TcTASV antigens delivered in baculovirus confer protection against Trypanosoma cruzi infection, notably reducing levels of circulating trypomastigotes, parasite tissue load and mortality.

MASIP, Y; MOLINA, G; CAEIRO, L; MOLINARI, MP; TEKIEL, V.

virtual

Congreso; XXXI Molecular Parasitology Meeting; 2020

MPM

TcTASV ANTIGENS DELIVERED IN BACULOVIRUS CONFER PROTECTION AGAINST TRYPANOSOMA CRUZI INFECTION, NOTABLY REDUCING LEVELS OF CIRCULATING TRYPOMASTIGOTES, PARASITE TISSUE LOAD AND MORTALITYYAMIL E. MASIP1, GUIDO MOLINA2, LUCAS D. CAEIRO1,3, MARÍA P. MOLINARI2,3 AND VALERIA TEKIEL1,31 Instituto de Investigaciones Biotecnológicas "R.Ugalde" (IIBIO), Universidad Nacional de San Martín, Argentina; 2 Laboratorio de Baculovirus, Instituto de Biotecnología, INTA, Argentina; 3 Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), ArgentinaTcTASV is a medium size multigenic family unique to Trypanosoma cruzi present in all strains of the parasite and expressed in the life cycle stages of the mammalian host. Subfamilies TcTASV-A and TcTASV-C are the most numerous, are in contact with the host immune system and show differential expression patterns: TcTASV-A is expressed intracellularly in amastigotes and trypomastigotes while TcTASV-C is expressed at trypomastigote surface and secreted (Garcia et al, 2010; Bernabó et al, 2013; Floridia et al, 2016, 2019). Previous vaccination assays with TcTASV-C resulted in delayed appearance of bloodstream trypomastigotes but impacted only slightly in mortality, after challenge with RA (TcVI), a highly virulent T. cruzi strain. The immune response was essentially humoral, with negligible cellular response (Caeiro et al, 2018). We hypothesized that a vaccination protocol with TcTASV could be improved by triggering also a cellular response against TcTASV-A (intracellular antigen). As heterologous antigen displayed at baculovirus (BV) capsid has been reported to induce cellular responses, we engineered a recombinant BV that accurate express TcTASV-A (BV-TcTASV-A) fused to VP39, the major nucleocapsid protein. Mice were first immunized with rTcTASV-C adjuvanted with aluminum hydroxide, followed by a boost with BV-TcTASV-A plus rTcTASV-C. This immunization scheme induced a strong anti-TcTASV-C humoral response along with CD8+/IFNγ+ (5,2%) and CD4+/IFNγ+ (0,7%) T cell populations after restimulation with TcTASV-A and TcTASV-C, respectively. When challenged with RA strain, BV-TcTASV immunized mice presented lower levels of circulating trypomastigotes and 95% survival (vs 60% BVwt and 0% PBS). Additionally, we evaluated tissue damage on day 75 p.i., as a model of chronic infection. Samples of heart, skeletal muscle and spleen, presented a notable decrease in the relative levels of parasites in tissues (98.5% decrease compared to PBS; qPCR). We conclude that this immunization protocol elicited a robust immune response against TcTASV family, which could be relevant in protection against T. cruzi.Funding: ANPCyT PICT 2016-0108. Argentina.