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Fusion protein comprised of the two schistosomal antigens, Sm14 and Sm29, provides significant protection against Schistosoma mansoni in murine infection model.

Mossallam SF, Amer EI, Ewaisha RE, Khalil AM, Aboushleib HM, Bahey-El-Din M - BMC Infect. Dis. (2015)

Bottom Line: In the present study, we made a recombinant fusion protein comprised of the promising schistosomal antigens Sm14 and Sm29.In addition, significant reduction of tissue egg burdens was observed in mice immunized with the fusion protein when compared with the infected saline/adjuvant negative control groups and groups immunized with the individual Sm14 and Sm29 antigens.The findings presented in this study highlight the importance of the fusion protein FSm14/29 as a potential vaccine candidate that is worthy of further investigation.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt. mossallamsh@hotmail.com.

ABSTRACT

Background: Schistosoma mansoni infection represents a major cause of morbidity and mortality in many areas of the developing world. Effective vaccines against schistosomiasis are not available and disease management relies mainly on treatment with the anthelmintic drug praziquantel. Several promising schistosomal antigens have been evaluated for vaccine efficacy such as Sm14, Sm29 and tetraspanins. However, most investigators examine these promising antigens in animal models individually rather than in properly adjuvanted antigen combinations.

Methods: In the present study, we made a recombinant fusion protein comprised of the promising schistosomal antigens Sm14 and Sm29. The fusion protein, FSm14/29, was administered to Swiss albino mice either unadjuvanted or adjuvanted with polyinosinic-polycytidylic acid adjuvant, poly(I:C). Mice were challenged with S. mansoni cercariae and different parasitological/immunological parameters were assessed seven weeks post-challenge. Data were analyzed using the ANOVA test with post-hoc Tukey-Kramer test.

Results: Mice pre-immunized with unadjuvanted or poly(I:C)-adjuvanted fusion protein showed reduction of adult worm burden of 44.7 and 48.4%, respectively. In addition, significant reduction of tissue egg burdens was observed in mice immunized with the fusion protein when compared with the infected saline/adjuvant negative control groups and groups immunized with the individual Sm14 and Sm29 antigens. Light microscope and scanning electron microscope (SEM) investigation of adult worms recovered from FSm14/29-immunized mice revealed appreciable morphological damage and tegumental deformities. Histopathological examination of liver sections of immunized mice demonstrated reduced granulomatous and inflammatory reactions when compared with infected unvaccinated mice or mice immunized with the individual Sm14 and Sm29 antigens.

Conclusion: The findings presented in this study highlight the importance of the fusion protein FSm14/29 as a potential vaccine candidate that is worthy of further investigation.

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Related in: MedlinePlus

Antigen-specific IgG1 and IgG2a antibodies in sera of immunized mice. ELISA plates were coated with corresponding antigens and serum samples were tested for the presence of anti-antigen IgG1 (A, B and C) and anti-antigen IgG2a (D, E and F). The shown results are at 1/250 serum dilution where error bars represent the mean reading +/− SE (standard error of the mean). (*) p < 0.05; (**) p < 0.01; (***) p < 0.001 by the ANOVA test and post-hoc Tukey-Kramer test. Asterisks are shown only for groups that showed significant statistical difference.
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Fig2: Antigen-specific IgG1 and IgG2a antibodies in sera of immunized mice. ELISA plates were coated with corresponding antigens and serum samples were tested for the presence of anti-antigen IgG1 (A, B and C) and anti-antigen IgG2a (D, E and F). The shown results are at 1/250 serum dilution where error bars represent the mean reading +/− SE (standard error of the mean). (*) p < 0.05; (**) p < 0.01; (***) p < 0.001 by the ANOVA test and post-hoc Tukey-Kramer test. Asterisks are shown only for groups that showed significant statistical difference.

Mentions: Serum samples were collected from immunized mice two weeks after the last booster for specific antibody detection by ELISA. The single antigens Sm14 and Sm29 elicited specific IgG1 antibodies in immunized mice mainly in groups vaccinated with corresponding adjuvanted antigens when compared with the negative control and poly(I:C) groups (Figure 2A and B). The fusion antigen FSm14/29 stimulated significant specific IgG1 in animals immunized with unadjuvanted or poly(I:C)-adjuvanted fusion antigen when compared with the negative control and poly(I:C) groups (Figure 2C). Upon comparing the results of IgG1 against FSm14/29 and the individual antigens, it was found that anti-Sm14 IgG1 antibodies (mean absorbance 0.95) was significantly higher (p = 0.03) than anti-FSm14/29 IgG1 (mean absorbance 0.67) in groups immunized with the poly(I:C)-adjuvanted corresponding antigens (Figures 2A and C). On the other hand, specific IgG2a antibody levels were not statistically significant in all mice groups except for the poly(I:C)-adjuvanted Sm14 vaccinated group when compared to the saline-treated negative control group (Figure 2D-F). The mean absorbance values for IgG2a ELISA detection were generally higher in mice immunized with poly(I:C)-adjuvanted antigens than in mice immunized with unadjuvanted antigens, but difference was not statistically significant (Figure 2D-F).Figure 2


Fusion protein comprised of the two schistosomal antigens, Sm14 and Sm29, provides significant protection against Schistosoma mansoni in murine infection model.

