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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

Scanning electron micrographs of adultS. mansonifemale worms recovered from unimmunized group (A) and from FSm14/29-immunized group (B-F). (A) The dorsolateral surface of a female recovered from the unimmunized control group showing fine circular ridges interspaced with regular clefts and carrying conspicuous sensory bulbs (Sb), X3,500. (B) The anterior end of a female worm recovered from FSm14/29-immunized animals exhibiting extensive swelling of the forebody tegument, with evident strangulation (thick arrow), associated with small sized blebbings (Bl) in the lips of their suckers. Spines lining the edematous suckers were short, irregularly positioned and chubby in appearance (thin arrow), X500. (C) A convoluted female expressing irregularly positioned constrictions in various areas of its body (arrows), besides loss of the mid-body circular ridges with complete destruction of the external surface of the forebody, X750. (D) Kinky female surface swellings alternating with dimples (Dp), furrows (Fr), gappings (Ga), and wrinkling (Wr), X750. (E) Higher magnification verifying that the linear transverse tegumental ridges encircling the body worm were replaced by swelling induced loosing of the clefts, and fusions of ridges. This resulted in the formation of long irregular and disorganized splits, X3,500. (F) Host leucocytes attached to the tegument of the female surfaces (arrows), X7,500.
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Fig5: Scanning electron micrographs of adultS. mansonifemale worms recovered from unimmunized group (A) and from FSm14/29-immunized group (B-F). (A) The dorsolateral surface of a female recovered from the unimmunized control group showing fine circular ridges interspaced with regular clefts and carrying conspicuous sensory bulbs (Sb), X3,500. (B) The anterior end of a female worm recovered from FSm14/29-immunized animals exhibiting extensive swelling of the forebody tegument, with evident strangulation (thick arrow), associated with small sized blebbings (Bl) in the lips of their suckers. Spines lining the edematous suckers were short, irregularly positioned and chubby in appearance (thin arrow), X500. (C) A convoluted female expressing irregularly positioned constrictions in various areas of its body (arrows), besides loss of the mid-body circular ridges with complete destruction of the external surface of the forebody, X750. (D) Kinky female surface swellings alternating with dimples (Dp), furrows (Fr), gappings (Ga), and wrinkling (Wr), X750. (E) Higher magnification verifying that the linear transverse tegumental ridges encircling the body worm were replaced by swelling induced loosing of the clefts, and fusions of ridges. This resulted in the formation of long irregular and disorganized splits, X3,500. (F) Host leucocytes attached to the tegument of the female surfaces (arrows), X7,500.

Mentions: Figure 5 shows representative SEM images of female worms obtained from control unimmunized mice and from mice immunized with the fusion protein. The tegumental surface of female worms isolated from unimmunized mice was generally smooth with fine circular ridges interspaced with regular clefts and was carrying conspicuous sensory bulbs throughout the dorsal surface (Figure 5A). On the other hand, adult female worms obtained from FSm14/29-immunized mice exhibited drastic alterations in the form of extensive swelling of the forebody tegument associated with edema and small-sized blebbings in the lips of their suckers. Spines lining the suckers were short, irregularly positioned and chubby in appearance (Figure 5B). Furthermore, females were convoluted expressing irregularly positioned constrictions in various areas of their bodies (Figure 5C). Their surfaces showed swellings alternating with dimples and depressions, gappings, and wrinkling (Figure 5D). Higher magnification verified that the linear transverse tegumental ridges encircling the worm body were not observable, being replaced by swelling induced loosing of the clefts, and fusions of ridges. This resulted in the formation of long irregular and disorganized splits (Figure 5E). Similar to altered males, it was highly evident that host leucocytes were attached to the body of the female worms in various areas (Figure 5F).Figure 5


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)

Scanning electron micrographs of adultS. mansonifemale worms recovered from unimmunized group (A) and from FSm14/29-immunized group (B-F). (A) The dorsolateral surface of a female recovered from the unimmunized control group showing fine circular ridges interspaced with regular clefts and carrying conspicuous sensory bulbs (Sb), X3,500. (B) The anterior end of a female worm recovered from FSm14/29-immunized animals exhibiting extensive swelling of the forebody tegument, with evident strangulation (thick arrow), associated with small sized blebbings (Bl) in the lips of their suckers. Spines lining the edematous suckers were short, irregularly positioned and chubby in appearance (thin arrow), X500. (C) A convoluted female expressing irregularly positioned constrictions in various areas of its body (arrows), besides loss of the mid-body circular ridges with complete destruction of the external surface of the forebody, X750. (D) Kinky female surface swellings alternating with dimples (Dp), furrows (Fr), gappings (Ga), and wrinkling (Wr), X750. (E) Higher magnification verifying that the linear transverse tegumental ridges encircling the body worm were replaced by swelling induced loosing of the clefts, and fusions of ridges. This resulted in the formation of long irregular and disorganized splits, X3,500. (F) Host leucocytes attached to the tegument of the female surfaces (arrows), X7,500.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig5: Scanning electron micrographs of adultS. mansonifemale worms recovered from unimmunized group (A) and from FSm14/29-immunized group (B-F). (A) The dorsolateral surface of a female recovered from the unimmunized control group showing fine circular ridges interspaced with regular clefts and carrying conspicuous sensory bulbs (Sb), X3,500. (B) The anterior end of a female worm recovered from FSm14/29-immunized animals exhibiting extensive swelling of the forebody tegument, with evident strangulation (thick arrow), associated with small sized blebbings (Bl) in the lips of their suckers. Spines lining the edematous suckers were short, irregularly positioned and chubby in appearance (thin arrow), X500. (C) A convoluted female expressing irregularly positioned constrictions in various areas of its body (arrows), besides loss of the mid-body circular ridges with complete destruction of the external surface of the forebody, X750. (D) Kinky female surface swellings alternating with dimples (Dp), furrows (Fr), gappings (Ga), and wrinkling (Wr), X750. (E) Higher magnification verifying that the linear transverse tegumental ridges encircling the body worm were replaced by swelling induced loosing of the clefts, and fusions of ridges. This resulted in the formation of long irregular and disorganized splits, X3,500. (F) Host leucocytes attached to the tegument of the female surfaces (arrows), X7,500.
Mentions: Figure 5 shows representative SEM images of female worms obtained from control unimmunized mice and from mice immunized with the fusion protein. The tegumental surface of female worms isolated from unimmunized mice was generally smooth with fine circular ridges interspaced with regular clefts and was carrying conspicuous sensory bulbs throughout the dorsal surface (Figure 5A). On the other hand, adult female worms obtained from FSm14/29-immunized mice exhibited drastic alterations in the form of extensive swelling of the forebody tegument associated with edema and small-sized blebbings in the lips of their suckers. Spines lining the suckers were short, irregularly positioned and chubby in appearance (Figure 5B). Furthermore, females were convoluted expressing irregularly positioned constrictions in various areas of their bodies (Figure 5C). Their surfaces showed swellings alternating with dimples and depressions, gappings, and wrinkling (Figure 5D). Higher magnification verified that the linear transverse tegumental ridges encircling the worm body were not observable, being replaced by swelling induced loosing of the clefts, and fusions of ridges. This resulted in the formation of long irregular and disorganized splits (Figure 5E). Similar to altered males, it was highly evident that host leucocytes were attached to the body of the female worms in various areas (Figure 5F).Figure 5

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