Brucella abortus U-Omp19 improves the immune response and protective capacity of enterotoxigenic Escherichia coli (ETEC) antigens

MARTINEZ, FRANCO LUIS; CORIA, LORENA; BRUNO LAURA; PASQUEVICH KARINA ALEJANDRA; DARRIBA, MARIA LAURA; MARIANELA V. CARABAJAL; VICKERS, T; FLECKESTEIN, J; CASSATARO JULIANA

Congreso; LXV Reunión Anual de la Sociedad Argentina de Inmunología (SAI).; 2017

 Enterotoxigenic E. coli (ETEC) is the most common causeof bacterial diarrhea both among children in developing countries and intravelers to these regions. Both naturally acquired infection and oral-mucosalvaccination against ETEC enterotoxins, colonization factors or adhesins caninduce protective immunity. EtpA, an extracellular ETEC adhesin, is a novelantigen (Ag) with immunogenic and protective capacity found recently.We propose touse a bacterial protease inhibitor, U-Omp19 from Brucella abortus, as platform to deliver antigens in oralformulations against infectious diseases since this protein can protectantigens (Ags) from digestion and it can also trigger and direct the type ofimmune responses. Thus in this work our aim was to investigate the effect ofU-Omp19 co-delivery on EtpA immunogenicity and protective efficacy. To this endinbread BALB/c and outbread CD1 mice were orally immunized with i) saline ii)EtpA iii) EtpA+Omp19 iv) EtpA+dmLT or v) EtpA+dmLT+Omp19. Different doses ofEtpA were studied alone or plus adjuvants. Fecal and serum anti-EtpA andanti-LT antibodies (Abs) were evaluated by ELISA. Cellular immune responses orthe protective capacity of formulations against oral challenge with ETEC H10407were also evaluated.Results obtainedindicated that U-Omp19 co-delivery increased mucosal anti-EtpA or anti-LT Abs(IgA in fecal extracts) and induced EtpA-specific IgA and IgG producing memoryB cells in bone marrows. U-Omp19 improved Ag-specific IFN-γ and IL-17 responsein spleens (P<0.05) and mesenteric lymph nodes (P<0.01). Moreover,U-Omp19, when co-delivered with EtpA or with lower doses of dmLT and EtpAinduced significant protection (P<0.05) against oral challenge with ETEC H10407,while the Ags alone did not.All together ourresults indicate that U-Omp19 can help to reduce Ag dose and could be a goodcandidate to be included in new vaccine formulations against ETEC.