Mossallam SF, Amer EI, Ewaisha RE, Khalil AM, Aboushleib HM, Bahey-El-Din M - BMC Infect. Dis. (2015)

Antigen-specific IgG1 and IgG2a antibodies in sera of immunized mice. ELISA plates were coated with corresponding antigens and serum samples were tested for the presence of anti-antigen IgG1 (A, B and C) and anti-antigen IgG2a (D, E and F). The shown results are at 1/250 serum dilution where error bars represent the mean reading +/− SE (standard error of the mean). (*) p < 0.05; (**) p < 0.01; (***) p < 0.001 by the ANOVA test and post-hoc Tukey-Kramer test. Asterisks are shown only for groups that showed significant statistical difference.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4389862&req=5

Fig2: Antigen-specific IgG1 and IgG2a antibodies in sera of immunized mice. ELISA plates were coated with corresponding antigens and serum samples were tested for the presence of anti-antigen IgG1 (A, B and C) and anti-antigen IgG2a (D, E and F). The shown results are at 1/250 serum dilution where error bars represent the mean reading +/− SE (standard error of the mean). (*) p < 0.05; (**) p < 0.01; (***) p < 0.001 by the ANOVA test and post-hoc Tukey-Kramer test. Asterisks are shown only for groups that showed significant statistical difference.
Mentions: Serum samples were collected from immunized mice two weeks after the last booster for specific antibody detection by ELISA. The single antigens Sm14 and Sm29 elicited specific IgG1 antibodies in immunized mice mainly in groups vaccinated with corresponding adjuvanted antigens when compared with the negative control and poly(I:C) groups (Figure 2A and B). The fusion antigen FSm14/29 stimulated significant specific IgG1 in animals immunized with unadjuvanted or poly(I:C)-adjuvanted fusion antigen when compared with the negative control and poly(I:C) groups (Figure 2C). Upon comparing the results of IgG1 against FSm14/29 and the individual antigens, it was found that anti-Sm14 IgG1 antibodies (mean absorbance 0.95) was significantly higher (p = 0.03) than anti-FSm14/29 IgG1 (mean absorbance 0.67) in groups immunized with the poly(I:C)-adjuvanted corresponding antigens (Figures 2A and C). On the other hand, specific IgG2a antibody levels were not statistically significant in all mice groups except for the poly(I:C)-adjuvanted Sm14 vaccinated group when compared to the saline-treated negative control group (Figure 2D-F). The mean absorbance values for IgG2a ELISA detection were generally higher in mice immunized with poly(I:C)-adjuvanted antigens than in mice immunized with unadjuvanted antigens, but difference was not statistically significant (Figure 2D-F).Figure 2

Bottom Line: In the present study, we made a recombinant fusion protein comprised of the promising schistosomal antigens Sm14 and Sm29.In addition, significant reduction of tissue egg burdens was observed in mice immunized with the fusion protein when compared with the infected saline/adjuvant negative control groups and groups immunized with the individual Sm14 and Sm29 antigens.The findings presented in this study highlight the importance of the fusion protein FSm14/29 as a potential vaccine candidate that is worthy of further investigation.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt. mossallamsh@hotmail.com.

ABSTRACT

Background: Schistosoma mansoni infection represents a major cause of morbidity and mortality in many areas of the developing world. Effective vaccines against schistosomiasis are not available and disease management relies mainly on treatment with the anthelmintic drug praziquantel. Several promising schistosomal antigens have been evaluated for vaccine efficacy such as Sm14, Sm29 and tetraspanins. However, most investigators examine these promising antigens in animal models individually rather than in properly adjuvanted antigen combinations.

Methods: In the present study, we made a recombinant fusion protein comprised of the promising schistosomal antigens Sm14 and Sm29. The fusion protein, FSm14/29, was administered to Swiss albino mice either unadjuvanted or adjuvanted with polyinosinic-polycytidylic acid adjuvant, poly(I:C). Mice were challenged with S. mansoni cercariae and different parasitological/immunological parameters were assessed seven weeks post-challenge. Data were analyzed using the ANOVA test with post-hoc Tukey-Kramer test.

Results: Mice pre-immunized with unadjuvanted or poly(I:C)-adjuvanted fusion protein showed reduction of adult worm burden of 44.7 and 48.4%, respectively. In addition, significant reduction of tissue egg burdens was observed in mice immunized with the fusion protein when compared with the infected saline/adjuvant negative control groups and groups immunized with the individual Sm14 and Sm29 antigens. Light microscope and scanning electron microscope (SEM) investigation of adult worms recovered from FSm14/29-immunized mice revealed appreciable morphological damage and tegumental deformities. Histopathological examination of liver sections of immunized mice demonstrated reduced granulomatous and inflammatory reactions when compared with infected unvaccinated mice or mice immunized with the individual Sm14 and Sm29 antigens.

Conclusion: The findings presented in this study highlight the importance of the fusion protein FSm14/29 as a potential vaccine candidate that is worthy of further investigation.

Show MeSH
Related in: MedlinePlus