Prevention of intestinal amebiasis by vaccination with the Entamoeba histolytica Gal/GalNac lectin.
Prevention of intestinal infection by Entamoeba histolytica would block both invasive disease and parasite transmission. The amebic Gal/GalNAc lectin mediates parasite adherence to the colonic surface and fecal anti-lectin IgA is associated with protection from intestinal reinfection in children. We tested if vaccination with the E. histolytica Gal/GalNAc lectin could prevent cecal infection in a C3H mouse model of amebic colitis. Two trials using native lectin purified from the parasite and two trials using a 64 kDa recombinant fragment ("LecA") were performed with a combined intranasal and intraperitoneal immunization regimen using cholera toxin and Freund's adjuvants, respectively. Two weeks after immunization mice were challenged intracecally with trophozoites, and 4-12 weeks after challenge mice were sacrificed for histopathologic evaluation of infection. Vaccination prevented intestinal infection with efficacies of 84 and 100% in the two native lectin trials and 91 and 34% in the two LecA trials. Mice with detectable pre-challenge fecal anti-lectin IgA responses were significantly more resistant to infection than mice without fecal anti-lectin IgA responses. These results show for the first time that immunization with the Gal/GalNAc lectin can prevent intestinal amebiasis in mice and suggest a protective role for fecal anti-lectin IgA in vivo.
Houpt
Eric
E
Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, 300 Lane Rd, PO Box 801340, MR4 Building Room 2115, Charlottesville, VA 22908, USA. erh6k@virginia.edu
Barroso
Lisa
L
Lockhart
Lauren
L
Wright
Rhonda
R
Cramer
Carole
C
Lyerly
David
D
Petri
William A
WA
D000281:Administration, Intranasal; D000562:Amebiasis / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D000818:Animals; D000913:Antibodies, Protozoan / Q000032:analysis; D000953:Antigens, Protozoan / Q000032:analysis; D016466:CHO Cells; D002432:Cecum / Q000473:pathology; D002448:Cell Adhesion; D006224:Cricetinae; D004748:Entamoeba histolytica / Q000276:immunology*; D005243:Feces / Q000737:chemistry / Q000469:parasitology; D005260:Female; D007070:Immunoglobulin A / Q000032:analysis / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D007422:Intestines / Q000469:parasitology; D037102:Lectins / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014611:Vaccination
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C434499:Igl1 protein, Entamoeba histolytica; D007070:Immunoglobulin A; D037102:Lectins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines