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 #
2P01HL076100-07A1
Application #
8213970
Study Section
Special Emphasis Panel (ZHL1-PPG-A (O2))
Program Officer
Peavy, Hannah H
Project Start
2003-12-01
Project End
2016-07-31
Budget Start
2011-09-19
Budget End
2012-07-31
Support Year
7
Fiscal Year
2011
Total Cost
$1,784,677
Indirect Cost
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
Samuelson, Derrick R; Burnham, Ellen L; Maffei, Vincent J et al. (2018) The respiratory tract microbial biogeography in alcohol use disorder. Am J Physiol Lung Cell Mol Physiol 314:L107-L117
Maffei, Vincent J; Kim, Sangkyu; Blanchard 4th, Eugene et al. (2017) Biological Aging and the Human Gut Microbiota. J Gerontol A Biol Sci Med Sci 72:1474-1482
Byerley, Lauri O; Samuelson, Derrick; Blanchard 4th, Eugene et al. (2017) Changes in the gut microbial communities following addition of walnuts to the diet. J Nutr Biochem 48:94-102
Samuelson, Derrick R; Shellito, Judd E; Maffei, Vincent J et al. (2017) Alcohol-associated intestinal dysbiosis impairs pulmonary host defense against Klebsiella pneumoniae. PLoS Pathog 13:e1006426
Goldsmith, Felicia; Guice, Justin; Page, Ryan et al. (2017) Obese ZDF rats fermented resistant starch with effects on gut microbiota but no reduction in abdominal fat. Mol Nutr Food Res 61:
Ruan, Sanbao; Cai, Yang; Ramsay, Alistair J et al. (2017) B cell and antibody responses in mice induced by a putative cell surface peptidase of Pneumocystis murina protect against experimental infection. Vaccine 35:672-679
Naftolin, Frederick; Mehr, Holly; Fadiel, Ahmed (2016) Sex Steroids Block the Initiation of Atherosclerosis. Reprod Sci 23:1620-1625
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
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
Lammi, Matthew R; Ghonim, Mohamed A; Pyakurel, Kusma et al. (2016) Treatment with intranasal iloprost reduces disease manifestations in a murine model of previously established COPD. Am J Physiol Lung Cell Mol Physiol 310:L630-8

Showing the most recent 10 out of 49 publications