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

DELFINO MA; TRINITARIO SN; RUSSO M; CARDOSO AC; CERNY N; EMILIO L MALCHIODI; BIVONA AE; SANCHEZ ALVERTI A

Congreso; Reunión Conjunta SAIC- SAI- AAFE; 2021

Sociedad Argentina de Inmunologia

PRIZE: BACKGROUND AND AIMS:Chagas Disease is a potentially life-threatening illness caused by the protozoan parasite Trypanosoma cruzi. WHO recognize it as a neglected tropical disease, which affects 6-7 million people in Latin America. After 100 years of its discovery, no effective vaccine to prevent or treat the infection is available. We have previously developed Traspain, a chimeric trivalent immunogen that proved effective as a prophylactic vaccine. To assess new adjuvants that might improve protection against the parasite, we evaluated the TLR3 ligand Poly (I:C) by the subcutaneous 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 of Poly (I:C) in sterile PBS or only buffer as placebo. Exploratory bleeding was performed and 20-30 days after the last dose mice antigen specific immune responses were 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 2nd dose and peaked significantly after the 3rd dose of Traspain/Poly(I:C) in vaccinated mice.Robust antigen-specific responses were detected in vivo by delay type hypersensitivity assay and ex-vivo by proliferation assays (Proliferation index vaccinated vs placebo: 17 vs 4, p