TRASPAIN FORMULATED WITH THE TLR3-AGONIST POLY (I:C) IS IMMUNOGENIC AND CONFERS PARTIAL PROTECTION AGAINST T. CRUZI. INFECTION

DELFINO MARÍA ALICIA; TRINITARIO SEBASTIAN N; RUSSO MELISSA; CARDOSO ALEJANDRO; CERNY NATACHA; MALCHIODI EMILIO L; BIVONA AUGUSTO E; SÁNCHEZ ALBERTI ANDRÉS

Congreso; V International Congress in Translational Medicine; 2021

International Master Program in Biomedical Sciences (IMBS)

BACKGROUND AND AIMS:Chagas Disease is a potentially life-threateningillness caused by the protozoan parasite Trypanosoma cruzi. WHOrecognize it as a neglected tropical disease, which affects 6-7 million peoplein Latin America. After 100 years of its discovery, no effective vaccine toprevent or treat the infection is available. We have previously developedTraspain, a chimeric trivalent immunogen that proved effective as aprophylactic vaccine. To assess new adjuvants that might improve protectionagainst the parasite, we evaluated the TLR3 ligand Poly (I:C) by thesubcutaneous route.  METHODS: Groups of 6-8 weeks old, Female C3H mice (n=6/group)were vaccinated with 3 doses of 10 µg of recombinant Traspain plus 25 µg ofPoly (I:C) in sterile PBS or only buffer as placebo. Exploratory bleeding wasperformed and 20-30 days after the last dose mice antigen specific immune responseswere evaluated by ELISA, proliferation and flow cytometry.  Alternatively, for efficacy assessment,vaccinated mice were challenged with a lethal dose of T. cruzi RA strain(DTU VI). Parasitemia, weight loss and survival were employed as readouts.   RESULTS: Traspain-specific IgG titres were detected after the 2nddose and peaked significantly after the 3rd dose of Traspain/Poly(I:C)in vaccinated mice.Robust antigen-specific responses were detected invivo by delay type hypersensitivity assay and ex-vivo by proliferationassays (Proliferation index vaccinated vs placebo: 17 vs 4, p<0.001).Spleen cells from vaccinated animals showed productionof IL-2, TNFα and IFNg on the CD4+subset upon protein recall. Boolean gate analysis revealed that nearly 65% ofthe cytokine producing CD4+ T cells correspond to polyfunctional subsets,highlighting the utility of this adjuvant. Systemic CD8+ T cell responses were detected by in-vivoCTL assays (18% specific Lysis of TEWETGQI loaded spleen cells) for vaccinatedanimals. Vaccinated animals were able to reduce parasitemia (2-fold decrease inarea under the parasitemia curve vs control, p<0.05) and lower weight losshowever survival rates were not improved vs control group.  CONCLUSIONS:Traspain combined with a TLR3 agonist administered bythe subcutaneous route is immunogenic and confers partial protection that needsto be improved for new vaccine development against T. cruzi.