RT Journal Article SR Electronic T1 Genetically modified enterotoxigenic Escherichia coli vaccines induce mucosal immune responses without inflammation JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 1550 OP 1556 DO 10.1136/gut.2006.112805 VO 56 IS 11 A1 Alexandra Daley A1 Roger Randall A1 Michael Darsley A1 Naheed Choudhry A1 Nicola Thomas A1 Ian R Sanderson A1 Nick M Croft A1 Paul Kelly YR 2007 UL http://gut.bmj.com/content/56/11/1550.abstract AB Objective: Enterotoxigenic Escherichia coli (ETEC) is a major cause of acute diarrhoea in children in the developing world, in travellers and in the military. Safe, effective vaccines could reduce morbidity and mortality. As immunity to ETEC is strain specific, the ability to create vaccines in vitro which express multiple antigens would be desirable. It was hypothesised that three genetically attenuated ETEC strains, one with a genetic addition, would be immunogenic and safe, and they were evaluated in the first licensed UK release of genetically modified oral vaccines.Methods: Phase 1 studies of safety and immunogenicity were carried out at a Teaching Hospital in London. Varying oral doses of any of three oral vaccines, or placebo, were administered to volunteers of both sexes (n = 98). Peripheral blood responses were measured as serum antibodies (IgG or IgA) by ELISA, antibody-secreting cell (ASC) responses by enzyme-linked immunospot (ELISPOT), and antibody in lymphocyte supernatant (ALS) by ELISA. Mucosal antibody secretion was measured by ELISA for specific IgG and IgA in whole gut lavage fluids (WGLFs).Results: Significant mucosal IgA responses were obtained to colonisation factors CFA/I, CS1, CS2 and CS3, both when naturally expressed and when genetically inserted. Dose–response relationships were most clearly evident in the mucosal IgA in WGLF. Vaccines were well tolerated and did not elicit interleukin (IL) 8 or IL6 secretion in WGLF.Conclusions: Genetically modified ETEC vaccines are safe and induce significant mucosal IgA responses to important colonisation factors. Mucosal IgA responses were clearly seen in WGLF, which is useful for evaluating oral vaccines.