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

DELFINO, MARÍA ALICIA; TRINITARIO, SEBASTIÁN NICOLÁS; DZVONYK, POLINA; CERNY, NATACHA; CARDOSO LANDABURU, ALEJANDRO; TARLETON, RICK L.; BIVONA, AUGUSTO ERNESTO; MALCHIODI, EMILIO LUIS; SANCHEZ ALBERTI, ANDRÉS

Mar del Plata

Congreso; LXX Reunión Anual de la Sociedad Argentina de Inmunología (SAI); 2022

Chagas disease, caused by Trypanosoma cruzi, is parasitic diseasethat affect 6-7 million people worldwide. Treatment is limited to theacute phase and there is not approved vaccine. Nucleic acid-basedvaccines are strong type I response inducers, effective to controlintracellular pathogens infection. Previously, we developed a DNAlaunchedRNA replicon encoding Traspain, a chimeric T. cruzi antigen(DREP-Tp). Here, we determined humoral and cellular immuneresponse, and efficacy in a murine model.Semliki Forest virus based DREP was constructed employing aquality by design approach, applying DNA assembly tools. Its identitywas confirmed by sequencing and restriction analysis. Antigen expressionwas detected by Western blot in transfected cells. To evaluateits immunogenicity, groups of C3H female mice were vaccinatedby the intramuscular route with 3 doses of either 10 μg, 100 μg or250 μg 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