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

TRINITARIO, SEBASTIÁN NICOLÁS; DELFINO, MARÍA ALICIA; REDOLFI, DANIELA; RUSSO, MELISSA; CARDOSO LANDABURU, ALEJANDRO; CERNY, NATACHA; BIVONA, AUGUSTO ERNESTO; MALCHIODI, EMILIO LUIS; SANCHEZ ALBERTI, ANDRÉS

Buenos Aires

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIAS SAIC - SAI - SAFIS; 2020

Sociedad Argentina de Inmunología (SAI)

BACKGROUNDTrypanosoma cruzi is an obligate intracellular parasite and stealth invader thatcauses a chronic infection affecting millions of people worldwide. Benznidazole, thefirst line antiparasitic drug, has been used for 50 years and is effective during theacute phase of the infection. However, its use in chronic phase where most casesare diagnosed, is still controversial. Considering these issues developingprophylactic and/or therapeutic vaccines might contribute to public health.In this context, our laboratory has developed Traspain, a novel chimeric antigen thatdisplays key domains for humoral and cytotoxic anti-parasite immune response. Inorder to improve antigen-specific cell-mediated immunity, we designed a lowseroprevalence recombinant adenoviral vector (Ad48) carrying Traspain gene.METHODSTraspain gene was fused to mouse immunoglobulin Kappa light chain signal peptideDNA sequence (SPTrasp) to facilitate extracellular antigen export upon vaccination.Adenovirus 48 carrying SPTrasp gene (Ad48-SPTrasp) was generated usingtraditional cloning and homologous recombination in HEK293 cells. Antigenexpression was assessed in-vitro by RT-PCR and Western blot. Exploratoryimmunization experiments were carried out in C57/BL6 mice, administering twosubcutaneous doses of Ad48-SPTrasp every 15 days.RESULTSWe were able to rescue the replication deficient virus and detect antigen expressionupon 48 hours of in-vitro infection. Vaccinated animals developed anti-Traspainantibodies (immunized vs control animals ELISA titers: 1782 and 235 respectively)and isotype determination indicated an IgG1/IgG2a ratio of 3.4. Robust antigenspecific CTL response was detected using tetramer staining (CD8+ VNHRLTVL+cells, immunized: 3.5 % vs control: 0.6 %, p