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

MARTINEZ F.L.; CORIA M.L.; BRUNO L.; PUEBLAS CASTRO C.V.; CASSATARO J.

Congreso; XII Congress of the Latin American Association of Immunology; 2018

Enterotoxigenic E. coli (ETEC) is the most common cause of bacterial diarrhea indeveloping countries. Both naturally acquired infection and oral-mucosal vaccination againstheat-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 practicaluse in humans, a double mutant of LT (dmLT) which is less toxic and retains its adjuvantproperties 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 formulationsagainst infectious diseases. Previously, it has been shown that this protein can protect coadministeredAgs from digestion and it can also trigger and direct the type of immuneresponses against the Ag. In this work our aim was to investigate the effect of U-Omp19 codeliveryon dmLT immunogenicity and protective efficacy in vivo. To this end inbred BALB/cor outbred CD1 mice were orally immunized, according to different protocols, with i) salineii) 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 ELISAevery week and after last immunization mice were challenged orally with LT enterotoxin(patent mouse gut assay). Results obtained indicated that co-delivery of U-Omp19increased (P