title: Characterization of a surface glycoprotein from Echinococcus multilocularis and its mucosal vaccine potential in dogs.
abstract: Alveolar echinococcosis is a refractory disease caused by the metacestode stage of Echinococcus multilocularis. The life cycle of this parasite is maintained primarily between foxes and many species of rodents; thus, dogs are thought to be a minor definitive host except in some endemic areas. However, dogs are highly susceptible to E. multilocularis infection. Because of the close contact between dogs and humans, infection of dogs with this parasite can be an important risk to human health. Therefore, new measures and tools to control and prevent parasite transmission required. Using 2-dimensional electrophoresis followed by western blot (2D-WB) analysis, a large glycoprotein component of protoscoleces was identified based on reactivity to intestinal IgA in dogs experimentally infected with E. multilocularis. This component, designated SRf1, was purified by gel filtration using a Superose 6 column. Glycosylation analysis and immunostaining revealed that SRf1 could be distinguished from Em2, a major mucin-type antigen of E. multilocularis. Dogs (n=6) were immunized intranasally with 500 µg of SRf1 with cholera toxin subunit B by using a spray syringe, and a booster was given orally using an enteric capsule containing 15 mg of the same antigen. As a result, dogs immunized with this antigen showed an 87.6% reduction in worm numbers compared to control dogs (n=5) who received only PBS administration. A weak serum antibody response was observed in SRf1-immunized dogs, but there was no correlation between antibody response and worm number. We demonstrated for the first time that mucosal immunization using SRf1, a glycoprotein component newly isolated from E. multilocularis protoscoleces, induced a protection response to E. multilocularis infection in dogs. Thus, our data indicated that mucosal immunization using surface antigens will be an important tool to facilitate the development of practical vaccines for definitive hosts.
authors.affiliation: Department of Infectious Diseases, Hokkaido Institute of Public Health, Sapporo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kouguchi
authors.forename: Jun
authors.initials: J
authors.lastname: Matsumoto
authors.forename: Ryo
authors.initials: R
authors.lastname: Nakao
authors.forename: Kimiaki
authors.initials: K
authors.lastname: Yamano
authors.forename: Yuzaburo
authors.initials: Y
authors.lastname: Oku
authors.forename: Kinpei
authors.initials: K
authors.lastname: Yagi
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D004283:Dog Diseases / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D004285:Dogs; D004443:Echinococcosis; D004444:Echinococcosis, Hepatic / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control / Q000662:veterinary*; D048210:Echinococcus multilocularis / Q000276:immunology*; D005260:Female; D007070:Immunoglobulin A / Q000276:immunology; D007421:Intestine, Small / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000302:isolation & purification; D014612:Vaccines / Q000276:immunology*
chemical_list: D000947:Antigens, Helminth; D007070:Immunoglobulin A; D008562:Membrane Glycoproteins; D014612:Vaccines
references.citation: Mol Biochem Parasitol. 1999 Jul 30;102(1):43-52
references.pmid: 10477175
references.citation: J Parasitol. 1983 Dec;69(6):1168-70
references.pmid: 6674466
references.citation: Annu Rev Microbiol. 1997;51:311-40
references.pmid: 9343353
references.citation: Infect Immun. 2003 Sep;71(9):5314-23
references.pmid: 12933879
references.citation: Trends Parasitol. 2008 Sep;24(9):419-24
references.pmid: 18678528
references.citation: Epidemiol Infect. 2001 Dec;127(3):577-87
references.pmid: 11811893
references.citation: Parasitology. 2003;127 Suppl:S159-72
references.pmid: 15027612
references.citation: PLoS Negl Trop Dis. 2010 Jun 22;4(6):e722
references.pmid: 20582310
references.citation: Trends Parasitol. 2009 Feb;25(2):57-8
references.pmid: 19084478
references.citation: Am J Physiol. 1990 Jan;258(1 Pt 1):G96-102
references.pmid: 2154122
references.citation: Int J Parasitol. 1975 Aug;5(4):395-9
references.pmid: 1140879
references.citation: PLoS Negl Trop Dis. 2008 Jan 16;2(1):e125
references.pmid: 18235847
references.citation: J Med Chem. 2012 Dec 13;55(23):10347-62
references.pmid: 23106358
references.citation: Parasite Immunol. 1990 Mar;12(2):163-74
references.pmid: 2181385
references.citation: Exp Parasitol. 2010 Feb;124(2):238-43
references.pmid: 19769968
references.citation: Int J Parasitol. 2005 Feb;35(2):163-70
references.pmid: 15710437
references.citation: Parasitology. 1986 Jun;92 ( Pt 3):599-620
references.pmid: 3737243
references.citation: Mol Biochem Parasitol. 2003 Jan;126(1):25-33
references.pmid: 12554081
references.citation: Res Vet Sci. 2003 Jun;74(3):191-202
references.pmid: 12726737
references.citation: Immunology. 1994 Mar;81(3):480-6
references.pmid: 8206520
references.citation: J Infect Dis. 2006 Oct 1;194(7):966-74
references.pmid: 16960785
references.citation: Infect Immun. 1982 Aug;37(2):687-94
references.pmid: 6889574
references.citation: Emerg Infect Dis. 2003 Oct;9(10):1266-72
references.pmid: 14609462
references.citation: Parasitol Res. 2005 Mar;95(5):339-45
references.pmid: 15719262
references.citation: Am J Physiol. 1981 Jan;240(1):G10-6
references.pmid: 7457607
references.citation: Protein J. 2005 Jan;24(1):57-64
references.pmid: 15756818
references.citation: Infect Immun. 1980 Feb;27(2):632-7
references.pmid: 7380543
references.citation: Vet Immunol Immunopathol. 1998 Sep 16;65(1):29-41
references.pmid: 9802574
references.citation: Vet Immunol Immunopathol. 2004 Dec 28;102(4):441-50
references.pmid: 15541797
references.citation: Exp Parasitol. 2011 May;128(1):50-6
references.pmid: 21300062
references.citation: Anal Chem. 2008 Feb 15;80(4):1094-101
references.pmid: 18205388
references.citation: J Biol Chem. 2002 Feb 22;277(8):5742-8
references.pmid: 11729180
references.citation: Biosci Biotechnol Biochem. 2007 Feb;71(2):575-8
references.pmid: 17284827
references.citation: Parasitol Int. 2006;55 Suppl:S247-52
references.pmid: 16387527
references.citation: J Dairy Sci. 2000 Mar;83(3):507-17
references.pmid: 10750109
references.citation: Immunology. 1962 Jul;5:496-503
references.pmid: 13947115
references.citation: Vet Parasitol. 2005 Jan 4;127(1):43-49
references.pmid: 15619374