TRASPAIN DELIVERED BY ADENOVIRAL VECTOR AS VACCINE AGAINST TRYPANOSOMA CRUZI

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

Buenos Aires

Congreso; V International Congress in Translational Medicine; 2021

BACKGROUND AND AIMSTrypanosoma cruzi is an obligate intracellular parasite and stealth invader that causes a chronic infection affecting millions of people worldwide. There is no vaccine against T. cruzi infection. Benznidazole, the first line antiparasitic drug, has been used for 50 years and is effective during the acute phase of the infection, but its use in chronic phase, where most cases are diagnosed, is still controversial. Considering these issues developing prophylactic and/or therapeutic vaccines is of utmost importance.In this context, our laboratory has developed Traspain, a chimeric antigen that displays key domains for humoral and cytotoxic anti-parasite immune response. To enhance the antigen-specific cell-mediated immunity, we have chosen one of the latest vaccine platforms approved for clinical use, Adenoviral vectors. Here we will present the design and development of a low-seroprevalence recombinant adenoviral vector (adenovirus 48) carrying Traspain gene, its preliminary performance as immunogenic antigen and the cross reactivity with the most prevalent serotype (adenovirus 5).METHODSTraspain gene was fused to mouse immunoglobulin Kappa light chain signal peptide DNA sequence (SPTrasp) to facilitate extracellular antigen export upon vaccination. Adenovirus 48 carrying SPTrasp gene (Ad48-SPTrasp) was generated using traditional cloning and homologous recombination in HEK293 cells. Antigen expression was assessed in-vitro by RT-PCR and Western blot. Exploratory immunization experiments were carried out in C57BL/6 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 control animals ELISA titers: 1782 and 235 respectively). Isotype determination indicated an IgG1/IgG2a ratio of 3.4. Robust antigen-specific CTL response was detected in blood of vaccinated animals using tetramer staining (%CD8+ H-2Kb VNHRFTLV+ cells, immunized: 3.5 % vs control: 0.6 %, p