U-Omp19 from Brucella abortus increases dmLT immunogenicity and improves protection against Heat-Labile Toxin (LT) oral challenge in vivo

MARTINEZ, FRANCO LUIS; PUEBLAS CASTRO, CELESTE; BRUNO, LAURA A.; CORIA, LORENA M.; CASSATARO, JULIANA

Cancun

Congreso; XII Congreso de la Asociación Latinoamericana de Inmunología; 2018

Asociación Latinoamericana de Inmunología

Enterotoxigenic E. coli (ETEC) is the most common cause of bacterial diarrhea in developing countries. Both naturally acquired infection and oral-mucosal vaccination against heat-labile toxin (LT), colonization factors or adhesins can induce protective immunity. So, LT is being used as oral adjuvant/antigen (Ag) in mice. Since its toxicity limits its practical use in humans, a double mutant of LT (dmLT) which is less toxic and retains its adjuvant properties is under clinical trial. U-Omp19 is a protease inhibitor from Brucella spp. with immunoestimulatory properties. We propose to use U-Omp19 as platform to deliver antigens (Ags) in oral formulations against infectious diseases. Previously, it has been shown that this protein can protect co-administered Ags from digestion and it can also trigger and direct the type of immune responses against the Ag. In this work our aim was to investigate the effect of U-Omp19 co-delivery on dmLT immunogenicity and protective efficacy in vivo. To this end inbred BALB/c or outbred CD1 mice were orally immunized, according to different protocols, with i) saline ii) dmLT or iii) dmLT+U-Omp19. Three doses of dmLT were studied alone or plus U-Omp19: 25µg, 12,5µg and 2,5µg. Fecal and serum α-LT antibodies (Abs) were evaluated by ELISA every week and after last immunization mice were challenged orally with LT enterotoxin (patent mouse gut assay). Results obtained indicated that co-delivery of U-Omp19 increased (P