The trypomastigote surface protein TCTASV-C induces partial protection against Trypanosoma cruzi in mice.

CAEIRO, LUCAS; ALBA SOTO, CATALINA D; SANCHEZ, DANIEL O.; TEKIEL, VALERIA

Mar del Plata

Congreso; X Congreso de Protozoología y enfermedades parasitarias; 2014

Sociedad Argentina de Protozoología

TcTASV is an Alanine, Serine and Valine-rich protein family, initially identified by our group from a cDNA library of trypomastigote-enriched mRNAs. TcTASV family consists of ~40 members, is present in T. cruzi strains from different lineages and has no orthologs in other trypanosomatids. All members of the TcTASV family have conserved coding aminoand carboxy-termini, and a central variable core that allows partitioning of TcTASV proteins into three subfamilies, A, B and C. We showed that TcTASV-C is preferentially expressed in trypomastigotes and is highly phosphorylated and glycosylated. TcTASV-C is anchored to the trypomastigote?s membrane by a GPI anchor, is spontaneously released to the medium and is localized in discrete spots or patches on cell membrane and flagellum of trypomastigotes. Furthermore, approximately 30% of sera from infected host (experimental animals and humans) were reactive with TcTASV-C, confirming its expression in the natural cycle of the parasite. Preliminary results suggest that it may also be good vaccine candidate. In this project, we studied TcTASV-C to analyze its protective capacity against T. cruzi. We employed a prime and boost vaccination schedule (2 doses of DNA + GM-CSF/mouse and 2 doses of protein + alum/ mouse; TcTASV-C: n=10; controls: n=10). Fifteen days after the last dose, sera were obtained to test antibody response, in which we observed a significant response Th1/Th2 against TcTASV-C, and animals were challenged with the highly virulent T. cruzi RA strain (lineage VI). Vaccinated animals presented a delay in the appearance of detectable parasites in blood, and a significant higher survival rate in vaccinated mice than controls (100% vs 30% at 30 d.p.i.), suggesting that TcTASV-C induces a partially protective response and is a good vaccine candidate that deserves further studies.