Generation of Helicobacter pylori Ghosts by PhiX Protein E-Mediated Inactivation and Their Evaluation as Vaccine Candidates

Infection and Immunity - Tập 71 Số 1 - Trang 109-116 - 2003
Klaus Panthel1, Wolfgang Jechlinger2, Alexander Matis2, Manfred Rohde3, Michael P. Szostak4, Werner Lubitz4,2, Rainer Haas1
1Max von Pettenkofer Institute for Hygiene and Medical Microbiology, LMU Munich
2Institute of Microbiology and Genetics, University of Vienna.
3Department of Microbial Pathogenicity and Vaccine Research, GBF Braunschweig, Germany
4BIRD-C GmbH, Vienna, Austria

Tóm tắt

ABSTRACT Bacterial ghosts are empty cell envelopes, which may be generated by the controlled expression of the PhiX174 lysis gene E in gram-negative bacteria to obtain vaccine candidates. We describe here the application of this technology to Helicobacter pylori . The lysis gene cassette was cloned into an Escherichia coli-Helicobacter pylori shuttle vector and introduced into an H. pylori recipient strain by bacterial conjugation. Temperature induction of the lysis gene cassette revealed a quantitative killing of the H. pylori culture without induction of lysis-resistant bacteria. Biochemical and transmission electron microscopic studies identified structurally intact H. pylori. Prophylactic oral vaccination experiments using these H. pylori ghosts in the BALB/c mouse model showed a significant reduction of the bacterial load in the ghost group, as measured by a quantitative bacterial reisolation procedure. Ten of 10 and 5 of 10 mice were protected, respectively, without the use of a mucosal adjuvant. Coadministration of ghosts with cholera toxin as mucosal adjuvant resulted in a complete protection of 10 of 10 and 8 of 8 mice against H. pylori challenge, with three animals showing a sterile immunity.

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Infection and Immunity

Tập 71 Số 1

109-116

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