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.
| 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 |
| 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 |
| 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 |
| 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 |
| Naftolin, Frederick; Mehr, Holly; Fadiel, Ahmed (2016) Sex Steroids Block the Initiation of Atherosclerosis. Reprod Sci 23:1620-1625 |
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