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

MASIP, YAMIL E.; MOLINA, GUIDO; CAEIRO, LUCAS D.; MOLINARI, MARÍA P.; TEKIEL, VALERIA

Massachusetts

Congreso; XXXI Molecular Parasitology Meeting; 2020

Genetics Society of America

TcTASV 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.