In this renewal/resubmission, this Program Project will continue to develop novel vaccine candidates and vaccination for HIV-related pulmonary pathogens. A concern of the prior submission was a lack of synergy between projects focused on Pneumocystis jirovecii (P. murina in mice) and Mycobacterium tuberculosis as the immunological mechanism needed to control these HIV-associated pathogens are very disparate. Vaccine induced protection against PCP relies largely on antibody responses whereas TB requires T-cells responses. To achieve greater focus and synergy on a significant, persistent pulmonary pathogen, we have chosen to focus this resubmission application solely on the fungal pathogen, Pneumocystis jirovecii (P. murina in mice). Although the lungs contain resident phagocytes with some activity against microbial pathogens, efficient host defense requires the capacity to rapidly expand the numbers and functions of immune effector cells in lung tissue in response to an infectious challenge. The lungs mount a cellular response to such a challenge mainly by delivering new cells to lung tissue from other cellular compartments (bone marrow, lymphoid tissue) through the vasculature. The overall theme of this Program Proiect is to develop vaccination approaches to enhance the delivery of immune effector cells into lung tissue in order to prevent colonization or augment clearance of Pneumocystis. We believe that efficient vaccines for respiratory pathogens must stimulate both cellular and antibody responses at the site of host exposure to the pathogen- at mucosal surfaces in lung tissue. Furthermore, to adequately address the global problem of respiratory infection associated with HIV infection, candidate vaccines should have efficacy both in normal hosts and in persons with diminished numbers or function of T-lymphocytes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL076100-10
Application #
8708933
Study Section
Special Emphasis Panel (ZHL1-PPG-A (O2))
Program Officer
Caler, Elisabet V
Project Start
2003-12-01
Project End
2016-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
10
Fiscal Year
2014
Total Cost
$1,720,806
Indirect Cost
$255,852
Name
Louisiana State Univ Hsc New Orleans
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
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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