DNA-LAUNCHED RNA REPLICON VACCINE CANDIDATE EXHIBITED IMMUNOGENICITY AND EFFICACY AGAINST TRYPANOSOMA CRUZI INFECTION

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

Congreso; International Society for Vaccines Annual Congress; 2023

Chagas disease is a potentially life-threatening illness caused by the protozoan intracellular parasite Trypanosoma cruzi. More than 6 million people worldwide are estimated to be infected. Currently there is no vaccine available, and treatment is limited mainly to the acute phase.Nucleic acid-based vaccines are strong type I response inducers, effective to control intracellular pathogens infection. DNA-launched RNA replicons (DREP) have demonstrated superior immunogenicity over traditional DNA vaccines. In this study, we developed a DREP encoding Traspain, a chimeric T.cruzi antigen (DREP-Tp) and assessed its immunogenicity and efficacy in a murine model.Alphavirus based DREP was constructed combining quality by design and DNA assembly tools. Its identity was confirmed by sequencing and restriction analysis. Antigen expression was verified by western blot and flow cytometry in transfected cells.To evaluate its immunogenicity, groups of C3H female mice were vaccinated 3 times by the intramuscular route with a low, medium or high dose of naked DREP-Tp. A reference group was immunized with 3 doses of 10 ug of recombinant Traspain combined with 50 ug of cyclic-di-AMP adjuvant (Tp-CDA) and placebo group received buffer saline.Higher specific antibody titers were detected in Tp-CDA vs DREP-Tp groups (IgG titers: 64834 vs