Immune protection against Trypanosoma cruzi infection: Efficacy of two new generation adjuvants to formulate a subunit vaccine with trans-sialidase antigen

BONTEMPI IVÁN1, CABRERA GABRIEL1, VICCO MIGUEL1, BERTONA DAIANA1, VILLAR SILVINA 2, GONZÁLEZ FLORENCIA2, PUJATO NAZARENA1, NICASTRO ALCIDES3, PÉREZ ANA2, MARCIPAR IVÁN1.

Mar del Plata

Congreso; LXII REUNIÓN ANUAL Sociedad Argentina de Inmunología; 2014

New generations adjuvants are able to enhance the efficacy of recombinant protein vaccines which are considered to be the safer ones but which typically promotes weak Immune responses. ISCOMATRIX (IMX) is a particularly special adjuvant as it has shown to be effective and safe in human clinical trials of vaccines designed to control intracellular infections by promoting a CTL response. Therefore, as a first step we assessed the immune protection achieved using this adjuvant to formulate mutant inactive trans-sialidase (mTS), previously proven to be highly protective against T. cruzi infection. Mice were immunized with mTS-IMX, mTS-IFA (IFA, incomplete Freund adjuvant), mTS (without adjuvant), IMX (without antigen) and PBS. mTS-IMX showed a TS-specific IgG response with titers >106 and high avidity, an increased IgG2a/IgG1 ratio, significant delayed-type hypersensitivity (DTH) reactivity and a balanced IFN-g and IL-10 production, compared to mice immunized with mTS or IMX in PBS or vehicle (PBS) (p<0,01, mTS vs PBS and others groups; Mann Withney test). When these mice where challenged with 1000 T. cruzi, all mTS-IMX immunized mice survived, while mice immunized with mTS alone, IMX or PBS displayed high mortality (p<0,05; mTS vs PBS; Mantel Cox test). Remarkably, compared to the non-immunized mice, mTS-IMX immunized mice had ~50 times less parasitemia during acute infection and presented ~4.5 times lower parasite load in heart-tissue (p<0,01, mTS-IMX vs PBS; Mann Withney test), associated with decreased inflammatory infiltrate and lesions, both in the acute atnd the chronic phase. As a second step, a new assessments was proven with mTS and an adjuvant made in our lab based on IMX composition (ISPA). This new formulation gave comparable high values of antibodies titers, DTH, survivor and low levels of parasitemia with mTS-IMX (p>0,01, mTS-IMX vs mTS-ISPA; Mann Withney test). These results indicates that subunit vaccines may achieve immune protection against T. cruzi.