TRASPAIN DELIVERED BY ADENOVIRAL VECTOR AS VACCINE AGAINST TRYPANOSOMA CRUZI

TRINITARIO SEBASTIAN N; DELFINO MARÍA ALICIA; DZVONYK POLINA; RUSSO MELISSA; CARDOSO ALEJANDRO; CERNY NATACHA; BIVONA AUGUSTO E; MALCHIODI EMILIO L; SÁNCHEZ ALBERTI ANDRÉS

Congreso; V International Congress in Translational Medicine; 2021

International Master Program in Biomedical Sciences (IMBS)

BACKGROUND AND AIMSTrypanosoma cruzi is an obligateintracellular parasite and stealth invader that causes a chronic infectionaffecting millions of people worldwide. There is no vaccine against T. cruziinfection. Benznidazole, the first line antiparasitic drug, has been used for50 years and is effective during the acute phase of the infection, but its usein chronic phase, where most cases are diagnosed, is still controversial.Considering these issues developing prophylactic and/or therapeutic vaccines isof utmost importance.In this context, our laboratory has developed Traspain, a chimeric antigen thatdisplays key domains for humoral and cytotoxic anti-parasite immune response. Toenhance the antigen-specific cell-mediated immunity, we have chosen one of thelatest vaccine platforms approved for clinical use, Adenoviral vectors. Here wewill present the design and development of a low-seroprevalence recombinantadenoviral vector (adenovirus 48) carrying Traspain gene, its preliminaryperformance as immunogenic antigen and the cross reactivity with the mostprevalent serotype (adenovirus 5).METHODSTraspain gene was fused to mouse immunoglobulin Kappa light chain signal peptide DNA sequence (SPTrasp) tofacilitate extracellular antigen export upon vaccination. Adenovirus 48carrying SPTrasp gene (Ad48-SPTrasp) was generated using traditional cloningand 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 antigenexpression upon 48 hours of in-vitroinfection. Vaccinated animals developed anti-Traspain antibodies (immunized vscontrol animals ELISA titers: 1782 and 235 respectively). Isotype determinationindicated an IgG1/IgG2a ratio of 3.4. Robust antigen-specific CTL response wasdetected in blood of vaccinated animals using tetramer staining (%CD8+ H-2KbVNHRFTLV+ cells, immunized: 3.5 % vs control: 0.6 %, p<0.01). Crossreactivity analysis of the humoral immune response revealed that Ad48-SPTraspwas not recognized by Ad5 immunized mice serum in Western blot assays.CONCLUSIONSConsidering these results, Ad48-SPTrasp appears as a high potential approachfor improving the current strategies of vaccine development against T. cruzi.