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

MARIA ALICIA DELFINO; TRINITARIO, SEBASTIÁN N.; MELISSA RUSSO; ALEJANDRO C CARDOSO LANDABURU; CERNY, NATACHA; EMILIO L MALCHIODI; AUGUSTO E BIVONA; ANDRES SANCHEZ ALBERTI

Congreso; V International Congress in Translational Medicine; 2021

FFYB-UBA

BACKGROUND AND AIMSChagas Disease is a potentiallylife-threatening illness caused by the protozoan parasite Trypanosoma cruzi.WHO recognize it as a neglected tropical disease, which affects 6-7 millionpeople in Latin America. After 100 years of its discovery, no effective vaccineto prevent 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 the protectionagainst the parasite, we evaluate 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 plus25 µg of Poly (I:C) in sterile PBS or only buffer as placebo. Exploratorybleeding was performed and 20-30 days after the last dose mice antigen specificimmune responses were evaluated by ELISA, proliferation and flowcytometry.  Alternatively, for efficacyassessment, vaccinated mice were challenged with a lethal dose of T. cruzi RAstrain (DTU VI). Parasitemia, weight loss and survival were employed as readouts.  RESULTS: Traspain-specific IgG titres were detectedafter the 2nd dose and peaked significantly after the 3rd dose ofTraspain/Poly(I:C) in vaccinated mice.Robust antigen-specific responses were detectedin vivo 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 showedproduction of IL-2, TNFα and IFN on the CD4+ subset upon protein recall.Boolean gate analysis revealed that nearly 65% of the cytokine producing CD4+ Tcells correspond to polyfunctional subsets, highlighting the utility of thisadjuvant. Systemic CD8+ T cell responses were detected byin-vivo CTL assays (18% specific Lysis of TEWETGQI loaded spleen cells) forvaccinated animals. Vaccinated animals were able to reduce parasitemia (2-folddecrease in area under the parasitemia curve vs control, p<0.05) and lowerweight loss however survival rates were not improved vs control group. CONCLUSIONSTraspain combined with a TLR3 agonistadministered by the subcutaneous route is immunogenic and confers partialprotection that needs to be improved for new vaccine development against T.cruzi.