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Correlation of T cell response and bacterial clearance in human volunteers challenged with H. pylori revealed by randomized controlled vaccination with Ty21a-based Salmonella vaccines
  1. Toni Aebischer (toni.aebischer{at}ed.ac.uk)
  1. Max Planck Institute for Infection Biology, Berlin, Germany
    1. Dirk Bumann (dirk.bumann{at}unibas.ch)
    1. Max Planck Institute for Infection Biology, Berlin, Germany
      1. Hans-Joerg Epple (hans-joerg.epple{at}charite.de)
      1. Charite Campus Benjamin Franklin, Berlin, Germany
        1. Wolfram Metzger (wgmetzger{at}yahoo.com)
        1. Max Planck Institute for Infection Biology, Berlin, Germany
          1. Thomas Schneider (thomas.schneider{at}charite.de)
          1. Charite Campus Benjamin Franklin, Berlin, Germany
            1. Georgy Cherepnev (georg_cherepnev{at}hotmail.com)
            1. Max Planck Institute for Infection Biology, Berlin, Germany
              1. Anna K Walduck (awalduck{at}unimelb.edu.au)
              1. Max Planck Institute for Infection Biology, Berlin, Germany
                1. Desiree Kunkel (desiree.kunkel{at}charite.de)
                1. Charite Campus Benjamin Franklin, Berlin, Germany
                  1. Verena Moos (verena.moos{at}charite.de)
                  1. Charite Campus Benjamin Franklin, Berlin, Germany
                    1. Christoph Loddenkemper (christoph.loddenkemper{at}charite.de)
                    1. Charite Campus Benjamin Franklin, Berlin, Germany
                      1. Irina Jiadze (irina.jiadze{at}charite.de)
                      1. Charite Campus Benjamin Franklin, Berlin, Germany
                        1. Michael Panasyuk (georg_cherepnev{at}hotmail.com)
                        1. Kazan State University, Kazan, Russian Federation
                          1. Manfred Stolte (pathologie.klinikum-bayreuth{at}t-online.de)
                          1. Klinikum Bayreuth, Bayreuth, Germany
                            1. David Y Graham (dgraham{at}bcm.tmc.edu)
                            1. Veterans Affairs Medical Center Houston, Texas, United States
                              1. Martin Zeitz (martin.zeitz{at}charite.de)
                              1. Charite Campus Benjamin Franklin, Berlin, Germany
                                1. Thomas F. Meyer (tfm{at}mpiib-berlin.mpg.de)
                                1. Max Planck Institute for Infection Biology, Berlin, Germany

                                  Abstract

                                  Background: H. pylori remains a global health hazard and vaccination would be ideal for its control. Natural infection appears not to induce protective immunity. Thus, the feasibility of a vaccine for humans is doubtful.

                                  Methods: In two prospective, randomized, double blind, controlled studies (Paul Ehrlich Institute application no. 0802/02, no. 1097/01) live vaccines against H. pylori were tested in human volunteers seronegative for, and without evidence of active H. pylori infection. Volunteers (n=58) were immunized orally with Salmonella enterica serovar Typhi Ty21a expressing H. pylori urease or HP0231, or solely with Ty21a and then challenged with 2x105 cagPAI- H. pylori. Adverse events, infection, humoral, cellular and mucosal immune response were monitored. Gastric biopsies were taken before and after vaccination, and post challenge. Infection was terminated with antibiotics.

                                  Results: Vaccines were well tolerated. Challenge infection induced transient, mild to moderate dyspeptic symptoms, and histological and transcriptional changes in the mucosa known from chronic infection. Vaccines did not show satisfactory protection. However, 13 of 58 volunteers, 8 vaccinees and 5 controls, became breath test negative and either cleared H. pylori (5/13) completely, or reduced H. pylori burden (8/13). H. pylori-specific T helper cells were detected in 9 of these 13 (69%), but only in 6 of 45 (13%) breath test positive volunteers (P=0.0002; Fisher's exact test). T cells were either vaccine induced or pre-existing, depending on volunteer.

                                  Conclusion: Challenge infection offers a controlled model for vaccine testing. Importantly, it revealed evidence for T cell mediated immunity against H. pylori infection in humans.

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