title: Immunization with the Entamoeba histolytica surface metalloprotease EhMSP-1 protects hamsters from amebic liver abscess.
abstract: Diarrhea and amebic liver abscesses due to invasive Entamoeba histolytica infections are an important cause of morbidity and mortality in the developing world. Entamoeba histolytica adherence and cell migration, two phenotypes linked to virulence, are both aberrant in trophozoites deficient in the metallosurface protease EhMSP-1, which is a homologue of the Leishmania vaccine candidate leishmanolysin (GP63). We examined the potential of EhMSP-1 for use as a vaccine antigen to protect against amebic liver abscesses. First, existing serum samples from South Africans naturally infected with E. histolytica were examined by enzyme-linked immunosorbent assay (ELISA) for the presence of EhMSP-1-specific IgG. Nine of 12 (75%) people with anti-E. histolytica IgG also had EhMSP-1-specific IgG antibodies. We next used a hamster model of amebic liver abscess to determine the effect of immunization with a mixture of four recombinant EhMSP-1 protein fragments. EhMSP-1 immunization stimulated a robust IgG antibody response. Furthermore, EhMSP-1 immunization of hamsters reduced development of severe amebic liver abscesses following intrahepatic injection of E. histolytica by a combined rate of 68% in two independent animal experiments. Purified IgG from immunized compared to control animals bound to the surface of E. histolytica trophozoites and accelerated amebic lysis via activation of the classical complement cascade. We concluded that EhMSP-1 is a promising antigen that warrants further study to determine its full potential as a target for therapy and/or prevention of invasive amebiasis.
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Eduardo C
authors.initials: EC
authors.lastname: Roncolato
authors.affiliation: Department of Medicine, University of Vermont, Burlington, Vermont, USA.
authors.forename: José E
authors.initials: JE
authors.lastname: Teixeira
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: José E
authors.initials: JE
authors.lastname: Barbosa
authors.affiliation: Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Leandra N
authors.initials: LN
authors.lastname: Zambelli Ramalho
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA Department of Medicine, University of Vermont, Burlington, Vermont, USA christopher.huston@uvm.edu.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Huston
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000276:immunology; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology*; D017209:Apoptosis; D002448:Cell Adhesion; D002465:Cell Movement; D006224:Cricetinae; D004748:Entamoeba histolytica / Q000276:immunology*; D004749:Entamoebiasis / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008101:Liver Abscess, Amebic / Q000517:prevention & control*; D045726:Metalloproteases / Q000008:administration & dosage / Q000276:immunology*; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014611:Vaccination
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D045726:Metalloproteases