Synthetic peptide-targeted selection of phage display mimotopes highlights immunogenic features of α-helical vs non-helical epitopes of Taenia solium paramyosin: implications for parasite- and host-protective roles of the protein.

Paramyosin of the pig-human parasite Taenia solium (TPmy) is a α-helical protein located on the worm surface that is suggested to fulfill an immunomodulatory role protecting the parasite against host immune system. Besides, in challenging experiments the protein shows a vaccine potential. These observations imply that TPmy harbors antigenic determinants for each of these contrasting actions. However the suggestion was not given a support from experimental data because respective epitopes have not been described thus far. To circumvent this difficulty, we use synthetic peptides with sequences of regions composed of α-helical or linear structure to induce rabbit antibody responses for phage-display mapping of epitope core amino-acid sets. Antibodies to α-helical regions were weak binders and M13 phage-displayed peptides selected by them from two different libraries exhibited no amino-acid similarities with the original protein site. In contrast, the antibodies produced in response to non-helical segment within α-helical structure were better binders and selectors of perfect structural mimics of the protein site. This first phage display epitope analysis of TPmy supports the notion that the rod-like α-helix, which encompasses over 90% of the total amino acids, may serve as an immunomodulatory shield that protects the parasite. Further, the seven non-helical segments of the TPmy molecule may represent the only anti-parasite discrete immunogenic epitopes whose representative mimotopes can be utilized in development of pure epitope vaccines.

Genetic vaccination against murine cysticercosis by using a plasmid vector carrying Taenia solium paramyosin.

A plasmid vector carrying the immunoprotective amino-terminal fragment of Taenia solium paramyosin (VW2-1) was designed for genetic vaccination studies. Mice that were genetically immunized with VW2-1 and challenged by intraperitoneal inoculation of Taenia crassiceps cysticerci showed 43 to 48% reductions in the parasite burden, values which were similar to values obtained previously when the recombinant protein was used.

[Toward development of a Taenia solium paramyosin-based vaccine against porcine cysticercosis]. / Hacia el desarrollo de una vacuna en contra de la cisticercosis porcina basada en la paramiosina de Taenia solium.

Taenia solium paramyosin (TPmy) is a prominent 100 kDa antigen in human and porcine cysticercosis. TPmy is an alpha-helical coiled coil protein present in muscle and tegumentary structures of T. solium cysticerci. TPmy has the property of binding C1q resulting in inhibition of the complement cascade. TPmy probably binds C1q through its collagen-like domains and could be involved in a parasite strategy to modulate host immune response. Humoral immune response against TPmy is prefrentially directed against carboxyl terminal end in humans and mice, whereas amino terminal end of TPmy preferentially induces a Th1-related cellular immune response. Protection studies in murine model of cysticercosis showed that the amino terminal end fragment of TPmy induces approximately 60% protection against an i.p. challenge with Taenia crassiceps cysts when mice are immunized with recombinant fragments of TPmy. Initial protection studies using genetic immunization showed that amino terminal end fragment of TPmy cloned into a plasmid expression vector with a cytomegalovirus promoter, together with IL-12-expressing plasmids induced 79% protection, suggesting that this kind of TPmy-immunization might result in development of a cost-effective vaccine against cysticercosis.

Hacia el desarrollo de una vacuna en contra de la cisticercosis porcina basada en la paramiosina de Taenia solium

La paramiosina de Taenia solium (TPmy) es un antígeno inmunodominante de la cisticercosis humana y porcina. Se trata de una proteína de 100 kDa con una estructura alfa-hélice superenrollada asociada al músculo y a estructuras tegumentarias del cisticerco. La TPmy tiene la propiedad de unirse al C1q e inhibir la cascada del complemento. La TPmy probablemente se une al C1q a través sus dominios tipo colágena y podría estar relacionada con una estrategia parasitaria para modular la respuesta inmune del huésped. En el hombre y en el ratón, la respuesta inmune humoral en contra de la TPmy está preferentemente dirigida hacia el extremo carboxilo terminal mientras que el extremo amino terminal de la TPmy induce una respuesta protectora celular de tipo Th1. Ensayos de protección en el modelo murino de cisticercosis en ratones inmunizados con fragmentos recombinantes de TPmy revelaron que el extremo amino terminal induce alrededor de 60% de protección en contra de un reto intraperitoneal con cisticercos de Taenia crassiceps. Ensayos preliminares de protección por inmunización génica revelaron que el extremo amino terminal de la TPmy clonado en un vector plasmídico con un promotor de citomegalovirus induce alrededor de 79% de protección, junto con plásmidos para la expresión de IL-12, sugiriendo que este tipo de inmunización con TPmy puede resultar en el desarrollo de una vacuna eficaz y económica en contra de la cisticercosis.

Taenia solium paramyosin (TPmy) is a prominent 100 kDa antigen in human and porcine cysticercosis. TPmy is an α-helical coiled coil protein present in muscle and tegumentary structures of T. solium cysticerci. TPmy has the property of binding C1q resulting in inhibition of the complement cascade. TPmy probably binds C1q through its collagen-like domains and could be involved in a parasite strategy to modulate host immune response. Humoral immune response against TPmy is preferentially directed against carboxyl terminal end in humans and mice, whereas amino terminal end of TPmy preferentially induces a Th1-related cellular immune response. Protection studies in murine model of cysticercosis showed that the amino terminal end fragment of TPmy induces approximately 60% protection against an i.p. challenge with Taenia crassiceps cysts when mice are immunized with recombinant fragments of TPmy. Initial protection studies using genetic immunization showed that amino terminal end fragment of TPmy cloned into a plasmid expression vector with a cytomegalovirus promoter, together with IL-12-expressing plasmids induced 79% protection, suggesting that this kind of TPmy-immunization might result in development of a cost-effective vaccine against cysticercosis.