Abstract
BackgroundSchistosoma 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.MethodsIn 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.ResultsMice 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.ConclusionThe 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.
Highlights
Schistosoma mansoni infection represents a major cause of morbidity and mortality in many areas of the developing world
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)
These include tegumental irregularities and occasional swollen knots as shown in details in Figure 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. 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
Summary
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. Most investigators examine these promising antigens in animal models individually rather than in properly adjuvanted antigen combinations. The use of the anthelmintic drug praziquantel for treatment is the cornerstone of managing the disease in infected individuals. There is currently no effective vaccine against schistosomiasis despite the innumerable efforts for its development in the last twenty-five years. Strong evidence supports the possibility of development of a vaccine against the different species of schistosomes [3,4]. Most investigators tested potential schistosomal vaccine antigens individually rather than in properly adjuvanted antigen combinations. It is unlikely that a single antigen would give the required protective results due to the complex structure of the different stages in the schistosomal life cycle besides the multiple immune responses involved
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