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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

Light microscopic appearance of carmine-stained adult worms recovered from FSm14/29-immunized mice. (A) Abnormally shortened adult male worm exhibiting multiple gut dilatations (Gd). The testes were not clearly seen due to dilatations of the gut in the anterior part of the worm. (B) Slightly elongated male with bulging (arrow) in the posterior end. (C&D) Male worm demonstrating gut dilatation which hides the appearance of the testes, with ill-defined oedematous suckers, and remarkable tegumental irregularities in the worm outline. (E) An example of an elongated female. (F&G) Posterior ends of females possessing universal pronounced tegumental oedematous irregularities (arrows) or even wrinkled posterior ends. (H) Occasional swollen knots (Kn) in a female mid-body. Sparseness of the pigment content of the gut was noticed in all examined female worms with indistinct vitelline gland lobulations and ill-defined ovarian boundaries.
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Fig3: Light microscopic appearance of carmine-stained adult worms recovered from FSm14/29-immunized mice. (A) Abnormally shortened adult male worm exhibiting multiple gut dilatations (Gd). The testes were not clearly seen due to dilatations of the gut in the anterior part of the worm. (B) Slightly elongated male with bulging (arrow) in the posterior end. (C&D) Male worm demonstrating gut dilatation which hides the appearance of the testes, with ill-defined oedematous suckers, and remarkable tegumental irregularities in the worm outline. (E) An example of an elongated female. (F&G) Posterior ends of females possessing universal pronounced tegumental oedematous irregularities (arrows) or even wrinkled posterior ends. (H) Occasional swollen knots (Kn) in a female mid-body. Sparseness of the pigment content of the gut was noticed in all examined female worms with indistinct vitelline gland lobulations and ill-defined ovarian boundaries.

Mentions: Adult worms obtained from mice immunized with the unadjuvanted or poly(I:C)-adjuvanted FSm14/29 showed noticeable deformities. These include tegumental irregularities and occasional swollen knots as shown in details in FigureĀ 3 which shows representative pictures for worms recovered from the infected FSm14/29-immunized group. None of these observed deformities were detectable in adult worms recovered from all other experimental groups including the infected unvaccinated negative control group, the adjuvant group and groups immunized with the individual antigens. In addition, we found that both male and female adult worms recovered from mice previously immunized with adjuvanted or unadjuvanted FSm14/29 showed statistically significant reduction (p <0.05) in their perimeters when compared with the negative control group (data not shown).Figure 3


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)

Light microscopic appearance of carmine-stained adult worms recovered from FSm14/29-immunized mice. (A) Abnormally shortened adult male worm exhibiting multiple gut dilatations (Gd). The testes were not clearly seen due to dilatations of the gut in the anterior part of the worm. (B) Slightly elongated male with bulging (arrow) in the posterior end. (C&D) Male worm demonstrating gut dilatation which hides the appearance of the testes, with ill-defined oedematous suckers, and remarkable tegumental irregularities in the worm outline. (E) An example of an elongated female. (F&G) Posterior ends of females possessing universal pronounced tegumental oedematous irregularities (arrows) or even wrinkled posterior ends. (H) Occasional swollen knots (Kn) in a female mid-body. Sparseness of the pigment content of the gut was noticed in all examined female worms with indistinct vitelline gland lobulations and ill-defined ovarian boundaries.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Light microscopic appearance of carmine-stained adult worms recovered from FSm14/29-immunized mice. (A) Abnormally shortened adult male worm exhibiting multiple gut dilatations (Gd). The testes were not clearly seen due to dilatations of the gut in the anterior part of the worm. (B) Slightly elongated male with bulging (arrow) in the posterior end. (C&D) Male worm demonstrating gut dilatation which hides the appearance of the testes, with ill-defined oedematous suckers, and remarkable tegumental irregularities in the worm outline. (E) An example of an elongated female. (F&G) Posterior ends of females possessing universal pronounced tegumental oedematous irregularities (arrows) or even wrinkled posterior ends. (H) Occasional swollen knots (Kn) in a female mid-body. Sparseness of the pigment content of the gut was noticed in all examined female worms with indistinct vitelline gland lobulations and ill-defined ovarian boundaries.
Mentions: Adult worms obtained from mice immunized with the unadjuvanted or poly(I:C)-adjuvanted FSm14/29 showed noticeable deformities. These include tegumental irregularities and occasional swollen knots as shown in details in FigureĀ 3 which shows representative pictures for worms recovered from the infected FSm14/29-immunized group. None of these observed deformities were detectable in adult worms recovered from all other experimental groups including the infected unvaccinated negative control group, the adjuvant group and groups immunized with the individual antigens. In addition, we found that both male and female adult worms recovered from mice previously immunized with adjuvanted or unadjuvanted FSm14/29 showed statistically significant reduction (p <0.05) in their perimeters when compared with the negative control group (data not shown).Figure 3

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