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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Special Emphasis Panel (ZHL1-PPG-A)
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Louisiana State Univ Hsc New Orleans
New Orleans
United States
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Zheng, Mingquan; Cai, Yang; Eddens, Taylor et al. (2014) Novel pneumocystis antigen discovery using fungal surface proteomics. Infect Immun 82:2417-23
Chakraborty, Sourav; Cai, Yang; Tarr, Matthew A (2014) In vitro oxidative footprinting provides insight into apolipoprotein B-100 structure in low-density lipoprotein. Proteomics 14:2614-22
D'Souza, Alain J; Desai, Shyamal D; Rudner, Xiaowen L et al. (2013) Suppression of the macrophage proteasome by ethanol impairs MHC class I antigen processing and presentation. PLoS One 8:e56890
Kelly, Michelle N; Zheng, Mingquan; Ruan, Sanbao et al. (2013) Memory CD4+ T cells are required for optimal NK cell effector functions against the opportunistic fungal pathogen Pneumocystis murina. J Immunol 190:285-95
Patil, Ujwal S; Qu, Haiou; Caruntu, Daniela et al. (2013) Labeling primary amine groups in peptides and proteins with N-hydroxysuccinimidyl ester modified Fe3O4@SiO2 nanoparticles containing cleavable disulfide-bond linkers. Bioconjug Chem 24:1562-9
Porretta, Elizabeth; Happel, Kyle I; Teng, Xu S et al. (2012) The impact of alcohol on BCG-induced immunity against Mycobacterium tuberculosis. Alcohol Clin Exp Res 36:310-7
Auten, Matthew W; Huang, Weitao; Dai, Guixiang et al. (2012) CD40 ligand enhances immunogenicity of vector-based vaccines in immunocompetent and CD4+ T cell deficient individuals. Vaccine 30:2768-77
Shi, Xin; Zhang, Ping; Sempowski, Gregory D et al. (2011) Thymopoietic and bone marrow response to murine Pneumocystis pneumonia. Infect Immun 79:2031-42
Siggins, Robert W; Melvan, John N; Welsh, David A et al. (2011) Alcohol suppresses the granulopoietic response to pulmonary Streptococcus pneumoniae infection with enhancement of STAT3 signaling. J Immunol 186:4306-13
Shi, Xin; LeCapitaine, Nicole J; Rudner, Xiaowen L et al. (2009) Lymphocyte apoptosis in murine Pneumocystis pneumonia. Respir Res 10:57

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