Chagas disease vaccine based on antigen engineering and sting agonist.

SANCHEZ ALBERTI A, BIVONA AE, CERNY N, CARDOSO LANDABURU AC, SCHULZE K, WEIßMANN S, EBENSEN T, GUZMAN C, CAZORLA SI, MALCHIODI EL

Buenos Aires

Congreso; I Meeting LASID, FAIC, SAI.; 2015

Sociedad Argentina de Inmunologia

Background: ChagasDisease, is a potentially life-threatening illness cause by the protozoan parasite Trypanosomacruzi. WHO recognize it as a neglected tropical disease, which affects 12million people in Latin America. After 100 years of itsdiscovery, no effective vaccine to prevent or treat the infection is approved. Methods: rTraspain, atrivalent immunogen was rationally designed based on the structural signatureand immunogenic ability of each component. Novel adjuvants, as STING Agonistswere employed in combination with recombinant rProtein orDNA-prime+rProtein-boost in vaccination protocols.Results: Antibodies raised against rTraspain blocked in-vitro infection (60% vs. preimmune serum). ELISPOTassay showed a balanced TH1/TH2/TH17 profile for immunized groups. An expansionof pathogen specific CD8+ T lymphocytes comparing with controls wasobserved (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 amucosal DNA-prime was compared. A balanced TH1/TH2/TH17profile for c-di-AMP compared with ODN-CpG TH1 profile [(IFNg: 1370 vs. 706?.IL-17: 280 vs. 25?. IL-2: 228 vs. 240. IL-4: 32 vs.15) SFU/106cells for each adjuvant] was obtained. c-di-AMP boost resulted in enhancedsystemic 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- controlparasite at the site of infection and parasitemia, 2- lower weight loss and tissuedamage, and 3- increase survival. Conclusions: Antigen design combinewith STING agonists represent a promising tools for vaccines against parasiticdisease.