Article Text

other Versions

PDF
Genetically modified enterotoxigenic escherichia coli vaccines induce mucosal immune responses without inflammation
  1. Alexandra Daley (a.c.daley{at}qmul.ac.uk)
  1. Institute of Cell and Molecular Science, Barts & The London School of Medicine, London, United Kingdom
    1. Roger Randall (roger.randall7{at}btinternet.com)
    1. Acambis plc, Cambridge, United Kingdom
      1. Michael Darsley (darsley{at}acebiosciences.com)
      1. ACE Biosciences A/S, Copenhagen, Denmark
        1. Naheed Choudhry (naheedc76{at}aol.com)
        1. Institute of Cell and Molecular Science, Barts & The London School of Medicine, London, United Kingdom
          1. Nicola Thomas (nicola-paul.thomas{at}virgin.net)
          1. Acambis plc, Cambridge, United Kingdom
            1. Ian R Sanderson (i.r.sanderson{at}qmul.ac.uk)
            1. Institute of Cell and Molecular Science, Barts & The London School of Medicine, London, United Kingdom
              1. Nicholas Croft (n.m.croft{at}qmul.ac.uk)
              1. Institute of Cell and Molecular Science, Barts & The London School of Medicine, London, United Kingdom
                1. Paul Kelly (m.p.kelly{at}qmul.ac.uk)
                1. Institute of Cell and Molecular Science, Barts & The London School of Medicine, London, United Kingdom

                  Abstract

                  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. We hypothesised that three genetically attenuated ETEC strains, one with a genetic addition, would be immunogenic and safe and we evaluated them in the first licensed UK release of genetically modified oral vaccines. Design Phase 1 studies of safety and immunogenicity

                  Setting Teaching Hospital in London Patients Volunteers of both sexes (n=98) Interventions Varying oral doses of any of three oral vaccines, or placebo.

                  Main outcome measures Peripheral blood responses were measured as serum antibodies (IgG or IgA) by ELISA, antibody secreting cell (ASC) responses by 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 (WGLF).

                  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 IL-8 or IL-6 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.

                  • ETEC
                  • genetic modification
                  • mucosal immunology
                  • vaccine
                  • whole gut lavage

                  Statistics from Altmetric.com

                  Request permissions

                  If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

                  Linked Articles

                  • Digest
                    Robin Spiller Emad M El-Omar