title: CpG-oligodeoxynucleotide is a potent adjuvant with an Entamoeba histolytica Gal-inhibitable lectin vaccine against amoebic liver abscess in gerbils.
abstract: The protozoan parasite Entamoeba histolytica causes invasive amoebiasis characterized by amoebic dysentery and liver abscesses (ALA). The E. histolytica galactose/N-acetyl-D-galactosamine-inhibitable lectin (Gal-lectin), an immunogenic surface molecule involved in colonization and invasion, is a promising vaccine candidate against amoebiasis. Gal-lectin is known to induce Th1 cytokines in macrophages and spleen cells in vitro, and a Th1 response is thought to be protective against ALA. In this study, we report the use of cytosine guanine oligodeoxynucleotide (CpG-ODN) as adjuvant to augment Th1 responses against Gal-lectin in the gerbil model of ALA. Gerbils were vaccinated intramuscularly with the native Gal-lectin plus CpG-ODN or a paired non-CpG control GpC-ODN, and control gerbils received CpG-ODN alone. One week after the last boost gerbils were challenged intrahepatically with 10(6) amoebae. Gerbils receiving CpG-ODN as adjuvant with Gal-lectin were completely protected against the development of ALA, whereas 50% of gerbils receiving GpC-ODN and Gal-lectin developed ALA and 85% of controls developed ALA. Stronger lymphoproliferation in response to the Gal-lectin and higher prechallenge titers of serum Gal-lectin-specific antibodies, capable of blocking amoebic adherence, were observed when CpG-ODN was used as adjuvant. Gerbils vaccinated with CpG-ODN and Gal-lectin also had significantly higher levels of gamma interferon, interleukin-12 (IL-12), and IL-2 mRNA than controls. These data indicate that CpG-ODN can enhance the Th1 responses, which improve the protective effects of Gal-lectin. This is the first report of the use of CpG as a potent Th1 adjuvant with Gal-lectin to increase protection against ALA formation.
authors.affiliation: Faculty of Medicine, Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Catherine P A
authors.initials: CP
authors.lastname: Ivory
authors.forename: Kathy
authors.initials: K
authors.lastname: Keller
authors.forename: Kris
authors.initials: K
authors.lastname: Chadee
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D018899:CpG Islands / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004748:Entamoeba histolytica / Q000276:immunology*; D037161:Galectins / Q000276:immunology*; D005849:Gerbillinae; D008101:Liver Abscess, Amebic / Q000276:immunology* / Q000517:prevention & control; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; C408982:CPG-oligonucleotide; D016207:Cytokines; D037161:Galectins; D009838:Oligodeoxyribonucleotides; D016052:Protozoan Vaccines; D012333:RNA, Messenger