title: Oral Immunization of Mice with Live Pneumocystis murina Protects against Pneumocystis Pneumonia.
abstract: Pneumocystis pneumonia is a major cause of morbidity and mortality in immunocompromised patients, particularly those infected with HIV. In this study, we evaluated the potential of oral immunization with live Pneumocystis to elicit protection against respiratory infection with Pneumocystis murina. C57BL/6 mice vaccinated with live P. murina using a prime-boost vaccination strategy were protected from a subsequent lung challenge with P. murina at 2, 7, 14, and 28 d postinfection even after CD4(+) T cell depletion. Specifically, vaccinated immunocompetent mice had significantly faster clearance than unvaccinated immunocompetent mice and unvaccinated CD4-depleted mice remained persistently infected with P. murina. Vaccination also increased numbers of CD4(+) T cells, CD8(+) T cells, CD19(+) B cells, and CD11b(+) macrophages in the lungs following respiratory infection. In addition, levels of lung, serum, and fecal P. murina-specific IgG and IgA were increased in vaccinated animals. Furthermore, administration of serum from vaccinated mice significantly reduced Pneumocystis lung burden in infected animals compared with control serum. We also found that the diversity of the intestinal microbial community was altered by oral immunization with P. murina. To our knowledge, our data demonstrate for the first time that an oral vaccination strategy prevents Pneumocystis infection.
authors: Section of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112;
authors: Derrick R
authors: http://orcid.org/0000-0002-5356-1413
authors: DR
authors: Samuelson
authors: Section of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112;
authors: Nicholas M
authors: NM
authors: de la Rua
authors: Section of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112;
authors: Tysheena P
authors: TP
authors: Charles
authors: Section of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112;
authors: Sanbao
authors: S
authors: Ruan
authors: Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112; and.
authors: Christopher M
authors: http://orcid.org/0000-0002-7983-5275
authors: CM
authors: Taylor
authors: Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112; and.
authors: Eugene E
authors: EE
authors: Blanchard
authors: Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112; and.
authors: Meng
authors: http://orcid.org/0000-0001-8626-6456
authors: M
authors: Luo
authors: Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112; and Louisiana Vaccine Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112.
authors: Alistair J
authors: http://orcid.org/0000-0002-3506-4544
authors: AJ
authors: Ramsay
authors: Section of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112; Louisiana Vaccine Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112.
authors: Judd E
authors: http://orcid.org/0000-0001-7729-2708
authors: JE
authors: Shellito
authors: Section of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112; dwelsh@lsuhsc.edu.
authors: David A
authors: http://orcid.org/0000-0002-0008-6161
authors: DA
authors: Welsh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000908:Antibodies, Fungal / Q000378:metabolism; D005260:Female; D005657:Fungal Vaccines / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011010:Pneumocystis / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000276:immunology* / Q000517:prevention & control
chemical_list: D000908:Antibodies, Fungal; D005657:Fungal Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G