title: Schistosoma mansoni Infection of Mice, Rats and Humans Elicits a Strong Antibody Response to a Limited Number of Reduction-Sensitive Epitopes on Five Major Tegumental Membrane Proteins.
abstract: Schistosomiasis is a major disease of the developing world for which no vaccine has been successfully commercialized. While numerous Schistosoma mansoni worm antigens have been identified that elicit antibody responses during natural infections, little is known as to the identities of the schistosome antigens that are most prominently recognized by antibodies generated through natural infection. Non-reducing western blots probed with serum from schistosome-infected mice, rats and humans on total extracts of larval or adult schistosomes revealed that a small number of antigen bands predominate in all cases. Recognition of each of these major bands was lost when the blots were run under reducing condition. We expressed a rationally selected group of schistosome tegumental membrane antigens in insect host cells, and used the membrane extracts of these cells to unambiguously identify the major antigens recognized by S. mansoni infected mouse, rat and human serum. These results revealed that a limited number of dominant, reduction-sensitive conformational epitopes on five major tegumental surface membrane proteins: SmTsp2, Sm23, Sm29, SmLy6B and SmLy6F, are primary targets of mouse, rat and human S. mansoni infection sera antibodies. We conclude that, Schistosoma mansoni infection of both permissive (mouse) and non-permissive (rat) rodent models, as well as humans, elicit a dominant antibody response recognizing a limited number of conformational epitopes on the same five tegumental membrane proteins. Thus it appears that neither infecting schistosomula nor mature adult schistosomes are substantively impacted by the robust circulating anti-tegumental antibody response they elicit to these antigens. Importantly, our data suggest a need to re-evaluate host immune responses to many schistosome antigens and has important implications regarding schistosome immune evasion mechanisms and schistosomiasis vaccine development.
authors.affiliation: Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, United States of America.
authors.forename: Greice
authors.initials: G
authors.lastname: Krautz-Peterson
authors.affiliation: Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, United States of America.
authors.forename: Michelle
authors.initials: M
authors.lastname: Debatis
authors.affiliation: Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, United States of America.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Tremblay
authors.affiliation: Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Sergio C
authors.initials: SC
authors.lastname: Oliveira
authors.affiliation: Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, United States of America.
authors.forename: Akram A
authors.initials: AA
authors.lastname: Da'dara
authors.affiliation: Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, United States of America.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Skelly
authors.affiliation: Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, United States of America.
authors.forename: Charles B
authors.identifier: 0000-0001-9738-1361
authors.initials: CB
authors.lastname: Shoemaker
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology*; D000917:Antibody Formation; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D005260:Female; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D051379:Mice; D051381:Rats; D012550:Schistosoma mansoni / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000469:parasitology
chemical_list: D000909:Antibodies, Helminth; D000939:Epitopes; D015801:Helminth Proteins; D008565:Membrane Proteins