Human rare serotype adenovirus as vaccine platform against T. cruzi infection

TRINITARIO, SEBASTIÁN NICOLÁS; MARIA ALICIA DELFINO; ALEJANDRO C CARDOSO LANDABURU; MELISSA RUSSO; NATACHA CERNY; AUGUSTO E BIVONA; EMILIO L MALCHIODI; SANCHEZ ALBERTI ANDRES

Congreso; Reunión Anual de Sociedades de Biociencias 2020; 2020

BACKGROUND.Trypanosomacruzi is an obligate intracellular parasite and stealth invader that causes achronic infectionaffecting millions of people worldwide. Benznidazole, thefirst line anti parasitic drug, has been used for 50 years and is effectiveduring the acute phase of the infection. However, its use in chronic phasewhere most cases are diagnosed, is still controversial. Considering theseissues developing prophylactic and/or therapeutic vaccines might contribute topublic health.In this context, our laboratory has developed Traspain, a novelchimeric antigen that displays key domains for humoral and cytotoxicanti-parasite immune response. In order to improve antigen-specific cell-mediatedimmunity, we designed a low-seroprevalence recombinant adenoviralvector (Ad48)carrying Traspain gene. METHODS.Traspain gene was fused to mouse immunoglobulinKappa light chain signal peptide DNAsequence (SPTrasp) to facilitateextracellular antigen export upon vaccination.Adenovirus 48 carrying SPTraspgene (Ad48-SPTrasp) was generated using traditional cloning and homologousrecombination in HEK293 cells. Antigen expression was assessed in-vitrobyRT-PCR and Western blot. Exploratory immunization experiments were carriedout in C57/BL6 mice, administering two subcutaneous doses of Ad48-SPTrasp every15days.RESULTS. We were able to rescue the replication deficient virus anddetect antigen expression upon 48 hours of in-vitro infection. Vaccinatedanimals developed anti-Traspain antibodies (immunized vs control animals ELISAtiters: 1782 and 235respectively) and isotype determination indicated anIgG1/IgG2a ratio of 3.4.Robust antigen-specific CTL response was detected usingtetramer staining (CD8+VNHRLTVL+ cells, immunized: 3.5 % vs control: 0.6 %,p<0.01). CONCLUSIONS. Considering these results, Ad48-SPTrasp appearsas ahigh potential approach for improving the current strategies ofvaccine-mediatedcontrol of T. cruzi.