title: Immunization with Pneumocystis Cross-Reactive Antigen 1 (Pca1) Protects Mice against Pneumocystis Pneumonia and Generates Antibody to Pneumocystis jirovecii.
abstract: Pneumocystispneumonia (PcP) is a life-threatening infection that affects immunocompromised individuals. Nearly half of all PcP cases occur in those prescribed effective chemoprophylaxis, suggesting that additional preventive methods are needed. To this end, we have identified a unique mousePneumocystissurface protein, designatedPneumocystiscross-reactive antigen 1 (Pca1), as a potential vaccine candidate. Mice were immunized with a recombinant fusion protein containing Pca1. Subsequently, CD4+T cells were depleted, and the mice were exposed toPneumocystis murinaPca1 immunization completely protected nearly all mice, similar to immunization with wholePneumocystisorganisms. In contrast, all immunized negative-control mice developed PcP. Unexpectedly, Pca1 immunization generated cross-reactive antibody that recognizedPneumocystis jiroveciiandPneumocystis cariniiPotential orthologs of Pca1 have been identified inP. jiroveciiSuch cross-reactivity is rare, and our findings suggest that Pca1 is a conserved antigen and potential vaccine target. The evaluation of Pca1-elicited antibodies in the prevention of PcP in humans deserves further investigation.
authors.affiliation: Department of Pediatrics, University of Rochester, Rochester, New York, USA.
authors.forename: Brenda L
authors.identifier: http://orcid.org/0000-0001-6051-0027
authors.initials: BL
authors.lastname: Tesini
authors.affiliation: Department of Pediatrics, University of Rochester, Rochester, New York, USA.|Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
authors.forename: Terry W
authors.initials: TW
authors.lastname: Wright
authors.affiliation: Department of Pediatrics, University of Rochester, Rochester, New York, USA.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Malone
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Haidaris
authors.affiliation: Department of Pediatrics, University of Rochester, Rochester, New York, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Harber
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Sant
authors.affiliation: Department of Pediatrics, University of Rochester, Rochester, New York, USA.|Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Nayak
authors.affiliation: Department of Pediatrics, University of Rochester, Rochester, New York, USA Francis_gigliotti@urmc.rochester.edu.|Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Gigliotti
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000946:Antigens, Fungal / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D005656:Fungal Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology; D007114:Immunization; D051379:Mice; D011010:Pneumocystis / Q000235:genetics / Q000276:immunology*; D045363:Pneumocystis carinii / Q000235:genetics / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000276:immunology* / Q000517:prevention & control
chemical_list: D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D005656:Fungal Proteins; D005657:Fungal Vaccines
keywords: PcP; Pneumocystis; antibody; immunization; pneumonia; vaccine