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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

Transcript level changes in selected genes of S. mansoni worms recovered from mice vaccinated with rSm29.The figure shows real-time RT-PCR validation experiment for six genes down-regulated in S. mansoni worms recovered from rSm29+adjuvant immunized mice (black bars) compared to worms from PBS+adjuvant injected control mice (white bars). The selected genes were: CD36-CD36-like class B scavenger receptor [S. mansoni]; Sm23-Sm23 kDa integral membrane protein [S. mansoni]; Sm14-Fatty acid-binding protein Sm14 [S. mansoni]; Superox-Superoxide dismutase [S. mansoni]; TGF-β RIP-TGF-β receptor interacting protein 1 [C. sinensis]; B-cell RAP-B-cell receptor-associated protein-like protein [S. mansoni]. Statistically significant differences of vaccinated mice compared to PBS+adjuvant control group is denoted by one asterisk (p<0.03).
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pntd-0000308-g005: Transcript level changes in selected genes of S. mansoni worms recovered from mice vaccinated with rSm29.The figure shows real-time RT-PCR validation experiment for six genes down-regulated in S. mansoni worms recovered from rSm29+adjuvant immunized mice (black bars) compared to worms from PBS+adjuvant injected control mice (white bars). The selected genes were: CD36-CD36-like class B scavenger receptor [S. mansoni]; Sm23-Sm23 kDa integral membrane protein [S. mansoni]; Sm14-Fatty acid-binding protein Sm14 [S. mansoni]; Superox-Superoxide dismutase [S. mansoni]; TGF-β RIP-TGF-β receptor interacting protein 1 [C. sinensis]; B-cell RAP-B-cell receptor-associated protein-like protein [S. mansoni]. Statistically significant differences of vaccinated mice compared to PBS+adjuvant control group is denoted by one asterisk (p<0.03).

Mentions: In order to investigate the impact of rSm29 vaccination on S. mansoni, worms that were recovered from vaccinated mice had their gene expression profile analyzed using microarrays. This analysis revealed significant (q<0.01) regulation of 517 genes (Table S1) in worms recovered from mice vaccinated with adjuvanted rSm29 when compared to control mice injected with adjuvanted phosphate-buffered saline; of these, 495 genes (96%) were down-regulated and only 22 genes (4%) were up-regulated. Among down-regulated genes, several of them caught our attention and they fell into four major categories: tegument proteins (Sm23 and CD36-like class B scavenger receptor), membrane proteins (tetraspanin TE736), lipid metabolism (Sm14), receptor interacting proteins (B-cell receptor-associated protein and TGF-beta receptor interacting protein) and others (superoxide dismutase and Sm65) (Table 3). To validate the microarray data, we selected six genes (Sm23, Sm14, superoxide dismutase, CD36-like class B scavenger receptor, B-cell receptor-associated protein and TGF-β receptor interacting protein) and performed real-time RT-PCR. As demonstrated in Figure 5, real-time RT-PCR of all six tested genes confirmed the reduced expression previously determined by microarray analysis. Based on the data shown in Table 3 and Figure 5, we hypothesize that in rSm29 protected mice a reduced expression of these critical surface antigens enables the parasites to adapt to the host in the face of an ongoing antiparasite immune response developed in vaccinated animals.


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)

Transcript level changes in selected genes of S. mansoni worms recovered from mice vaccinated with rSm29.The figure shows real-time RT-PCR validation experiment for six genes down-regulated in S. mansoni worms recovered from rSm29+adjuvant immunized mice (black bars) compared to worms from PBS+adjuvant injected control mice (white bars). The selected genes were: CD36-CD36-like class B scavenger receptor [S. mansoni]; Sm23-Sm23 kDa integral membrane protein [S. mansoni]; Sm14-Fatty acid-binding protein Sm14 [S. mansoni]; Superox-Superoxide dismutase [S. mansoni]; TGF-β RIP-TGF-β receptor interacting protein 1 [C. sinensis]; B-cell RAP-B-cell receptor-associated protein-like protein [S. mansoni]. Statistically significant differences of vaccinated mice compared to PBS+adjuvant control group is denoted by one asterisk (p<0.03).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2553283&req=5

pntd-0000308-g005: Transcript level changes in selected genes of S. mansoni worms recovered from mice vaccinated with rSm29.The figure shows real-time RT-PCR validation experiment for six genes down-regulated in S. mansoni worms recovered from rSm29+adjuvant immunized mice (black bars) compared to worms from PBS+adjuvant injected control mice (white bars). The selected genes were: CD36-CD36-like class B scavenger receptor [S. mansoni]; Sm23-Sm23 kDa integral membrane protein [S. mansoni]; Sm14-Fatty acid-binding protein Sm14 [S. mansoni]; Superox-Superoxide dismutase [S. mansoni]; TGF-β RIP-TGF-β receptor interacting protein 1 [C. sinensis]; B-cell RAP-B-cell receptor-associated protein-like protein [S. mansoni]. Statistically significant differences of vaccinated mice compared to PBS+adjuvant control group is denoted by one asterisk (p<0.03).
Mentions: In order to investigate the impact of rSm29 vaccination on S. mansoni, worms that were recovered from vaccinated mice had their gene expression profile analyzed using microarrays. This analysis revealed significant (q<0.01) regulation of 517 genes (Table S1) in worms recovered from mice vaccinated with adjuvanted rSm29 when compared to control mice injected with adjuvanted phosphate-buffered saline; of these, 495 genes (96%) were down-regulated and only 22 genes (4%) were up-regulated. Among down-regulated genes, several of them caught our attention and they fell into four major categories: tegument proteins (Sm23 and CD36-like class B scavenger receptor), membrane proteins (tetraspanin TE736), lipid metabolism (Sm14), receptor interacting proteins (B-cell receptor-associated protein and TGF-beta receptor interacting protein) and others (superoxide dismutase and Sm65) (Table 3). To validate the microarray data, we selected six genes (Sm23, Sm14, superoxide dismutase, CD36-like class B scavenger receptor, B-cell receptor-associated protein and TGF-β receptor interacting protein) and performed real-time RT-PCR. As demonstrated in Figure 5, real-time RT-PCR of all six tested genes confirmed the reduced expression previously determined by microarray analysis. Based on the data shown in Table 3 and Figure 5, we hypothesize that in rSm29 protected mice a reduced expression of these critical surface antigens enables the parasites to adapt to the host in the face of an ongoing antiparasite immune response developed in vaccinated animals.

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