Oral Multicomponent DNA Vaccine Delivered by Attenuated Salmonella Elicited Immunoprotection against American Trypanosomiasis.

SILVIA I CAZORLA; MARINA N MATOS; NATACHA CERNY; CAROLINA RAMIREZ; ANDRES SANCHEZ ALVERTI; AUGUSTO E BIVONA; CELINA MORALES; CARLOS A GUZMAN; EMILIO MALCHIODI

JOURNAL OF INFECTIOUS DISEASES

UNIV CHICAGO PRESS

Año: 2015 p. 698 - 707

0022-1899

We reported that attenuated Salmonella (S) carrying plasmids encoding the cysteine protease cruzipain (Cz) protects against Trypanosoma cruzi infection. Here, we evaluated whether immunoprotection could be improved by the oral co-administration of three Salmonella carrying the plasmids encoding the antigens Cz, Tc52 and Tc24. SCz+STc52+STc24 immunized mice presented an increased antibody response against each antigen compared with single antigen immunized groups, as well as higher trypomastigotes antibodies-mediated lyses and cell invasion inhibition compared with controls. SCz+STc52+STc24 immunized and challenged mice rendered lower parasitemia. Weight loss after infection was detected in all mice except in the SCz+STc52+STc24 group. Moreover, cardiomyopathy-associated enzymes activity was significantly lower in SCz+STc24+STc52 compared to controls. Little or no abnormalities were found in muscle tissues of SCz+STc24+STc52 infected mice, whereas controls presented inflammatory foci, necrosis and amastigote nests. We concluded that a multicomponent approach targeting several invasion and metabolic mechanisms improves protection compared with single component vaccines.