DNA-LAUNCHED RNA REPLICON AS A NOVEL VACCINE PLATFORM AGAINST TRYPANOSOMA CRUZI INFECTION

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

Simposio; Keystone Symposia: Progress in Vaccine Development for Infectious Diseases; 2022

Chagas disease is a potentiallylife-threatening illness caused by the protozoan intracellular parasite Trypanosoma cruzi. About 6 million peopleworldwide are estimated to be infected. Currently there is no vaccine andtreatment is limited to the acute phase.Nucleic acid-based vaccines are strongtype I response inducers, effective to control intracellular pathogensinfection. Here, we developed a DNA-launched RNA replicon encoding Traspain, achimeric T.cruzi antigen (DREP-Tp) and assessed its immunogenicity in amurine model.SemlikiForest virus based DREP was constructed employing a quality by design approach,applying DNA assembly tools. Its identity was confirmed by sequencing andrestriction analysis. Antigen expression was detected by Western blot intransfected cells. To evaluate its immunogenicity, groups of C3H female micewere vaccinated by the intramuscular route with 3 doses of either 10 ug, 100 ugor 250 ug of naked DREP-Tp. Placebo group received PBS and a reference groupwas immunized with 3 doses of 10 ug of recombinant Traspain combined with 50 ugof cyclic-di-AMP adjuvant (Tp-CDA).Higherspecific antibody titers were detected in Tp-CDA vs DREP-Tp groups (IgG titers:64834 vs <400). The latter, conversely, showed anincreased expansion of epitope-specific CD8+ T cells at endpoint (%CD8+CD44highTEWETGQI+1.16 vs 2.37, Tp-CDA and DREP-Tp 250ug 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. CD4+ IL-17+T cells were detected in lymph nodes from all vaccinated mice [(0.96*; 0.97*; 0.86*;0.69 vs 0.28%, DREP-Tp 10ug, 100ug, 250ug and Tp-CDArespectively vs placebo (*p<0.05)]. Increased proliferation of spleencells was observed in higher doses of DREP-Tp groups vs placebo (PI: 6.5-11.6-14.3vs 6).Future experimentswill be focused on the evaluation of DREP-Tp efficacy as an anti-T.cruzivaccine in the murine model. In conclusion, this work highlights the utility ofthe SFV-DREP platform as a tool to assess immunogenicity of novel T. cruziantigens.