Chagas Disease vaccine based on antigen engineering and Sting Agonist

SANCHEZ ALBERTI ANDRES; AUGUSTO E BIVONA; NATACHA CERNY; ALEJANDRO C CARDOSO LANDABURU; SCHULZE, KAI; WEIßMANN, S; EBENSEN, T; PADILLA ANGEL; TARLETON RICK L; CARLOS A. GUZMÁN; SILVIA I CAZORLA; MALCHIODI E

Congreso; LASID-SAI; 2015

Background: Chagas Disease, is a potentially life-threatening illness cause by the protozoan parasite Trypanosoma cruzi. WHO recognize it as a neglected tropical disease, which affects 12 million people in Latin America. After 100 years of its discovery, no effective vaccine to prevent or treat the infection is approved. Methods: Recombinant(r) Traspain, a trivalent immunogen was rationally designed based on the structural signature and immunogenic ability of each component. Novel adjuvants, as STING Agonists were employed in combination with rProtein or DNA-prime+rProtein-boost in vaccination protocols in C3H or C57/BL6 mice. Wt or Td-tomato expressing parasites were employed for challenge. Results: Antibodies raised against rTraspain blocked in-vitro infection (60% vs. preimmune serum). ELISPOT assay showed a balanced TH1/TH2/TH17 profile for immunized groups. An expansion of pathogen specific CD8+ T lymphocytes comparing with controls was observed (percentage TEWETGQI+ CD8+ T cells 2.2 vs. 0.2). The performance of c-di-AMP and ODN-CpG for boosting the immune response to a mucosal DNA-prime showed a balanced TH1/TH2/TH17 profile for c-di-AMP compared with ODN-CpG TH1 profile [(IFN: 1370 vs. 706?. IL-17: 280 vs. 25?. IL-2: 228 vs. 240. IL-4: 32 vs.15)SFU/106 cells for each adjuvant]. C-di-AMP boost resulted in enhanced systemic CD8+ T cell response (%TEWETGQI+ CD8+ T cells 1-0.5-0.07) for c-di-AMP, ODN-CpG and control respectively. Vaccinated animals were able to: 1- control parasite at the site of infection and parasitemia, 2- lower weight loss and tissue damage, and 3- increase survival. Conclusions: Antigen design combine with STING agonists represent a promising tools for vaccines against parasitic diseases.