title: Vaccine-Induced Immunogenicity and Protection Against Pneumocystis Pneumonia in a Nonhuman Primate Model of HIV and Pneumocystis Coinfection.
abstract: BACKGROUND
  The ubiquitous opportunistic pathogen Pneumocystis jirovecii causes pneumonia in immunocompromised individuals, including human immunodeficiency virus (HIV)-infected individuals, and pulmonary colonization with P. jirovecii is believed to be a cofactor in the development of chronic obstructive pulmonary disease. There is no vaccine for P. jirovecii; however, most adults are seropositive, indicating natural immune priming to this pathogen. We have shown that humoral response to a recombinant subunit of the P. jirovecii protease kexin (KEX1) correlates with protection from P. jirovecii colonization and pneumonia.
  
  
  METHODS
  Here we evaluated the immunogenicity and protective capacity of the recombinant KEX1 peptide vaccine in a preclinical, nonhuman primate model of HIV-induced immunosuppression and Pneumocystis coinfection.
  
  
  RESULTS
  Immunization with KEX1 induced a robust humoral response remained at protective levels despite chronic simian immunodeficiency virus/HIV-induced immunosuppression. KEX1-immunized macaques were protected from Pneumocystis pneumonia, compared with mock-immunized animals (P= .047), following immunosuppression and subsequent natural, airborne exposure to Pneumocystis
  
  
  CONCLUSIONS
  These data support the concept that stimulation of preexisting immunological memory to Pneumocystis with a recombinant KEX1 vaccine prior to immunosuppression induces durable memory responses and protection in the context of chronic, complex immunosuppression.
authors.affiliation: Department of Immunology, University of Pittsburgh, Pennsylvania.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Kling
authors.affiliation: Department of Immunology, University of Pittsburgh, Pennsylvania.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Norris
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000096:biosynthesis / Q000097:blood; D060085:Coinfection; D004195:Disease Models, Animal; D005260:Female; D005657:Fungal Vaccines / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D016867:Immunocompromised Host; D007156:Immunologic Memory; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D045363:Pneumocystis carinii / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000150:complications / Q000276:immunology* / Q000517:prevention & control; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000517:prevention & control; D011897:Random Allocation; D011994:Recombinant Proteins / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology*
chemical_list: D000908:Antibodies, Fungal; D005657:Fungal Vaccines; D011994:Recombinant Proteins; C470926:Kex1 protein, Pneumocystis jirovecii; D012697:Serine Endopeptidases
keywords: HIV/SIV; Pneumocystis; humoral immunity; macaque; nonhuman primate; vaccine
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