SHIFT IN THE HUMORAL RESPONSE ELICITED BY Trypanosoma cruzi ATTENUATED PARASITES WHEN COADMINISTERED WITH A PLASMID ENCODING MURINE IFN-GAMMA

CECILIA PEREZ BRANDAN; ANDREA C. MESIAS; RUBEN CIMINO; PATRICIO DIOSQUE; MIGUEL ANGEL BASOMBRIO

Santa Fe

Exposición; XXVIII Reunión Anual de la Sociedad Argentina de Protozoología y Enfermedades Parasitarias; 2016

Sociedad Argentina de Protozoologia

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 1 response able to control intracellular parasites. Therefore, the aim of the present study was to test whether the co-administration of a plasmid encoding IFN-γ could improve the well proven highly protection gain through vaccination with live attenuated parasites. For this purpose C57BL/6J mice were immunized with three doses of live metacyclic parasites in combination with plasmid pVXVR-mIFN. The immunization regimens were done intraperitoneally every 4 weeks. Sera levels of T. cruzi-specific IgGs, determined by an ELISA, were detectable after the 1st immunization dose in the group of mice in which pVXVR-mIFN was administered in combination with TCC attenuated parasites. Even more the antibody levels increased significantly after the second dose. IgG1 were primarily detected in TCC-immunized animals with significantly low predominance of IgG2a antibodies; however when pVXVR-mIFN is administered a balance between IgG1 and IgG2a is almost reached. These results indicate that the addition of a plasmid encoding murine IFN elicited an enhanced parasite-specific humoral response capable of redirecting the Th2-type phenotype obtained by the immunization with TCC attenuated parasites towards a Th1-type. To analyze if the immune response elicited by the administration of IFN- in conjunction with live attenuated parasites protects against a future infection, all experimental groups were submitted to a lethal challenge with virulent bloodstream tripomastigotes. A significant reduction in parasite load was observed in all groups immunized with live attenuated parasites as expected; however, in the group of mice in which pVXVR-mIFN was also 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.