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.
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.
|Goldsmith, Felicia; Guice, Justin; Page, Ryan et al. (2016) Obese ZDF rats fermented resistant starch with effects on gut microbiota but no reduction in abdominal fat. Mol Nutr Food Res :|
|Samuelson, Derrick R; de la Rua, Nicholas M; Charles, Tysheena P et al. (2016) Oral Immunization of Mice with Live Pneumocystis murina Protects against Pneumocystis Pneumonia. J Immunol 196:2655-65|
|Dai, Guixiang; Rady, Hamada F; Huang, Weitao et al. (2016) Gene-based neonatal immune priming potentiates a mucosal adenoviral vaccine encoding mycobacterial Ag85B. Vaccine 34:6267-6275|
|Charles, Tysheena P; Shellito, Judd E (2016) Human Immunodeficiency Virus Infection and Host Defense in the Lungs. Semin Respir Crit Care Med 37:147-56|
|Rady, Hamada F; Dai, Guixiang; Huang, Weitao et al. (2016) Flagellin Encoded in Gene-Based Vector Vaccines Is a Route-Dependent Immune Adjuvant. PLoS One 11:e0148701|
|Kling, Heather M; Norris, Karen A (2016) Vaccine-Induced Immunogenicity and Protection Against Pneumocystis Pneumonia in a Nonhuman Primate Model of HIV and Pneumocystis Coinfection. J Infect Dis 213:1586-95|
|Ruan, S; Samuelson, D R; Assouline, B et al. (2016) Treatment with Interleukin-7 Restores Host Defense against Pneumocystis in CD4+ T-Lymphocyte-Depleted Mice. Infect Immun 84:108-19|
|de la Rua, Nicholas M; Samuelson, Derrick R; Charles, Tysheena P et al. (2016) CD4(+) T-Cell-Independent Secondary Immune Responses to Pneumocystis Pneumonia. Front Immunol 7:178|
|Bruce-Keller, Annadora J; Salbaum, J Michael; Luo, Meng et al. (2016) Reply to: High-Fat Diet-Induced Dysbiosis as a Cause of Neuroinflammation. Biol Psychiatry 80:e5-6|
|Jolley, Sarah E; Alkhafaf, Qasim; Hough, Catherine et al. (2016) Presence of an Alcohol Use Disorder is Associated with Greater Pneumonia Severity in Hospitalized HIV-Infected Patients. Lung 194:755-62|
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