Immunoprotection against T.cruzi infection elicited by a multicomponent vaccine

CAZORLA SI, MATOS MN, RAMIREZ CV, SANCHEZ-ALBERTI A, MALCHIODI EL

Congreso; First French - Argentine Immunology Congress.LVIII Reunión Anual de la Sociedad Argentina de Inmunología; 2010

We have previously demonstrated that Salmonella enterica as DNA delivery system for the major cystein proteinase of T. cruzi, cruzipain (SCz), is able to induce immunoprotection against Chagas disease. To improve the performance of this DNA vaccine, we tested the co-administration of SCz and Salmonella (S) carrying genes encoding Tc52 (a thiol-transferase) and Tc24 (a 24 kDa flagellar calcium binding protein). Mice were immunized with: GI- PBS (Control), GII: SCz, GIII: STc52; GIV: STc24; GV: SCz+STc24+STc52. We found that only antibodies generated in GV vaccinated mice were able to increase the complement-mediated killing of T. cruzi (p<0.005). On contrary, all immunized mice displayed significant DTH immune response against the antigen they were vaccinated, with p<0.001 for GII, p<0.01 (GIII) and p<0.001 (GIV), compared with controls. Mice vaccinated with the multicomponent vaccine (GV) elicited strong DTH against Cz, Tc52 and Tc24 (p<0.001, p<0.05 and p<0.01, respectively). Trypomastigote challenge rendered a significant decrease in parasitemia levels in GII, GIII and GV, compared with control. When we analyzed the area under the curve of parasitemia, GV presented 6 fold reduction in the number of circulating parasites respect to GI (p=0.016). By contrast, mice vaccinated with STc24 were not able to control the infection showing similar parasitemia than control. As indirect parameters of the protection we also analyzed mice weight. While controls presented an important weight lose; GV maintained their weight during the acute phase of the infection (p=0.0095). The activity of serum CPK and LDH, as enzyme markers of muscle injury, was significant lower in GV vaccinated mice comparing with controls (p <0.005 and p <0.001 for CK and LDH, respectively). We conclude that immunization of Salmonella as DNA delivery system for Cz, Tc24 and Tc52 generated an strong immune response able to improved the protection against T. cruzi infection elicited by each antigens.