title: Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine?
abstract: BACKGROUND
  Rhesus macaques are unusual among schistosome hosts, self-curing from an established infection and thereafter manifesting solid immunity against a challenge, an ideal model for vaccine development. Previously, the immunological basis of self-cure was confirmed; surviving worms had ceased feeding but how immunological pressure achieved this was unclear. The schistosome esophagus is not simply a conduit for blood but plays a central role in its processing. Secretions from the anterior and posterior esophageal glands mix with incoming blood causing erythrocyte lysis and tethering and killing of leucocytes.
  
  
  RESULTS
  We have analysed the self-cure process in rhesus macaques infected with Schistosoma japonicum. Faecal egg output and circulating antigen levels were used to chart the establishment of a mature worm population and its subsequent demise. The physiological stress of surviving females at perfusion was especially evident from their pale, shrunken appearance, while changes in the structure and function of the esophagus were observed in both sexes. In the anterior region electron microscopy revealed that the vesicle secretory process was disrupted, the tips of lining corrugations being swollen by greatly enlarged vesicles and the putative sites of vesicle release obscured by intense deposits of IgG. The lumen of the posterior esophagus in starving worms was occluded by cellular debris and the lining cytoplasmic plates were closely adherent, also potentially preventing secretion. Seven proteins secreted by the posterior gland were identified and IgG responses were detected to some or all of them. Intrinsic rhesus IgG colocalized with secreted SjMEGs 4.1, 8.2, 9, 11 and VAL-7 on cryosections, suggesting they are potential targets for disruption of function.
  
  
  CONCLUSIONS
  Our data suggest that rhesus macaques self-cure by blocking esophagus function with antibody; the protein products of the glands provide a new class of potential vaccine targets.
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China; Key Laboratory of Parasitology and Vector Biology, Ministry of Health, Shanghai, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Li
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China; Key Laboratory of Parasitology and Vector Biology, Ministry of Health, Shanghai, China.
authors.forename: Yu-Xin
authors.initials: YX
authors.lastname: Xu
authors.affiliation: Centre for Immunology and Infection, Department of Biology, University of York, York, United Kingdom.
authors.forename: Gill
authors.initials: G
authors.lastname: Vance
authors.affiliation: Kunming Institute of Zoology, Chinese Academy of Science, Kunming, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Kunming Institute of Zoology, Chinese Academy of Science, Kunming, China.
authors.forename: Long-Bao
authors.initials: LB
authors.lastname: Lv
authors.affiliation: Department of Parasitology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Govert J
authors.initials: GJ
authors.lastname: van Dam
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China; Key Laboratory of Parasitology and Vector Biology, Ministry of Health, Shanghai, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Cao
authors.affiliation: Centre for Immunology and Infection, Department of Biology, University of York, York, United Kingdom.
authors.forename: R Alan
authors.initials: RA
authors.lastname: Wilson
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004947:Esophagus / Q000033:anatomy & histology / Q000502:physiology; D005260:Female; D008253:Macaca mulatta; D008297:Male; D018419:Primate Diseases / Q000276:immunology* / Q000469:parasitology; D012549:Schistosoma japonicum / Q000033:anatomy & histology / Q000502:physiology*; D012554:Schistosomiasis japonica / Q000276:immunology / Q000469:parasitology / Q000662:veterinary*; D014612:Vaccines / Q000276:immunology
chemical_list: D000909:Antibodies, Helminth; D014612:Vaccines