Schistosoma mansoni tegument protein Sm29 is able to induce a Th1-type of immune response and protection against parasite infection

Cardoso, Fernanda C., Macedo, Gilson C., Gava, Elisandra, Kitten, Gregory T., Mati, Vitor L., de Melo, Alan L., Caliari, Marcelo V., Almeida, Giulliana T., Venancio, Thiago M., Verjovski-Almeida, Sergio and Oliveira, Sergio C. (2008) Schistosoma mansoni tegument protein Sm29 is able to induce a Th1-type of immune response and protection against parasite infection. PLoS Neglected Tropical Diseases, 2 10: e308.1-e308.10. doi:10.1371/journal.pntd.0000308

Author Cardoso, Fernanda C.
Macedo, Gilson C.
Gava, Elisandra
Kitten, Gregory T.
Mati, Vitor L.
de Melo, Alan L.
Caliari, Marcelo V.
Almeida, Giulliana T.
Venancio, Thiago M.
Verjovski-Almeida, Sergio
Oliveira, Sergio C.
Title Schistosoma mansoni tegument protein Sm29 is able to induce a Th1-type of immune response and protection against parasite infection
Formatted title
Schistosoma mansoni tegument protein Sm29 is able to induce a Th1-type of immune response and protection against parasite infection
Journal name PLoS Neglected Tropical Diseases   Check publisher's open access policy
ISSN 1935-2727
Publication date 2008-07
Sub-type Article (original research)
DOI 10.1371/journal.pntd.0000308
Open Access Status DOI
Volume 2
Issue 10
Start page e308.1
End page e308.10
Total pages 10
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted abstract
Background: Schistosomiasis continues to be a significant public health problem. This disease affects 200 million people worldwide and almost 800 million people are at risk of acquiring the infection. Although vaccine development against this disease has experienced more failures than successes, encouraging results have recently been obtained using membrane-spanning protein antigens from the tegument of Schistosoma mansoni. Our group recently identified Sm29, another antigen that is present at the adult worm tegument surface. In this study, we investigated murine cellular immune responses to recombinant (r) Sm29 and tested this protein as a vaccine candidate.

Methods and Findings: We first show that Sm29 is located on the surface of adult worms and lung-stage schistosomula through confocal microscopy. Next, immunization of mice with rSm29 engendered 51%, 60% and 50% reduction in adult worm burdens, in intestinal eggs and in liver granuloma counts, respectively (p<0.05). Protective immunity in mice was associated with high titers of specific anti-Sm29 IgG1 and IgG2a and elevated production of IFN-γ, TNF-α and IL-12, a typical Th1 response. Gene expression analysis of worms recovered from rSm29 vaccinated mice relative to worms from control mice revealed a significant (q<0.01) down-regulation of 495 genes and up-regulation of only 22 genes. Among down-regulated genes, many of them encode surface antigens and proteins associated with immune signals, suggesting that under immune attack schistosomes reduce the expression of critical surface proteins.

Conclusion: This study demonstrates that Sm29 surface protein is a new vaccine candidate against schistosomiasis and suggests that Sm29 vaccination associated with other protective critical surface antigens is the next logical strategy for improving protection.

Author Summary: Schistosomiasis is the most important human helminth infection in terms of morbidity and mortality. Although the efforts to develop a vaccine against this disease have experienced failures, a new generation of surface antigens revealed by proteomic studies changed this scenario. Our group has characterized the protein Sm29 described previously as one of the most exposed and expressed antigens in the outer tegument of Schistosoma mansoni. Studies in patients living in endemic areas for schistosomiasis revealed high levels of IgG1 and IgG3 anti-Sm29 in resistant individuals. In this study, confocal microscope analysis showed Sm29 present in the surface of lung-stage schistosoluma and adult worms. Recombinant Sm29, when used as vaccine candidate, induced high levels of protection in mice. This protection was associated with a typical Th1 immune response and reduction of worm burden, liver granulomas and in intestinal eggs. Further, microarray analysis of worms recovered from vaccinated mice showed significant down-regulation of several genes encoding previously characterized vaccine candidates and/or molecules exposed on the surface, suggesting an immune evasion strategy of schistosomes under immune attack. These results demonstrated that Sm29 as one of the important antigens with potential to compose a vaccine against schistosomiasis.
© 2008 Cardoso et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Article number e308.

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 78 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 98 times in Scopus Article | Citations
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Created: Tue, 22 Mar 2011, 12:16:34 EST by Susan Allen on behalf of Institute for Molecular Bioscience