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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. mansonimale worms recovered from unimmunized group (A and B) and from FSm14/29-immunized group (C-H). (A) A male worm obtained from infected control group showing normal body configuration, typical oral and ventral suckers, and distinct tegumental structure with evident normal spines on the dorsal surface behind the beginning of the gynecophoric canal (Gc), X200. (B) Tegument of the middle dorsolateral region showing numerous large tubercles, each bearing numerous spines. Intertubercular ridges and ciliated sensory papillae are obvious, X 5,000. (C) Tegumental surface alterations in adult male from infected FSm14/29-immunized group demonstrating widening of the gynecophoric canal (Gc), loss of some areas of the tegumental tubercles and ridges (arrows), surface erosions (Er), tegumental tear (Tt), and bossing of the terminal end of the worm, X200. The posterior end shows several areas of bulging. (D) Higher magnification of a conspicuously widened gynecophoric canal, along with restricted spine loss (arrow), X5,000. (E) Swollen area between the oral and ventral suckers showing circumferentially arranged ridges with sensory papillae rows. An evident dorsal dimple is witnessed (Dp), along with suckers oedema and blebbing, X2,000. (F) Eminent flattening of the dorsal tubercles along with shortened spines which were irregularly positioned or even lost in some areas (arrows), X5,000. (G) Altered dorsal tubercles revealed peeling and focal sloughing (Sl) of their tegument. Tubercular and inter-tubercular coarse bumpy tegumental irregularities were observed, with occasional burst of some blistered tubercles, X5,000. (H) Host leucocytic (arrows) attachment to the worm surface with evident spine blunting, X7500.
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Fig4: Scanning electron micrographs of adultS. mansonimale worms recovered from unimmunized group (A and B) and from FSm14/29-immunized group (C-H). (A) A male worm obtained from infected control group showing normal body configuration, typical oral and ventral suckers, and distinct tegumental structure with evident normal spines on the dorsal surface behind the beginning of the gynecophoric canal (Gc), X200. (B) Tegument of the middle dorsolateral region showing numerous large tubercles, each bearing numerous spines. Intertubercular ridges and ciliated sensory papillae are obvious, X 5,000. (C) Tegumental surface alterations in adult male from infected FSm14/29-immunized group demonstrating widening of the gynecophoric canal (Gc), loss of some areas of the tegumental tubercles and ridges (arrows), surface erosions (Er), tegumental tear (Tt), and bossing of the terminal end of the worm, X200. The posterior end shows several areas of bulging. (D) Higher magnification of a conspicuously widened gynecophoric canal, along with restricted spine loss (arrow), X5,000. (E) Swollen area between the oral and ventral suckers showing circumferentially arranged ridges with sensory papillae rows. An evident dorsal dimple is witnessed (Dp), along with suckers oedema and blebbing, X2,000. (F) Eminent flattening of the dorsal tubercles along with shortened spines which were irregularly positioned or even lost in some areas (arrows), X5,000. (G) Altered dorsal tubercles revealed peeling and focal sloughing (Sl) of their tegument. Tubercular and inter-tubercular coarse bumpy tegumental irregularities were observed, with occasional burst of some blistered tubercles, X5,000. (H) Host leucocytic (arrows) attachment to the worm surface with evident spine blunting, X7500.

Mentions: Male adult worms obtained from unimmunized control mice showed normal configuration and tegumental structure, with evident normal spines on the dorsal surface behind the beginning of the gynecophoric canal (Figure 4A). The dorsolateral surface of the mid-body was covered by tubercles of uniform size and distribution, covered by typical spines and interspaced with tegumental ridges and ciliated sensory papillae (Figure 4B).Figure 4


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. mansonimale worms recovered from unimmunized group (A and B) and from FSm14/29-immunized group (C-H). (A) A male worm obtained from infected control group showing normal body configuration, typical oral and ventral suckers, and distinct tegumental structure with evident normal spines on the dorsal surface behind the beginning of the gynecophoric canal (Gc), X200. (B) Tegument of the middle dorsolateral region showing numerous large tubercles, each bearing numerous spines. Intertubercular ridges and ciliated sensory papillae are obvious, X 5,000. (C) Tegumental surface alterations in adult male from infected FSm14/29-immunized group demonstrating widening of the gynecophoric canal (Gc), loss of some areas of the tegumental tubercles and ridges (arrows), surface erosions (Er), tegumental tear (Tt), and bossing of the terminal end of the worm, X200. The posterior end shows several areas of bulging. (D) Higher magnification of a conspicuously widened gynecophoric canal, along with restricted spine loss (arrow), X5,000. (E) Swollen area between the oral and ventral suckers showing circumferentially arranged ridges with sensory papillae rows. An evident dorsal dimple is witnessed (Dp), along with suckers oedema and blebbing, X2,000. (F) Eminent flattening of the dorsal tubercles along with shortened spines which were irregularly positioned or even lost in some areas (arrows), X5,000. (G) Altered dorsal tubercles revealed peeling and focal sloughing (Sl) of their tegument. Tubercular and inter-tubercular coarse bumpy tegumental irregularities were observed, with occasional burst of some blistered tubercles, X5,000. (H) Host leucocytic (arrows) attachment to the worm surface with evident spine blunting, X7500.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: Scanning electron micrographs of adultS. mansonimale worms recovered from unimmunized group (A and B) and from FSm14/29-immunized group (C-H). (A) A male worm obtained from infected control group showing normal body configuration, typical oral and ventral suckers, and distinct tegumental structure with evident normal spines on the dorsal surface behind the beginning of the gynecophoric canal (Gc), X200. (B) Tegument of the middle dorsolateral region showing numerous large tubercles, each bearing numerous spines. Intertubercular ridges and ciliated sensory papillae are obvious, X 5,000. (C) Tegumental surface alterations in adult male from infected FSm14/29-immunized group demonstrating widening of the gynecophoric canal (Gc), loss of some areas of the tegumental tubercles and ridges (arrows), surface erosions (Er), tegumental tear (Tt), and bossing of the terminal end of the worm, X200. The posterior end shows several areas of bulging. (D) Higher magnification of a conspicuously widened gynecophoric canal, along with restricted spine loss (arrow), X5,000. (E) Swollen area between the oral and ventral suckers showing circumferentially arranged ridges with sensory papillae rows. An evident dorsal dimple is witnessed (Dp), along with suckers oedema and blebbing, X2,000. (F) Eminent flattening of the dorsal tubercles along with shortened spines which were irregularly positioned or even lost in some areas (arrows), X5,000. (G) Altered dorsal tubercles revealed peeling and focal sloughing (Sl) of their tegument. Tubercular and inter-tubercular coarse bumpy tegumental irregularities were observed, with occasional burst of some blistered tubercles, X5,000. (H) Host leucocytic (arrows) attachment to the worm surface with evident spine blunting, X7500.
Mentions: Male adult worms obtained from unimmunized control mice showed normal configuration and tegumental structure, with evident normal spines on the dorsal surface behind the beginning of the gynecophoric canal (Figure 4A). The dorsolateral surface of the mid-body was covered by tubercles of uniform size and distribution, covered by typical spines and interspaced with tegumental ridges and ciliated sensory papillae (Figure 4B).Figure 4

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