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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

Liver histological sections form infected unimmunized control mice (A-E) and FSm14/29-immunized mice (F-J). (A) Liver section of infected unimmunized mouse showing Kupffer cells’ hyperplasia (H&E x100). (B) Liver section of an infected mouse showing hydropic degeneration and ballooning of hepatic cells (H&E x400). (C) Liver section of an infected mouse showing lymphocytic infiltration of portal tract with marked dilatation and proliferation of blood vessels (H&E x100). (D) Liver section of an infected mouse showing numerous large size cellular granulomata (H&E x100). (E) Liver section of an infected mouse showing non-degenerated well developed S. mansoni egg trapped within cellular granuloma (MT x400). (F) Liver section of infected FSm14/29-immunized mouse showing decreased number and size of cellular granulomata surrounding degenerated eggs (H&E x100). (G) Liver section of infected FSm14/29-immunized mouse showing lesser degree of cellular swelling and inflammatory infiltration (H&E x400). (H) Liver section of infected FSm14/29-immunized mouse showing regenerative activity represented by hepatocyte binucleation (arrows) (H&E x400). (I & J) Liver sections of infected FSm14/29-immunized mouse showing small well-circumscribed fibrous granulomata with degenerated eggs (MT X400).
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Fig6: Liver histological sections form infected unimmunized control mice (A-E) and FSm14/29-immunized mice (F-J). (A) Liver section of infected unimmunized mouse showing Kupffer cells’ hyperplasia (H&E x100). (B) Liver section of an infected mouse showing hydropic degeneration and ballooning of hepatic cells (H&E x400). (C) Liver section of an infected mouse showing lymphocytic infiltration of portal tract with marked dilatation and proliferation of blood vessels (H&E x100). (D) Liver section of an infected mouse showing numerous large size cellular granulomata (H&E x100). (E) Liver section of an infected mouse showing non-degenerated well developed S. mansoni egg trapped within cellular granuloma (MT x400). (F) Liver section of infected FSm14/29-immunized mouse showing decreased number and size of cellular granulomata surrounding degenerated eggs (H&E x100). (G) Liver section of infected FSm14/29-immunized mouse showing lesser degree of cellular swelling and inflammatory infiltration (H&E x400). (H) Liver section of infected FSm14/29-immunized mouse showing regenerative activity represented by hepatocyte binucleation (arrows) (H&E x400). (I & J) Liver sections of infected FSm14/29-immunized mouse showing small well-circumscribed fibrous granulomata with degenerated eggs (MT X400).

Mentions: Liver sections of unimmunized infected control group showed typical histopathological features as shown in Figure 6A-E. Abundant large irregular cellular granulomata, in which S. mansoni eggs were surrounded mainly by epithelioid cells and infiltrating lymphocytes were observed with no sign of formation of collagen fibers. In groups immunized with unadjuvanted or poly(I:C)-adjuvanted FSm14/29, fewer and smaller cellular granulomata were seen and parenchymal changes were milder than controls (Figure 6F-J). Degenerated eggs were surrounded mostly by numerous eosinophils, neutrophils, lymphocytes and few epithelioid cells with evident fibroblastic proliferation (Figure 6 I and J).Figure 6


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)

Liver histological sections form infected unimmunized control mice (A-E) and FSm14/29-immunized mice (F-J). (A) Liver section of infected unimmunized mouse showing Kupffer cells’ hyperplasia (H&E x100). (B) Liver section of an infected mouse showing hydropic degeneration and ballooning of hepatic cells (H&E x400). (C) Liver section of an infected mouse showing lymphocytic infiltration of portal tract with marked dilatation and proliferation of blood vessels (H&E x100). (D) Liver section of an infected mouse showing numerous large size cellular granulomata (H&E x100). (E) Liver section of an infected mouse showing non-degenerated well developed S. mansoni egg trapped within cellular granuloma (MT x400). (F) Liver section of infected FSm14/29-immunized mouse showing decreased number and size of cellular granulomata surrounding degenerated eggs (H&E x100). (G) Liver section of infected FSm14/29-immunized mouse showing lesser degree of cellular swelling and inflammatory infiltration (H&E x400). (H) Liver section of infected FSm14/29-immunized mouse showing regenerative activity represented by hepatocyte binucleation (arrows) (H&E x400). (I & J) Liver sections of infected FSm14/29-immunized mouse showing small well-circumscribed fibrous granulomata with degenerated eggs (MT X400).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig6: Liver histological sections form infected unimmunized control mice (A-E) and FSm14/29-immunized mice (F-J). (A) Liver section of infected unimmunized mouse showing Kupffer cells’ hyperplasia (H&E x100). (B) Liver section of an infected mouse showing hydropic degeneration and ballooning of hepatic cells (H&E x400). (C) Liver section of an infected mouse showing lymphocytic infiltration of portal tract with marked dilatation and proliferation of blood vessels (H&E x100). (D) Liver section of an infected mouse showing numerous large size cellular granulomata (H&E x100). (E) Liver section of an infected mouse showing non-degenerated well developed S. mansoni egg trapped within cellular granuloma (MT x400). (F) Liver section of infected FSm14/29-immunized mouse showing decreased number and size of cellular granulomata surrounding degenerated eggs (H&E x100). (G) Liver section of infected FSm14/29-immunized mouse showing lesser degree of cellular swelling and inflammatory infiltration (H&E x400). (H) Liver section of infected FSm14/29-immunized mouse showing regenerative activity represented by hepatocyte binucleation (arrows) (H&E x400). (I & J) Liver sections of infected FSm14/29-immunized mouse showing small well-circumscribed fibrous granulomata with degenerated eggs (MT X400).
Mentions: Liver sections of unimmunized infected control group showed typical histopathological features as shown in Figure 6A-E. Abundant large irregular cellular granulomata, in which S. mansoni eggs were surrounded mainly by epithelioid cells and infiltrating lymphocytes were observed with no sign of formation of collagen fibers. In groups immunized with unadjuvanted or poly(I:C)-adjuvanted FSm14/29, fewer and smaller cellular granulomata were seen and parenchymal changes were milder than controls (Figure 6F-J). Degenerated eggs were surrounded mostly by numerous eosinophils, neutrophils, lymphocytes and few epithelioid cells with evident fibroblastic proliferation (Figure 6 I and J).Figure 6

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