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

SILVIA I. CAZORLA; MARINA N. MATOS; NATACHA CERNY; CAROLINA RAMIREZ; SANCHEZ ALBERTI ANDRES; AUGUSTO E. BIVONA; CELINA MORALES; CARLOS A. GUZMÁN; EMILIO L. MALCHIODI

JOURNAL OF INFECTIOUS DISEASES

UNIV CHICAGO PRESS

Lugar: Chicago; Año: 2014

0022-1899

We have reported that attenuated Salmonella (S) carrying plasmids encoding the cysteine protease cruzipain(Cz) protects against Trypanosoma cruzi infection. Here, we determined whether immunoprotection couldbe improved by the oral coadministration of 3 Salmonella carrying the plasmids that encode the antigens Cz,Tc52, and Tc24. SCz+STc52+STc24?immunized mice presented an increased antibody response against eachantigen compared with those in the single antigen?immunized groups, as well as higher trypomastigotes antibody-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 those inthe SCz+STc52+STc24 group. Moreover, cardiomyopathy-associated enzyme activity was significantly lower inSCz+STc24+STc52?immunized mice compared with controls. Few or no abnormalities were found in muscletissues of SCz+STc24+STc52?immunized mice, whereas controls presented with inflammatory foci, necrosis,and amastigote nests.We conclude that a multicomponent approach that targets several invasion and metabolicmechanisms improves protection compared with single-component vaccines.