Limits...
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.

Show MeSH

Related in: MedlinePlus

Kinetics of specific anti-Sm29 IgG induced in mice immunized with rSm29.Sera of ten immunized mice per group were collected at days 15, 30, 45, and 90 after the first immunization and assayed by ELISA. Arrows indicate the timing of vaccination. Results are presented as the mean absorbance measured at 492nm for each group. Results represent the mean of two independent experiments. Statistically significant differences of vaccinated mice compared to PBS+adjuvant control group is denoted by one asterisk for (p<0.05).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2553283&req=5

pntd-0000308-g003: Kinetics of specific anti-Sm29 IgG induced in mice immunized with rSm29.Sera of ten immunized mice per group were collected at days 15, 30, 45, and 90 after the first immunization and assayed by ELISA. Arrows indicate the timing of vaccination. Results are presented as the mean absorbance measured at 492nm for each group. Results represent the mean of two independent experiments. Statistically significant differences of vaccinated mice compared to PBS+adjuvant control group is denoted by one asterisk for (p<0.05).

Mentions: To evaluate the level of specific IgG, IgG1 and IgG2a antibodies to Sm29 sera from ten vaccinated animals of each group were tested by ELISA. Significant titers of specific anti-Sm29 IgG antibodies were detected at all time points studied after the first immunization (Figure 3). In order to determine the IgG isotype profile induced by vaccination, specific anti-Sm29 IgG1 and IgG2a antibodies levels were also evaluated. The levels of specific IgG1 and IgG2a increased at 15, 30 and 45 days after the first immunization (Table 1). Furthermore, IgG1/IgG2a ratio was reduced at days 30 and 45 that parallels with elevated anti-Sm29 IgG2a production. The IgG1/IgG2a ratio observed in mice immunized with rSm29 can lead us to speculate that a Th1 type of immune response was induced following vaccination.


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)

Kinetics of specific anti-Sm29 IgG induced in mice immunized with rSm29.Sera of ten immunized mice per group were collected at days 15, 30, 45, and 90 after the first immunization and assayed by ELISA. Arrows indicate the timing of vaccination. Results are presented as the mean absorbance measured at 492nm for each group. Results represent the mean of two independent experiments. Statistically significant differences of vaccinated mice compared to PBS+adjuvant control group is denoted by one asterisk for (p<0.05).
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0000308-g003: Kinetics of specific anti-Sm29 IgG induced in mice immunized with rSm29.Sera of ten immunized mice per group were collected at days 15, 30, 45, and 90 after the first immunization and assayed by ELISA. Arrows indicate the timing of vaccination. Results are presented as the mean absorbance measured at 492nm for each group. Results represent the mean of two independent experiments. Statistically significant differences of vaccinated mice compared to PBS+adjuvant control group is denoted by one asterisk for (p<0.05).
Mentions: To evaluate the level of specific IgG, IgG1 and IgG2a antibodies to Sm29 sera from ten vaccinated animals of each group were tested by ELISA. Significant titers of specific anti-Sm29 IgG antibodies were detected at all time points studied after the first immunization (Figure 3). In order to determine the IgG isotype profile induced by vaccination, specific anti-Sm29 IgG1 and IgG2a antibodies levels were also evaluated. The levels of specific IgG1 and IgG2a increased at 15, 30 and 45 days after the first immunization (Table 1). Furthermore, IgG1/IgG2a ratio was reduced at days 30 and 45 that parallels with elevated anti-Sm29 IgG2a production. The IgG1/IgG2a ratio observed in mice immunized with rSm29 can lead us to speculate that a Th1 type of immune response was induced following vaccination.

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