title: Inconsistent protective efficacy and marked polymorphism limits the value of Schistosoma japonicum tetraspanin-2 as a vaccine target.
abstract: BACKGROUND
  Schistosoma mansoni tetraspanin 2 (Sm-TSP-2) has been shown to be strongly recognized by IgG1 and IgG3 antibodies from individuals putatively resistant to schistosome infection, but not chronically infected people, and to induce high levels of protection against challenge infection in the murine model of schistosomiasis. Amplification by PCR of homologous sequences from male and female S. japonicum worms showed the presence of 7 different clusters or subclasses of S. japonicum TSP-2. We determined the protective efficacy of one subclass - Sj-TSP-2e.
  
  
  RESULTS
  Following the alignment of 211 cDNAs, we identified 7 clusters encoding S. japonicum TSP-2 (Sj-TSP-2) based on sequence variation in the large extracellular loop (LEL) region with differing frequency of transcription in male and female worms. Quantitative PCR analysis revealed elevated expression of Sj-TSP-2 in adult worms compared with other life cycle stages. We expressed in E. coli the LEL region of one of the clusters which exhibited a high frequency of transcription in female worms, and showed the purified recombinant protein (Sj-TSP-2e) was recognised by 43.1% of sera obtained from confirmed schistosomiasis japonica patients. Vaccination of mice with the recombinant protein induced high levels of IgG1 and IgG2 antibodies, but no consistent protective efficacy against challenge infection was elicited in three independent trials.
  
  
  CONCLUSIONS
  The highly polymorphic nature of the Sj-TSP-2 gene at the transcriptional level may limit the value of Sj-TSP-2 as a target for future S. japonicum vaccine development.
authors.affiliation: Molecular Parasitology Laboratory, Australian Centre for International and Tropical Health and Nutrition, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: Wenbao
authors.initials: W
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Mary
authors.initials: M
authors.lastname: Duke
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Jones
authors.forename: Ling
authors.initials: L
authors.lastname: Kuang
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Blair
authors.forename: Yuesheng
authors.initials: Y
authors.lastname: Li
authors.forename: Donald P
authors.initials: DP
authors.lastname: McManus
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D000947:Antigens, Helminth / Q000235:genetics* / Q000276:immunology*; D016000:Cluster Analysis; D056738:Cross Protection; D005260:Female; D015801:Helminth Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011110:Polymorphism, Genetic; D012549:Schistosoma japonicum / Q000235:genetics / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods; D014612:Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D015801:Helminth Proteins; D007074:Immunoglobulin G; D014612:Vaccines