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Infect Immun, February 1998, p. 581-586, Vol. 66, No. 2
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Mice Are Protected from Helicobacter
pylori Infection by Nasal Immunization with Attenuated
Salmonella typhimurium phoPc Expressing
Urease A and B Subunits
Irène E.
Corthésy-Theulaz,1,*
Sally
Hopkins,2
Daniel
Bachmann,1
Pierre F.
Saldinger,1
Nadine
Porta,1
Rainer
Haas,3
Yan
Zheng-Xin,4
Thomas
Meyer,4
Hanifa
Bouzourène,5
André L.
Blum,1 and
Jean-Pierre
Kraehenbuhl2
Division of Gastroenterology, Department of
Internal Medicine CHUV,1 and
Institute
of Pathology,5 Lausanne University, Lausanne,
and
Biochemistry Institute and ISREC,
Epalinges,2 Switzerland, and
Max von
Pettenkofer Institut, Munich,3 and
Max
Planck Institut für Biologie,
Tübingen,4 Germany
Received 27 August 1997/Returned for modification 22 October
1997/Accepted 28 November 1997
Live Salmonella typhimurium phoPc bacteria
were tested as mucosal vaccine vectors to deliver Helicobacter
pylori antigens. The genes encoding the A and B subunits of
H. pylori urease were introduced into S. typhimurium phoPc and expressed under the
control of a constitutive tac promoter (tac-ureAB) or a
two-phase T7 expression system (cT7-ureAB).
Both recombinant Salmonella strains expressed the two
urease subunits in vitro and were used to nasally immunize BALB/c mice.
The plasmid carrying cT7-ureAB was stably inherited by
bacteria growing or persisting in the spleen, lungs, mesenteric or
cervical lymph nodes, and Peyer's patches of immunized mice,
while the plasmid carrying tac-ureAB was rapidly lost.
Spleen and Peyer's patch CD4+ lymphocytes from mice
immunized with S. typhimurium phoPc
cT7-ureAB proliferated in vitro in response to urease,
whereas cells from mice given S. typhimurium
phoPc alone did not. Splenic CD4+ cells
from mice immunized with phoPc
cT7-ureAB secreted gamma interferon and interleukin 10, while Peyer's patch CD4+ cells did not secrete either
cytokine. Specific H. pylori anti-urease immunoglobulin G1 (IgG1) and IgG2A antibodies were detected
following immunization, confirming that both Th1- and Th2-type
immune responses were generated by the live vaccine.
Sixty percent of the mice (9 of 15) immunized with S. typhimurium phoPc cT7-ureAB were found to
be resistant to infection by H. pylori, while all mice
immunized with phoPc tac-ureAB (15 of 15) or phoPc (15 of 15) were infected.
Our data demonstrate that H. pylori urease delivered
nasally by using a vaccine strain of S. typhimurium can trigger Th1- and Th2-type
responses and induce protective immunity against
Helicobacter infection.
*
Corresponding author. Mailing address: Department of
Internal Medicine, Division of Gastroenterology, CHUV - BH-19N-624,
CH-1011 Lausanne, Switzerland. Phone: 41 21 314 06 85. Fax: 41 21 314 06 84. E-mail: Irene.CorthesyTheulaz{at}ipharm.unil.ch.
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