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

TRINITARIO SN; DELFINO MA; BIVONA AE; REDOLFI DM; RUSSO M; CARDOSO, AC.; CERNY N; BIVONA AE; MALCHIODI EL; SANCHEZ ALVERTI A

Congreso; Reunion de Sociedades de Biociencias; 2020

Sociedad Argentina de Inmunología

Trypanosoma cruzi is an obligate intracellular parasite and stealth invader that causes a chronic infection affecting millions of people worldwide. Benznidazole, the first line antiparasitic drug, has been used 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 developing prophylactic and/or therapeutic vaccines might contribute to public health. In this context, our laboratory has developed Traspain, a novel chimeric antigen that displays key domains for humoral and cytotoxic anti-parasite immune response. In order to improve antigen-specific cell-mediated immunity, we designed a low-seroprevalence recombinant adenoviral vector (Ad48) carrying Traspain gene.METHODSTraspain gene was fused to mouse immunoglobulin Kappa light chain signal peptide DNA sequence (SPTrasp) to facilitate extracellular antigen 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/BL6 mice, administering two subcutaneous doses of Ad48-SPTrasp every 15 days.RESULTSWe were able to rescue the replication deficient virus and detect antigen expression upon 48 hours of in-vitro infection. Vaccinated animals developed anti-Traspain antibodies (immunized vs controlanimals ELISA titers: 1782 and 235 respectively) and isotype determination indicated and IgG1/IgG2a ratio of 3.4. Robust antigen-specific CTL response was detected using tetramer staining (CD8+VNHRLTVL+ cells, immunized: 3.5 % vs control: 0.6 %, p