HUMAN RARE SEROTYPE ADENOVIRUS AS VACCINE PLATFORM AGAINST T. cruzi INFECTION

TRINITARIO SN; DELFINO MA; REDOLFI DM; RUSSO M; CARDOSO AC; CERNY N; BIVONA AE; MALCHIODI EL; SÁNCHEZ ALBERTI A

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

Trypanosoma cruzi is an obligate intracellular parasite and stealthinvader that causes a chronic infection affecting millions of peopleworldwide. Benznidazole, the first line antiparasitic drug, has beenused for 50 years and is effective during the acute phase of the infection.However, its use in chronic phase where most cases are diagnosed,is still controversial. Considering these issues developingprophylactic and/or therapeutic vaccines might contribute to publichealth.In this context, our laboratory has developed Traspain, a novel chimericantigen that displays key domains for humoral and cytotoxicanti-parasite immune response. In order to improve antigen-specificcell-mediated immunity, we designed a low-seroprevalence recombinantadenoviral vector (Ad48) carrying Traspain gene.METHODSTraspain gene was fused to mouse immunoglobulin Kappa lightchain signal peptide DNA sequence (SPTrasp) to facilitate extracellularantigen export upon vaccination. Adenovirus 48 carryingSPTrasp gene (Ad48-SPTrasp) was generated using traditional cloning and homologous recombination in HEK293 cells. Antigenexpression was assessed in-vitro by RT-PCR and Western blot.Exploratory immunization experiments were carried out in C57/BL6mice, administering two subcutaneous doses of Ad48-SPTrasp every15 days.RESULTSWe were able to rescue the replication deficient virus and detectantigen expression upon 48 hours of in-vitro infection. Vaccinatedanimals developed anti-Traspain antibodies (immunized vs controlanimals ELISA titers: 1782 and 235 respectively) and isotype determinationindicated an IgG1/IgG2a ratio of 3.4. Robust antigen-specificCTL response was detected using tetramer staining (CD8+VNHRLTVL+ cells, immunized: 3.5 % vs control: 0.6 %, p