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

Cardoso FC, Macedo GC, Gava E, Kitten GT, Mati VL, de Melo AL, Caliari MV, Almeida GT, Venancio TM, Verjovski-Almeida S, Oliveira SC - PLoS Negl Trop Dis (2008)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

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-gamma, TNF-alpha 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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Related in: MedlinePlus

Sm29 induces IL-12 and TNF-α production by macrophages from TLR4 knockout mice.Levels of IL-12 (p40) (A) or TNF-α (B) were measured in the supernatants of inflammatory macrophages from TLR4 KO or wild-type mice stimulated for 24 hrs with rSm29 (25 μg/ml), E. coli LPS (1 μg/ml) or medium alone. Significant differences from stimulated TLR4 KO or C57BL/6 macrophages in relation to non-stimulated cells are denoted by an asterisk (*) for p<0.05.
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pntd-0000308-g004: Sm29 induces IL-12 and TNF-α production by macrophages from TLR4 knockout mice.Levels of IL-12 (p40) (A) or TNF-α (B) were measured in the supernatants of inflammatory macrophages from TLR4 KO or wild-type mice stimulated for 24 hrs with rSm29 (25 μg/ml), E. coli LPS (1 μg/ml) or medium alone. Significant differences from stimulated TLR4 KO or C57BL/6 macrophages in relation to non-stimulated cells are denoted by an asterisk (*) for p<0.05.

Mentions: Mice vaccinated with rSm29 showed elevated production of IFN-γ, TNF-α and IL-10 and absence of IL-4 (Table 2). Cultures used for measuring the cytokines were treated with polymyxin B to avoid non-specific stimulation due to eventual LPS contamination in the purified recombinant protein [17]. Additionally, rSm29 has stimulated peritoneal macrophages from C57BL/6 (2016±423 pg/ml) or TLR4 KO (1108±197 pg/ml) mice to produce IL-12 (Fig. 4). It is worth to emphasize that rSm29 has activated macrophages to secrete IL-12 which drives Th1 cell development. Protective immunity in mice against S. mansoni infection, before the onset of egg production, is thought to be the result of a Th1 pattern of immune response [23].


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

Cardoso FC, Macedo GC, Gava E, Kitten GT, Mati VL, de Melo AL, Caliari MV, Almeida GT, Venancio TM, Verjovski-Almeida S, Oliveira SC - PLoS Negl Trop Dis (2008)

Sm29 induces IL-12 and TNF-α production by macrophages from TLR4 knockout mice.Levels of IL-12 (p40) (A) or TNF-α (B) were measured in the supernatants of inflammatory macrophages from TLR4 KO or wild-type mice stimulated for 24 hrs with rSm29 (25 μg/ml), E. coli LPS (1 μg/ml) or medium alone. Significant differences from stimulated TLR4 KO or C57BL/6 macrophages in relation to non-stimulated cells are denoted by an asterisk (*) for p<0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2553283&req=5

pntd-0000308-g004: Sm29 induces IL-12 and TNF-α production by macrophages from TLR4 knockout mice.Levels of IL-12 (p40) (A) or TNF-α (B) were measured in the supernatants of inflammatory macrophages from TLR4 KO or wild-type mice stimulated for 24 hrs with rSm29 (25 μg/ml), E. coli LPS (1 μg/ml) or medium alone. Significant differences from stimulated TLR4 KO or C57BL/6 macrophages in relation to non-stimulated cells are denoted by an asterisk (*) for p<0.05.
Mentions: Mice vaccinated with rSm29 showed elevated production of IFN-γ, TNF-α and IL-10 and absence of IL-4 (Table 2). Cultures used for measuring the cytokines were treated with polymyxin B to avoid non-specific stimulation due to eventual LPS contamination in the purified recombinant protein [17]. Additionally, rSm29 has stimulated peritoneal macrophages from C57BL/6 (2016±423 pg/ml) or TLR4 KO (1108±197 pg/ml) mice to produce IL-12 (Fig. 4). It is worth to emphasize that rSm29 has activated macrophages to secrete IL-12 which drives Th1 cell development. Protective immunity in mice against S. mansoni infection, before the onset of egg production, is thought to be the result of a Th1 pattern of immune response [23].

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

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-gamma, TNF-alpha 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.

Show MeSH
Related in: MedlinePlus