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.
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: S L Vargas; W T Hughes; M E Santolaya; A V Ulloa; C A Ponce; C E Cabrera; F Cumsille; F Gigliotti Journal: Clin Infect Dis Date: 2001-03-09 Impact factor: 9.079
Authors: Kehmia Titanji; Angelo De Milito; Alberto Cagigi; Rigmor Thorstensson; Sven Grützmeier; Ann Atlas; Bo Hejdeman; Frank P Kroon; Lucia Lopalco; Anna Nilsson; Francesca Chiodi Journal: Blood Date: 2006-04-27 Impact factor: 22.113
Authors: Gerald S Bloomfield; Prateeti Khazanie; Alison Morris; Cristina Rabadán-Diehl; Laura A Benjamin; David Murdoch; Virginia S Radcliff; Eric J Velazquez; Charles Hicks Journal: J Acquir Immune Defic Syndr Date: 2014-09-01 Impact factor: 3.731
Authors: Angela Malaspina; Susan Moir; Susan M Orsega; Joshua Vasquez; Natalie J Miller; Eileen T Donoghue; Shyamasundaran Kottilil; Misrak Gezmu; Dean Follmann; Galina M Vodeiko; Roland A Levandowski; JoAnn M Mican; Anthony S Fauci Journal: J Infect Dis Date: 2005-03-24 Impact factor: 5.226
Authors: A Jalil; P Moja; C Lambert; M Perol; L Cotte; J M Livrozet; A Boibieux; J M Vergnon; F Lucht; R Tran; C Contini; C Genin Journal: Infect Immun Date: 2000-03 Impact factor: 3.441
Authors: Melanie Hart; Alan Steel; Sally A Clark; Graeme Moyle; Mark Nelson; Don C Henderson; Robert Wilson; Frances Gotch; Brian Gazzard; Peter Kelleher Journal: J Immunol Date: 2007-06-15 Impact factor: 5.422
Authors: Brenda L Tesini; Terry W Wright; Jane E Malone; Constantine G Haidaris; Martha Harber; Andrea J Sant; Jennifer L Nayak; Francis Gigliotti Journal: Infect Immun Date: 2017-03-23 Impact factor: 3.441