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Infection and Immunity, January 2003, p. 109-116, Vol. 71, No. 1
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.1.109-116.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Max von Pettenkofer Institute for Hygiene and Medical Microbiology, LMU Munich,1 Department of Microbial Pathogenicity and Vaccine Research, GBF Braunschweig, Germany,3 Institute of Microbiology and Genetics, University of Vienna,2 BIRD-C GmbH, Vienna, Austria4
Received 22 July 2002/ Returned for modification 24 September 2002/ Accepted 15 October 2002
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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