title: Identification and immunological characterization of three potential vaccinogens against Cryptosporidium species.
abstract: Cryptosporidiosis is a ubiquitous infectious disease, caused by the protozoan parasites Cryptosporidium hominis and Cryptosporidium parvum, leading to acute, persistent, and chronic diarrhea with life-threatening consequences in immunocompromised individuals. In developing countries, cryptosporidiosis in early childhood has been associated with subsequent significant impairment in growth, physical fitness, and intellectual abilities. Currently, vaccines are unavailable and chemotherapeutics are toxic and impractical, and agents for immunoprophylaxis or treatment of cryptosporidiosis are a high priority. Availability of the genome sequences for C. hominis and C. parvum provides new opportunities to procure and examine novel vaccine candidates. Using the novel approach of "reverse vaccinology," we identified several new potential vaccine candidates. Three of these antigens--Cp15, profilin, and a Cryptosporidium apyrase--were delivered in heterologous prime-boost regimens as fusions with cytolysin A (ClyA) in a Salmonella live vaccine vector and as purified recombinant antigens, and they were found to induce specific and potent humoral and cellular immune responses, suggesting their potential as new vaccinogens against Cryptosporidium infection.
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23284-2030, USA.
authors.forename: Patricio A
authors.initials: PA
authors.lastname: Manque
authors.forename: Fernando
authors.initials: F
authors.lastname: Tenjo
authors.forename: Ute
authors.initials: U
authors.lastname: Woehlbier
authors.forename: Ana M
authors.initials: AM
authors.lastname: Lara
authors.forename: Myrna G
authors.initials: MG
authors.lastname: Serrano
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.forename: João M
authors.initials: JM
authors.lastname: Alves
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Smeltz
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Conrad
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Buck
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D016785:Cryptosporidium parvum / Q000235:genetics / Q000276:immunology*; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D007117:Immunization, Secondary / Q000379:methods; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012475:Salmonella / Q000235:genetics; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D004337:Drug Carriers; D016052:Protozoan Vaccines; D011993:Recombinant Fusion Proteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic