title: Schistosoma mansoni Stomatin like protein-2 is located in the tegument and induces partial protection against challenge infection.
abstract: BACKGROUND
  Schistosomiasis affects more than 200 million individuals worldwide, with a further 650 million living at risk of infection, constituting a severe health problem in developing countries. Even though an effective treatment exists, it does not prevent re-infection, and the development of an effective vaccine still remains the most desirable means of control for this disease.
  
  
  RESULTS
  Herein, we report the cloning and characterization of a S. mansoni Stomatin-like protein 2 (SmStoLP-2). In silico analysis predicts three putative sites for palmitoylation (Cys11, Cys61 and Cys330), which could contribute to protein membrane association; and a putative mitochondrial targeting sequence, similar to that described for human Stomatin-like protein 2 (HuSLP-2). The protein was detected by Western blot with comparable levels in all stages across the parasite life cycle. Fractionation by differential centrifugation of schistosome tegument suggested that SmStoLP-2 displays a dual targeting to the tegument membranes and mitochondria; additionally, immunolocalization experiments confirm its localization in the tegument of the adult worms and, more importantly, in 7-day-old schistosomula. Analysis of the antibody isotype profile to rSmStoLP-2 in the sera of patients living in endemic areas for schistosomiasis revealed that IgG1, IgG2, IgG3 and IgA antibodies were predominant in sera of individuals resistant to reinfection as compared to those susceptible. Next, immunization of mice with rSmStoLP-2 engendered a 30%-32% reduction in adult worm burden. Protective immunity in mice was associated with specific anti-rSmStoLP-2 IgG1 and IgG2a antibodies and elevated production of IFN-gamma and TNF-alpha, while no IL-4 production was detected, suggesting a Th1-predominant immune response.
  
  
  CONCLUSIONS
  Data presented here demonstrate that SmStoLP-2 is a novel tegument protein located in the host-parasite interface. It is recognized by different subclasses of antibodies in patients resistant and susceptible to reinfection and, based on the data from murine studies, shows protective potential against schistosomiasis. These results indicate that SmStoLP-2 could be useful in a combination vaccine.
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: Leonardo P
authors.initials: LP
authors.lastname: Farias
authors.forename: Fernanda C
authors.initials: FC
authors.lastname: Cardoso
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Miyasato
authors.forename: Bogar O
authors.initials: BO
authors.lastname: Montoya
authors.forename: Cibele A
authors.initials: CA
authors.lastname: Tararam
authors.forename: Henrique K
authors.initials: HK
authors.lastname: Roffato
authors.forename: Toshie
authors.initials: T
authors.lastname: Kawano
authors.forename: Andrea
authors.initials: A
authors.lastname: Gazzinelli
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Correa-Oliveira
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Coulson
authors.forename: R Alan
authors.initials: RA
authors.lastname: Wilson
authors.forename: Sérgio C
authors.initials: SC
authors.lastname: Oliveira
authors.forename: Luciana C C
authors.initials: LC
authors.lastname: Leite
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D000947:Antigens, Helminth / Q000032:analysis* / Q000235:genetics / Q000276:immunology*; D003001:Cloning, Molecular; D005260:Female; D015801:Helminth Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015388:Organelles / Q000737:chemistry; D012550:Schistosoma mansoni / Q000737:chemistry* / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000517:prevention & control*; D017422:Sequence Analysis, DNA; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014611:Vaccination
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D015801:Helminth Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma