ALPHAVIRUS REPLICON DNA ENCODING TRASPAIN SHOWED IMMUNOGENICITY AND EFFICACY AS VACCINE CANDIDATE AGAINST T. CRUZI INFECTION

TRINITARIO SN; BIVONA AE; MALCHIODI EL; DELFINO MA; CERNY N; TARLETON RL; DZVONYK P; CARDOSO A; SÁNCHEZ ALBERTI A

Congreso; Reunión Anual de Sociedades de Biociencias SAIC. SAI & FAIC. SAFIS; 2022

Chagasdisease, caused by Trypanosoma cruzi, is a parasitic disease that affect6-7 million people worldwide. Treatment is limited to the acute phase and thereis not approved vaccine. Nucleic acid-based vaccines are strong type I responseinducers, effective to control intracellular pathogens infection. Previously,we developed a DNA-launched RNA replicon encoding Traspain, a chimeric T. cruziantigen (DREP-Tp). Here, we determined humoral and cellular immune response, and efficacy in a murine model.Semliki Forest virus based DREP wasconstructed employing a quality by design approach, applying DNA assemblytools. Its identity was confirmed by sequencing and restriction analysis.Antigen expression was detected by Western blot in transfected cells. Toevaluate its immunogenicity, groups of C3H female mice were vaccinated by theintramuscular route with 3 doses of either 10 µg, 100 µg or 250 µg of nakedDREP-Tp. Placebo group received PBS and a reference group was immunized with 3doses of 10 µg of recombinant Traspain combined with 50 µg of cyclic-di-AMPadjuvant (Tp-CDA).Higher specific antibody titers were detectedin Tp-CDA vs DREP-Tp groups (IgG titers: 64834 vs <400). Thelatter, conversely, showed an increased expansion of epitope-specific CD8+T cells at endpoint (%CD8+CD44highTEWETGQI+ 1.16vs 2.37, Tp-CDA and DREP-Tp 250 µg respectively). Memory phenotype of thissubset at early time-point showed a predominance of effector vs central andeffector memory T cells in DREP-Tp groups compared to Tp-CDA.To evaluate vaccine efficacy,immunized mice were challenged with the RA strain of T. cruzi (DTU VI).All DREP-Tp groups showed a significant parasitemia reduction vs placebo [(AUC:25.7**, 18.7****,26.2** vs 44.2,DREP-Tp 10 µg, 100 µg and 250 µg vs placebo (**p<0.005 ****p<0.0001)].In conclusion, these resultsstrongly suggest the utility of SFV-DREP encoding Traspain as potential vaccineagainst T. cruzi.