Shift in the humoral response elicited by Trypanosoma cruzi attenuated parasites when coadministered with a plasmid encoding murene IFN-Gamma

PEREZ BRANDAN C; MESIAS AC; CIMINO, RO; DIOSQUE, P; BASOMBRIO, MA

Santa Fe

Simposio; XXVIII Reunión Anual de la Sociedad Argentina de Protozoología y Enfermedades Parasitarias - SIMPOSIO Internacional de Biología Celular y Molecular de la Enfermedad de Chagas; 2016

Sociedad Argentina de Protozoología

In Trypanosoma cruzi infection it is known that early interferon-gamma (IFN-γ) release by cells of the innate immune system is critical to lead type 1response able to control intracellular parasites. Therefore, the aim of the present study was to test whether the co-administration of a plasmidencoding IFN-γ could improve the well proven high protection obtained through vaccination with live attenuated parasites belonging to TCC strain.For this purpose C57BL/6J mice were immunized with three doses of live metacyclic TCC parasites in combination with plasmid pVXVR-mIFN-γ. Theimmunization regimens were done intraperitoneally every 4 weeks. Sera levels of T. cruzi-specific IgGs were evaluated by ELISA. After the 1st immunization dose specific IgGs were detectable in the group of mice in which pVXVRmIFN-γ was administered in combination with TCC attenuated parasites and the antibody levels increased significantly after the second dose. IgG1 were primarily Detected in TCC-immunized animals with significantly low predominance ofIgG2a antibodies; however when pVXVR-mIFN=γ is administered a balance between IgG1 and IgG2a is almost reached. These results indicate that the addition of a plasmid encoding murine IFN-γ elicited an enhanced parasite-specifichumoral response capable of redirecting the Th2-type phenotype obtained by the immunization with TCC attenuated parasites towards a Th1-type. Toanalyze if the immune response elicited by the administration of IFN-γ in conjunction with live attenuated parasites protects against a futureinfection, all experimental groups were submitted to a lethal challenge with virulent bloodstream tripomastigotes. A significant reduction in parasiteload was observed in all groups immunized with live attenuated parasites as expected; however, in the group of mice in which pVXVR-mIFN-γ wasalso administered a reduction even more noticeable was detected. These results support the idea of generating a multicomponent vaccine based on live attenuated parasites. This work is funded by Agencia Nacional de Promoción Científica y Técnica.