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Schistosoma mansoni Tegument Protein Sm29 Is Able to Induce a Th1-Type of Immune Response and Protection against Parasite Infection

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, enc...

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Autores principales: 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.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2553283/
https://www.ncbi.nlm.nih.gov/pubmed/18827884
http://dx.doi.org/10.1371/journal.pntd.0000308
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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.
author_facet 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.
author_sort Cardoso, Fernanda C.
collection PubMed
description 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.
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spelling pubmed-25532832008-10-01 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 Oliveira, Sergio C. PLoS Negl Trop Dis Research Article 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. Public Library of Science 2008-10-01 /pmc/articles/PMC2553283/ /pubmed/18827884 http://dx.doi.org/10.1371/journal.pntd.0000308 Text en Cardoso et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
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.
Schistosoma mansoni Tegument Protein Sm29 Is Able to Induce a Th1-Type of Immune Response and Protection against Parasite Infection
title Schistosoma mansoni Tegument Protein Sm29 Is Able to Induce a Th1-Type of Immune Response and Protection against Parasite Infection
title_full Schistosoma mansoni Tegument Protein Sm29 Is Able to Induce a Th1-Type of Immune Response and Protection against Parasite Infection
title_fullStr Schistosoma mansoni Tegument Protein Sm29 Is Able to Induce a Th1-Type of Immune Response and Protection against Parasite Infection
title_full_unstemmed Schistosoma mansoni Tegument Protein Sm29 Is Able to Induce a Th1-Type of Immune Response and Protection against Parasite Infection
title_short Schistosoma mansoni Tegument Protein Sm29 Is Able to Induce a Th1-Type of Immune Response and Protection against Parasite Infection
title_sort schistosoma mansoni tegument protein sm29 is able to induce a th1-type of immune response and protection against parasite infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2553283/
https://www.ncbi.nlm.nih.gov/pubmed/18827884
http://dx.doi.org/10.1371/journal.pntd.0000308
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