Oral immunization of mice with lactic acid bacteria producing Helicobacter pylori Urease B subunit partially protects against challenge with Helicobacter felis

被引:83
作者
Corthésy, B
Boris, S
Isler, P
Grangette, C
Mercenier, A
机构
[1] Inst Pasteur, Lab Bacteriol Ecosyst, Lille, France
[2] Univ Vaudois, Ctr Hosp, R&D Lab, Div Immunol & Allergy, Lausanne, Switzerland
[3] Univ Vaudois, Ctr Hosp, Div Gastroenterol, Lausanne, Switzerland
[4] Inst Pasteur, Lab Bacteriol Ecosyst, Lille, France
关键词
D O I
10.1086/444425
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. The development of an efficacious vaccine against infection with Helicobacter pylori, the causative agent of chronic gastritis, peptic ulcer disease, and gastric adenocarcinoma, remains a challenge. Since the use of mucosal adjuvants is limited in human application, we have evaluated the potential of recombinant Lactobacillus strains producing H. pylori urease B (UreB) subunit to deliver this antigen to the gastrointestinal tract. Methods. Mice were injected orally 3 times with a triple dose of recombinant Lactobacillus plantarum NCIMB8826, the recombinant isogenic cell-wall mutant (alr(-) MD007 strain) expressing UreB, or a mixture of recombinant UreB and cholera toxin ( rUreB/CT) as a control. Urease-specific seric immunoglobulin (Ig) G and IgA were measured by use of an enzyme-linked immunosorbent assay. After challenge with Helicobacter felis, stomach infection was examined by use of the rapid urease test and by polymerase chain reaction detection of Helicobacter genomic DNA. Results. Intragastric immunization with both recombinant Lactobacillus strains and rUreB/CT elicited UreB-specific antibodies. After challenge, reduction of H. felis load in the stomachs of mice was observed only after immunization with the recombinant mutant strain MD007 or with rUreB/CT. Conclusions. This is the first report of successful induction of partial protection against H. felis with a mucosal prime-boost regimen in which recombinant Lactobacillus strains were used as antigen-delivery vehicles.
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页码:1441 / 1449
页数:9
相关论文
共 51 条
[41]   Use of mouse models to evaluate the persistence, safety, and immune modulation capacities of lactic acid bacteria [J].
Pavan, S ;
Desreumaux, PD ;
Mercenier, A .
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, 2003, 10 (04) :696-701
[42]   Helicobacter pylori virulence factors and the host immune response:: implications for therapeutic vaccination [J].
Prinz, C ;
Hafsi, N ;
Voland, P .
TRENDS IN MICROBIOLOGY, 2003, 11 (03) :134-138
[43]   Comparison of the immune responses induced by local immunizations with recombinant Lactobacillus plantarum producing tetanus toxin fragment C in different cellular locations [J].
Reveneau, N ;
Geoffroy, MC ;
Locht, C ;
Chagnaud, P ;
Mercenier, A .
VACCINE, 2002, 20 (13-14) :1769-1777
[44]   Immunomodulators and delivery systems for vaccination by mucosal routes [J].
Ryan, EJ ;
Daly, LM ;
Mills, KHG .
TRENDS IN BIOTECHNOLOGY, 2001, 19 (08) :293-304
[45]  
Sambrook J., 1989, MOL CLONING
[46]   Lactobacilli as live vaccine delivery vectors: progress and prospects [J].
Seegers, JFML .
TRENDS IN BIOTECHNOLOGY, 2002, 20 (12) :508-515
[47]   Chemokine mRNA expression in gastric mucosa is associated with Helicobacter pylori cagA positivity and severity of gastritis [J].
Shimoyama, T ;
Everett, SM ;
Dixon, MF ;
Axon, ATR ;
Crabtree, JE .
JOURNAL OF CLINICAL PATHOLOGY, 1998, 51 (10) :765-770
[48]   Biological containment of genetically modified Lactococcus lactis for intestinal delivery of human interleukin 10 [J].
Steidler, L ;
Neirynck, S ;
Huyghebaert, N ;
Snoeck, V ;
Vermeire, A ;
Goddeeris, B ;
Cox, E ;
Remon, JP ;
Remaut, E .
NATURE BIOTECHNOLOGY, 2003, 21 (07) :785-789
[49]   Coinfection modulates inflammatory responses and clinical outcome of Helicobacter felis and Toxoplasma gondii infections [J].
Stoicov, C ;
Whary, M ;
Rogers, AB ;
Lee, FS ;
Klucevsek, K ;
Li, HC ;
Cai, X ;
Saffari, R ;
Ge, ZM ;
Khan, IA ;
Combe, C ;
Luster, A ;
Fox, JG ;
Houghton, JM .
JOURNAL OF IMMUNOLOGY, 2004, 173 (05) :3329-3336
[50]  
Vesa T, 2000, ALIMENT PHARM THER, V14, P823