL-17-secrefing T-lymphocytes in local vaccine responses of nonhuman primates.

Public Health Relevance

The results of these experiments may lead to novel approaches to augment mucosal immunity against Pneumocystis in both immunocompetent and HIV-infected individuals. Collaborative experiments will extend selected results of these experiments to vaccination against tuberculosis in Project 3.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL076100-10
Application #
8708934
Study Section
Special Emphasis Panel (ZHL1-PPG-A)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
10
Fiscal Year
2014
Total Cost
$337,127
Indirect Cost
$99,714
Name
Louisiana State Univ Hsc New Orleans
Department
Type
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
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