Characterization and Protective Potential of the Immune Response toTaenia soliumParamyosin in a Murine Model of Cysticercosis

Abstract

Paramyosin has been proposed as a vaccine candidate in schistosomiasis and filariasis. However, limited information is available about its protective potential against cysticercosis and the immune response it induces. Immunization of mice with recombinant full-length paramyosin of Taenia solium (TPmy) results in about a 52% reduction in parasite burden after a subsequent challenge by intraperitoneal inoculation of Taenia crassiceps cysticerci. Immunization assays using recombinant fragments of TPmy, corresponding approximately to thirds on the amino, central, or carboxyl regions, suggest that protective epitopes are located mostly in the amino-end third. Proliferation assays using T cells obtained from mice immunized with the full-length recombinant TPmy also showed a preferential response to the amino-terminal fragment. In contrast, antibodies in the sera from these mice predominantly recognize epitopes located in the carboxyl-terminal fragment, being the immunoglobulin G1 subclass, the predominant antibody isotype. Characterization of the cellular immune response induced against the protective amino-terminal fragment reveals production of gamma interferon and interleukin-2, but not interleukin-4, suggesting a Th1-like profile.Paramyosin (Pmy) is a filamentous, ␣-helical, coiled-coil protein of about 100 kDa, present in some muscles of invertebrates. It is also an antigen during infections by several flatworms that are important parasites of humans and of domestic animals such as Schistosoma mansoni (10), Schistosoma japonicum (4), Taenia solium (10, 12), and Echinococcus granulosus (18). The paramyosin of T. solium (TPmy) is present in the musculature but has also been found associated with the tegument of the parasite (7). The collagen-binding and complement-inhibitory properties of TPmy have been described previously (8, 9, 11). TPmy is synthesized by the tegumentary cytons and apparently released through the cyst tegument (8). Furthermore, TPmy can be collected in the culture medium in which T. solium cysts are maintained (8), suggesting that a similar release to the host tissues might occur in vivo and that TPmy may modulate the host response through diminution of the inflammatory mediators at the host-parasite interface (8,11).Paramyosins have been proposed as vaccine candidates in a number of helminthiases including schistosomiasis (3, 20) and filariasis (14,19). Despite their protective abilities against schistosomiasis and filariasis, limited information is available on their potential as vaccines against cysticercosis. Here we report that immunization of mice with recombinant fragments of TPmy induces significant levels of protection in the murine model of cysticercosis by Taenia crassiceps. The profile of cytokine production suggests that the protective amino-terminal fragment of TPmy induces a Th1-like immune response. MATERIALS AND METHODSAnimal model. Mice used in all experiments were 4-to 6-week-old female BALB/c AnN strain mice. The ORF strain of T. crassiceps was maintained by consecutive passa...

Molecular Cloning and Characterization of a Paramyosin from Clonorchis sinensis

“…This coincides with previous studies on the vaccination/immunization of paramyosins from other helminth parasites [11,27,38,39]. Due to its high level of immunogenicity, paramyosin has been proposed as potential vaccine candidate in a number of helminthiases, including schistosomiasis [20,21,28,39,40], filariasis [22,23] and cysticercosis [27,29]. We also found that rats vaccinated with rCsPmy (100 mg/rat) and challenged with 100 metacercariae of C. sinensis showed reduced worm burden (11.6-20.6%) compared to control rats (our unpublished data).…”

“…These results suggested that paramyosin of helminth parasites are multifunctional proteins acting not only as structural protein in muscle layers to control their contraction physiologically, but also as an immunoregulatory molecule interacting with the host immune system. In addition, immunogenic properties of paramyosins of helminth parasites make them potential vaccine candidates [11,[20][21][22][23][24][25][26][27][28][29][30].…”

Inhibition of the Complement Membrane Attack Complex bySchistosoma mansoniParamyosin

“…Paramyosin is considered a vaccine candidate against schistosomiasis mansoni (42), schistosomiasis japonicum (24,46), filariasis (29,38), and cysticercosis (57). It acts as one of the major schistosome immunogens during infection with S. mansoni in mice (27) and humans (47).…”

Genetic Vaccination against Murine Cysticercosis by Using a Plasmid Vector CarryingTaenia soliumParamyosin

“…Genetic vaccines are particularly appealing for applications in developing countries as they can be inexpensive to produce and store (5). In the present study, we evaluated the use of genetic immunization with the amino-terminal fragment of T. solium paramyosin (VW2-1), which was previously shown to be protective (15), as an alternative strategy for vaccination in the murine model of Taenia crassiceps cysticercosis.…”

“…A strong effort is currently being directed toward the development of an effective vaccine against porcine cysticercosis. A number of strategies have been proposed, including the use of parasite crude extracts (9,17), recombinant proteins (2,3,15), synthetic peptides (4), phage display (8), and genetic immunization (10,18). Genetic vaccines are particularly appealing for applications in developing countries as they can be inexpensive to produce and store (5).…”