Vaccine-Induced Immunogenicity and Protection Against Pneumocystis Pneumonia in a Nonhuman Primate Model of HIV and Pneumocystis Coinfection

J Infect Dis. 2016 May 15;213(10):1586-95. doi: 10.1093/infdis/jiw032. Epub 2016 Jan 27.


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.

Keywords: HIV/SIV; Pneumocystis; humoral immunity; macaque; nonhuman primate; vaccine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Fungal / biosynthesis
  • Antibodies, Fungal / blood
  • Coinfection
  • Disease Models, Animal
  • Female
  • Fungal Vaccines* / immunology
  • HIV Infections / complications
  • HIV Infections / immunology*
  • Humans
  • Immunocompromised Host
  • Immunologic Memory
  • Lung / immunology
  • Lung / microbiology
  • Macaca fascicularis
  • Macaca mulatta
  • Male
  • Pneumocystis carinii / immunology*
  • Pneumonia, Pneumocystis / complications
  • Pneumonia, Pneumocystis / immunology*
  • Pneumonia, Pneumocystis / prevention & control
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Pulmonary Disease, Chronic Obstructive / prevention & control
  • Random Allocation
  • Recombinant Proteins / immunology
  • Serine Endopeptidases / immunology*


  • Antibodies, Fungal
  • Fungal Vaccines
  • Recombinant Proteins
  • Kex1 protein, Pneumocystis jirovecii
  • Serine Endopeptidases