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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

Identification of Sm29 on skin-stage schistosomula tegument by Western blot.Two micrograms of purified skin-stage schistosomula tegument was applied onto 12% SDS-PAGE and transferred to a nitrocellulose membrane by western blot. After that, the membrane was probed with serum from rSm29 vaccinated mice or naïve animals diluted 1∶500 in TBST. Arrow indicates the native Sm29. The molecular mass markers, from top to bottom, are: 97, 66, 45, 30, 20.1, and 14.4 kDa.
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pntd-0000308-g002: Identification of Sm29 on skin-stage schistosomula tegument by Western blot.Two micrograms of purified skin-stage schistosomula tegument was applied onto 12% SDS-PAGE and transferred to a nitrocellulose membrane by western blot. After that, the membrane was probed with serum from rSm29 vaccinated mice or naïve animals diluted 1∶500 in TBST. Arrow indicates the native Sm29. The molecular mass markers, from top to bottom, are: 97, 66, 45, 30, 20.1, and 14.4 kDa.

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)

Identification of Sm29 on skin-stage schistosomula tegument by Western blot.Two micrograms of purified skin-stage schistosomula tegument was applied onto 12% SDS-PAGE and transferred to a nitrocellulose membrane by western blot. After that, the membrane was probed with serum from rSm29 vaccinated mice or naïve animals diluted 1∶500 in TBST. Arrow indicates the native Sm29. The molecular mass markers, from top to bottom, are: 97, 66, 45, 30, 20.1, and 14.4 kDa.
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0000308-g002: Identification of Sm29 on skin-stage schistosomula tegument by Western blot.Two micrograms of purified skin-stage schistosomula tegument was applied onto 12% SDS-PAGE and transferred to a nitrocellulose membrane by western blot. After that, the membrane was probed with serum from rSm29 vaccinated mice or naïve animals diluted 1∶500 in TBST. Arrow indicates the native Sm29. The molecular mass markers, from top to bottom, are: 97, 66, 45, 30, 20.1, and 14.4 kDa.
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