title: Efficacy of a Gal-lectin subunit vaccine against experimental Entamoeba histolytica infection and colitis in baboons (Papio sp.).
abstract: To determine the efficacy of a Gal-lectin based intranasal synthetic peptide vaccine, we developed a new experimental primate model of Entamoeba histolytica intestinal infection. Release of xenic E. histolytica trophozoites (5×10(6)) into the small bowel of baboons (Papio sp.) resulted in a rapid intestinal anti-amebic antibody response and a brief infection; however, release of trophozoites directly into the cecum (5 baboons) elicited a sustained E. histolytica infection, as determined by quantitative fecal PCR, and an ulcerative, inflammatory colitis observed on colonoscopy and histopathology. In three controlled experiments, baboons received four immunizations at seven day intervals of 1600 μg of the vaccine/nostril, with Cholera toxin, 20 μg/nostril as adjuvant; vaccinated (n=6) and control baboons (n=6) baboons were then challenged via colonoscopy with xenic trophozoites (5×10(6)). During 90 days of follow up, 250 of 415 (60.24%) fecal samples in control baboons had a (+) PCR for E. histolytica, compared to only 36 of 423 (8.51%) samples from vaccinated baboons (P<0.001). All 6 vaccinated baboons were free of infection by the 51st day after challenge, 5 of 6 controls positive had (+) fecal PCRs for up to 126 days post-challenge (P=0.019). Inflammatory colitis developed in 4 of 6 control baboons post-challenge, with invasive E. histolytica trophozoites present in 2 of the 4 on histopathology. There was no evidence of inflammatory colitis or parasite invasion in any of the vaccinated baboons; there was a strong inverse correlation between positive ELISA OD value indicating the presence of intestinal anti-peptide IgA antibodies and baboons having a positive fecal PCR CT value, P<0.001. In conclusion, we developed a novel primate model of E. histolytica intestinal infection and demonstrated that a Gal-lectin-based intranasal synthetic peptide vaccine was highly efficacious in preventing experimental E. histolytica infection and colitis in baboons.
authors.affiliation: Department of Medicine, Medical College of Wisconsin, United States. mabdalla@mcw.edu
authors.forename: Mohamed D
authors.initials: MD
authors.lastname: Abd Alla
authors.forename: Roman
authors.initials: R
authors.lastname: Wolf
authors.forename: Gary L
authors.initials: GL
authors.lastname: White
authors.forename: Stanley D
authors.initials: SD
authors.lastname: Kosanke
authors.forename: David
authors.initials: D
authors.lastname: Cary
authors.forename: Jaco J
authors.initials: JJ
authors.lastname: Verweij
authors.forename: Mie-Jie
authors.initials: MJ
authors.lastname: Zhang
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Ravdin
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D002772:Cholera Toxin / Q000008:administration & dosage; D004195:Disease Models, Animal; D004404:Dysentery, Amebic / Q000517:prevention & control*; D004748:Entamoeba histolytica / Q000276:immunology*; D004749:Entamoebiasis / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000469:parasitology; D037102:Lectins / Q000276:immunology*; D010215:Papio; D016133:Polymerase Chain Reaction; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D037102:Lectins; D016052:Protozoan Vaccines; D022223:Vaccines, Subunit; D002772:Cholera Toxin