Schistosoma mansoni Stomatin like protein-2 is located in the tegument and induces partial protection against challenge infection

Farias, Leonardo P., Cardoso, Fernanda C., Miyasato, Patricia A., Montoya, Bogar O., Tararam, Cibele A., Roffato, Henrique K., Kawano, Toshie, Gazzinelli, Andrea, Correa-Oliveira, Rodrigo, Coulson, Patricia S., Wilson, R. Alan, Oliveira, Sérgio C. and Leite, Luciana C. C. (2010) Schistosoma mansoni Stomatin like protein-2 is located in the tegument and induces partial protection against challenge infection. PLoS Neglected Tropical Diseases, 4 2: e597-1-e597-13. doi:10.1371/journal.pntd.0000597


Author Farias, Leonardo P.
Cardoso, Fernanda C.
Miyasato, Patricia A.
Montoya, Bogar O.
Tararam, Cibele A.
Roffato, Henrique K.
Kawano, Toshie
Gazzinelli, Andrea
Correa-Oliveira, Rodrigo
Coulson, Patricia S.
Wilson, R. Alan
Oliveira, Sérgio C.
Leite, Luciana C. C.
Title Schistosoma mansoni Stomatin like protein-2 is located in the tegument and induces partial protection against challenge infection
Formatted title
Schistosoma mansoni Stomatin like protein-2 is located in the tegument and induces partial protection against challenge infection

Journal name PLoS Neglected Tropical Diseases   Check publisher's open access policy
ISSN 1935-2727
1935-2735
Publication date 2010-02-09
Sub-type Article (original research)
DOI 10.1371/journal.pntd.0000597
Open Access Status DOI
Volume 4
Issue 2
Start page e597-1
End page e597-13
Total pages 13
Editor Jeffrey M. Bethony
Peter Hotez
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2011
Language eng
Formatted 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.

Methodology/Principal Findings:
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-γ and TNF-α, while no IL-4 production was detected, suggesting a Th1-predominant immune response.

Conclusions/Significance:
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.

Author Summary:
Schistosomiasis is a parasitic disease causing serious chronic morbidity in tropical countries. Together with the publication of the transcriptome database, a series of new vaccine candidates were proposed based on their functional classification. However, the prediction of vaccine candidates from sequence information or even by proteomics or microarrays data is somewhat speculative and there remains the considerable task of functional analysis of each new gene/protein. In this study, we present the characterization of one of these molecules, a stomatin like protein 2 (SmStoLP-2). Sequence analysis predicts signals that could contribute to protein membrane association and mitochondrial targeting, which was confirmed by differential extractions of schistosome tegument membranes and mitochondria. Additionally, confocal microscope analysis showed SmStoLP-2 present in the tegument of 7-day-old schistosomula and adult worms. Studies in patients living in endemic areas for schistosomiasis revealed high levels of IgG1, IgG2, IgG3 and IgA anti-SmStoLP-2 antibodies in individuals resistant to reinfection. Recombinant SmStoLP-2 protein, when used as vaccine, induced significant levels of protection in mice. This reduction in worm burden was associated with a typical Th1-type immune response. These results indicate that SmStoLP-2 could be useful in association with other antigens for the composition of a vaccine against schistosomiasis.
Keyword Squamous-cell carcinoma
Touch receptor neurons
C-elegans
Immune-response
Recombinant protein
Palmitoylation site
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Institute for Molecular Bioscience - Publications
 
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Created: Tue, 22 Mar 2011, 11:19:11 EST by Susan Allen on behalf of Institute for Molecular Bioscience