title: Use of an Sm-p80-based therapeutic vaccine to kill established adult schistosome parasites in chronically infected baboons.
abstract: No vaccines are available for human use for any parasitic infections, including the helminthic disease schistosomiasis. Sm-p80, the large subunit of Schistosoma mansoni calpain, is a leading antigen candidate for a schistosomiasis vaccine. Prophylactic and antifecundity efficacies of Sm-p80 have been tested using a variety of vaccine approaches in both rodent and nonhuman primate models. However, the therapeutic efficacy of a Sm-p80-based vaccine had not been determined. In this study, we evaluated the therapeutic efficacy of Sm-p80 by using 2 different strategies and 3 Sm-p80-based vaccine formulations in baboons. Vaccine formulations were able to decrease established adult worms by 10%-36%, reduce retention of eggs in tissues by 10%-57%, and decrease egg excretion in feces by 13%-33%, compared with control formulations. Marked differences were observed in B and T cell immune correlates between vaccinated and control animals. This is the first report of killing of established adult schistosome worms by a vaccine. In addition to distinct prophylactic efficacy of Sm-p80, this study adds to the evidence that Sm-p80 is a potentially important antigen with both substantial prophylactic and therapeutic efficacies. These data reinforce that Sm-p80 should be moved forward along the path toward human clinical trials.
authors.affiliation: Center for Tropical Medicine and Infectious Diseases Department of Immunology and Molecular Microbiology.
authors.forename: Souvik
authors.initials: S
authors.lastname: Karmakar
authors.affiliation: Center for Tropical Medicine and Infectious Diseases Department of Immunology and Molecular Microbiology.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Natural Sciences, School of Arts and Sciences, Peru State College, Nebraska.
authors.forename: Gul
authors.initials: G
authors.lastname: Ahmad
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana.
authors.forename: Workineh
authors.initials: W
authors.lastname: Torben
authors.affiliation: Center for Tropical Medicine and Infectious Diseases Department of Immunology and Molecular Microbiology.
authors.forename: Mayeen U
authors.initials: MU
authors.lastname: Alam
authors.affiliation: Center for Tropical Medicine and Infectious Diseases Department of Immunology and Molecular Microbiology.
authors.forename: Loc
authors.initials: L
authors.lastname: Le
authors.affiliation: Department of Cellular Biology, University of Georgia, Athens.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Damian
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City.
authors.forename: Roman F
authors.initials: RF
authors.lastname: Wolf
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City.
authors.forename: Gary L
authors.initials: GL
authors.lastname: White
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City.
authors.forename: David W
authors.initials: DW
authors.lastname: Carey
authors.affiliation: Infectious Disease Research Institute PAI Life Sciences, Seattle, Washington.
authors.forename: Darrick
authors.initials: D
authors.lastname: Carter
authors.affiliation: Infectious Disease Research Institute.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.affiliation: Center for Tropical Medicine and Infectious Diseases Department of Immunology and Molecular Microbiology Department of Internal Medicine Department of Pathology, Texas Tech University Health Sciences Center, Lubbock.
authors.forename: Afzal A
authors.initials: AA
authors.lastname: Siddiqui
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood / Q000276:immunology; D000947:Antigens, Helminth / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002154:Calpain / Q000276:immunology*; D004195:Disease Models, Animal; D005243:Feces / Q000469:parasitology; D005260:Female; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D010215:Papio / Q000469:parasitology*; D010270:Parasite Egg Count; D012550:Schistosoma mansoni / Q000187:drug effects; D012555:Schistosomiasis mansoni / Q000188:drug therapy*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014612:Vaccines / Q000276:immunology*
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D020381:Interleukin-17; D014612:Vaccines; D015847:Interleukin-4; D007371:Interferon-gamma; D002154:Calpain
keywords: Schistosoma mansoni; Schistosomiasis; Sm-p80; baboon; calpain; nonhuman primate; therapeutic vaccine