Alphavirus replicon DNA encoding Traspain showed immunogenicity and efficacy as vaccine candidate against T. cruzi infection

DELFINO MARIA ALICIA; TRINITARIO, SEBASTIÁN NICOLÁS; DZVONIK POLINA; BIVONA, AUGUSTO ERNESTO; CARDOSO LADANBURU ALEJANDRO; TARLETON RICK L; MALCHIODI, EMILIO LUIS; SANCHEZ ALBERTI ANDRES

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias 2022; 2022

Chagas disease, caused by Trypanosoma cruzi, is parasitic diseasethat affect 6-7 million people worldwide. Treatment is limitedto the acute phase and there is not approved vaccine. Nucleic acid-based vaccines are strong type I response inducers, effective tocontrol intracellular pathogens infection. Previously, we developeda DNA-launched RNA replicon encoding Traspain, a chimeric T.cruzi antigen (DREP-Tp). Here, we determined humoral and cellularimmune response, and efficacy in a murine model. Semliki Forestvirus based DREP was constructed employing a quality by designapproach, applying DNA assembly tools. Its identity was confirmedby sequencing and restriction analysis. Antigen expression wasdetected by Western blot in transfected cells. To evaluate its immunogenicity,groups of C3H female mice were vaccinated by theintramuscular route with 3 doses of either 10 μg, 100 μg or 250μg of naked DREP-Tp. Placebo group received PBS and a referencegroup was immunized with 3 doses of 10 μg of recombinantTraspain combined with 50 μg of cyclic-di-AMP adjuvant (Tp-CDA).Higher specific antibody titers were detected in Tp-CDA vs DREPTpgroups (IgG titers: 64834 vs <400). The latter, conversely,showed an increased expansion of epitope-specific CD8+ T cellsat endpoint (%CD8+CD44highTEWETGQI+ 1.16 vs 2.37, Tp-CDA andDREP-Tp 250 μg respectively). Memory phenotype of this subset atearly 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 withthe RA strain of T. cruzi (DTU VI). All DREP-Tp groups showed asignificant 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 results strongly suggestthe utility of SFV-DREP encoding Traspain as potential vaccineagainst T. cruzi.