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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

Immunolocalization of Sm29 antigen on male and female adult worm and lung-stage schistosomula of S. mansoni.Polyclonal anti-Sm29 antibodies, serum from mice that received Freund́s adjuvant as negative control, and Cy5-conjugated anti-mice IgG were used. Actin was visualized by falloidin-Alexa fluor 488. The parasites were fixed in Omnifix II and used to whole-mount or section immunolocalization. (A and B) Whole-mount immunolocalization of Sm29 antigen on the surface (outer tegument) of male adult worm and (C) lung-stage schistosomula of S. mansoni. (D) Immunolocalization of Sm29 on the surface (outer tegument) of male adult worm, and (E) on the surface (outer tegument) and in some internal tissues on the female adult worm using deparaffinized sections of the parasites. Localization of Sm29 is identified by the orange color and actin filaments by the green color.
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pntd-0000308-g001: Immunolocalization of Sm29 antigen on male and female adult worm and lung-stage schistosomula of S. mansoni.Polyclonal anti-Sm29 antibodies, serum from mice that received Freund́s adjuvant as negative control, and Cy5-conjugated anti-mice IgG were used. Actin was visualized by falloidin-Alexa fluor 488. The parasites were fixed in Omnifix II and used to whole-mount or section immunolocalization. (A and B) Whole-mount immunolocalization of Sm29 antigen on the surface (outer tegument) of male adult worm and (C) lung-stage schistosomula of S. mansoni. (D) Immunolocalization of Sm29 on the surface (outer tegument) of male adult worm, and (E) on the surface (outer tegument) and in some internal tissues on the female adult worm using deparaffinized sections of the parasites. Localization of Sm29 is identified by the orange color and actin filaments by the green color.

Mentions: In the present study, we demonstrated the localization of Sm29 in the male and female adult worms and also in the lung-stage schistosomula of S. mansoni using specific antibodies to rSm29 produced in E. coli. The native Sm29 was located exclusively on the surface of lung-stage schistosomula and male adult worms of S. mansoni (Fig. 1A, B, C, D, and Video S1). The female adult worm showed Sm29 located on the surface and also in internal tissues (Fig. 1E). Confocal microscopy analysis also revealed that Sm29 is not present in the cercariae stage of S. mansoni (Figure S1), as expected from the absence of mRNA coding for this antigen in cercariae cDNA library [8]. Additionally, we detected Sm29 in the purified tegument fraction of the skin-stage schistosomula by western blot analysis using specific antibodies to rSm29 (Fig. 2).


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)

Immunolocalization of Sm29 antigen on male and female adult worm and lung-stage schistosomula of S. mansoni.Polyclonal anti-Sm29 antibodies, serum from mice that received Freund́s adjuvant as negative control, and Cy5-conjugated anti-mice IgG were used. Actin was visualized by falloidin-Alexa fluor 488. The parasites were fixed in Omnifix II and used to whole-mount or section immunolocalization. (A and B) Whole-mount immunolocalization of Sm29 antigen on the surface (outer tegument) of male adult worm and (C) lung-stage schistosomula of S. mansoni. (D) Immunolocalization of Sm29 on the surface (outer tegument) of male adult worm, and (E) on the surface (outer tegument) and in some internal tissues on the female adult worm using deparaffinized sections of the parasites. Localization of Sm29 is identified by the orange color and actin filaments by the green color.
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0000308-g001: Immunolocalization of Sm29 antigen on male and female adult worm and lung-stage schistosomula of S. mansoni.Polyclonal anti-Sm29 antibodies, serum from mice that received Freund́s adjuvant as negative control, and Cy5-conjugated anti-mice IgG were used. Actin was visualized by falloidin-Alexa fluor 488. The parasites were fixed in Omnifix II and used to whole-mount or section immunolocalization. (A and B) Whole-mount immunolocalization of Sm29 antigen on the surface (outer tegument) of male adult worm and (C) lung-stage schistosomula of S. mansoni. (D) Immunolocalization of Sm29 on the surface (outer tegument) of male adult worm, and (E) on the surface (outer tegument) and in some internal tissues on the female adult worm using deparaffinized sections of the parasites. Localization of Sm29 is identified by the orange color and actin filaments by the green color.
Mentions: In the present study, we demonstrated the localization of Sm29 in the male and female adult worms and also in the lung-stage schistosomula of S. mansoni using specific antibodies to rSm29 produced in E. coli. The native Sm29 was located exclusively on the surface of lung-stage schistosomula and male adult worms of S. mansoni (Fig. 1A, B, C, D, and Video S1). The female adult worm showed Sm29 located on the surface and also in internal tissues (Fig. 1E). Confocal microscopy analysis also revealed that Sm29 is not present in the cercariae stage of S. mansoni (Figure S1), as expected from the absence of mRNA coding for this antigen in cercariae cDNA library [8]. Additionally, we detected Sm29 in the purified tegument fraction of the skin-stage schistosomula by western blot analysis using specific antibodies to rSm29 (Fig. 2).

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