Vaccination of mice with live recombinant Salmonella typhimurium aroA against H. pylori: parameters associated with prophylactic and therapeutic vaccine efficacy

Koesling, Jan; Lucas, Bernadette; Develioglou, Leyla; Aebischer, Toni; Meyer, Thomas F.

doi:10.1016/s0264-410x(01)00355-3

Cited by 31 publications

(20 citation statements)

References 51 publications

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“…The finding that control mice vaccinated with the S. Typhimurium 'carrier' also exhibit reductions in H. pylori numbers is consistent with previous reports from studies in both mice and humans [16,24,32]. While vaccinating with the carrier alone had some protective effect, it was seldom as effective as vaccination with H. pylori-specific antigen, which consistently results in a further 1 log reduction in bacterial numbers.…”

Section: Discussionsupporting

confidence: 90%

“…This reduction was modest (1.8-fold) on day 3, although statistically significant (po0.04), and became substantial by days 7 and 21 (ten-fold, po0.004 and 100-fold, po0.0001, respectively). Analysis at later time points (day 35 and day 70, 1 year) revealed that the degree of protection did not further increase after day 21 (data not shown) [24,25]. It is noteworthy that carrier-vaccinated C57BL/6 mice also exhibited reductions in H. pylori colonisation compared with the control non-vaccinated mice ('carrier effect'), and this reduction was statistically significant at both 7 and 21 days post challenge (po0.003).…”

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confidence: 91%

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Local recall responses in the stomach involving reduced regulation and expanded help mediate vaccine‐induced protection against Helicobacter pylori in mice

Becher¹,

Deutscher²,

Simpfendorfer³

et al. 2010

Eur J Immunol

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Helicobacter pylori is recognised as the chief cause of chronic gastritis, ulcers and gastric cancer in humans. With increased incidence of treatment failure and antibiotic resistance, development of prophylactic or therapeutic vaccination is a desirable alternative. Although the results of vaccination studies in animal models have been promising, studies in human volunteers have revealed problems such as 'post-immunisation gastritis' and comparatively poor responses to vaccine antigens. The focus of this study was to compare the gastric and systemic cellular immune responses induced by recombinant attenuated Salmonella Typhimurium-based vaccination in the C57BL/6 model of H. pylori infection. Analysis of lymphocyte populations in the gastric mucosa, blood, spleen, paragastric LN and MLN revealed that the effects of vaccination were largely confined to the parenchymal stomach rather than lymphoid organs. Vaccine-induced protection was correlated with an augmented local recall response in the gastric mucosa, with increased proportions of CD4 1 T cells, neutrophils and reduced proportions of CD4 1 Treg. CD4 1 T cells isolated from the stomachs of vaccinated mice proliferated ex vivo in response to H. pylori antigen, and secreted Th1 cytokines, particularly IFN-c. This detailed analysis of local gastric immune responses provides insight into the mechanism of vaccine-induced protection.Key words: Helicobacter pylori . Stomach . Treg cells . Vaccine IntroductionHelicobacter pylori is a Gram-negative spiral bacterium that infects the mucous gel layer of the human stomach. Infection is chronic and causes a range of diseases ranging from acute to chronic gastritis, ulcers and, in a small proportion of patients, gastric adenocarcinoma [1].The treatment of H. pylori disease is not straightforward. The most commonly used combination antibiotic therapy, amoxicillin plus clathromycin and a proton pump inhibitor, now only achieve a cure in o80% of cases [2]. This efficacy rate is substantially less than the 495% rate that is deemed acceptable for most other infectious diseases. A prophylactic or therapeutic vaccine would be a cost-effective way to control H. pylori-induced disease.Vaccination is effective in animal models, with 10-to 100-fold reductions (but not sterile immunity) in bacterial colonisation reported in a variety of experimental animals, following immunisation by either oral or parenteral routes (reviewed in [3][4][5]). Oral (mucosal route) vaccination is desirable for a human H. pylori vaccine because of the ease of delivery and, for a live vaccine, the necessity of a single dose is also attractive. 2778with issues such as poor immunogenicity [6], and adverse reactions [7], presenting serious obstacles to further progression of a human vaccine [8]. The reasons for this failure probably result from apparently opposing aspects of the immune response to vaccination. On the one hand vaccination causes 'post-immunisation gastritis' a local inflammatory responses in the stomach in many animal and human recipients, a...

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Section: Discussionsupporting

confidence: 90%

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confidence: 91%

Local recall responses in the stomach involving reduced regulation and expanded help mediate vaccine‐induced protection against Helicobacter pylori in mice

Becher¹,

Deutscher²,

Simpfendorfer³

et al. 2010

Eur J Immunol

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“…La utilización de cepas atenuadas de Salmonella que expresan antígenos a elección es una alternativa a los protocolos de vacunación con lisados totales. Koesling y cols 24 observaron una reducción significativa de la carga bacteriana al inmunizar profilácticamente con una dosis única de Salmonella enterica serovar Typhimurium con un sistema de expresión constitutivo de las subunidades A y B de la ureasa (UreAB) en ratones C57BL/6 y BALB/c. En modalidad terapéutica sólo se observa reducción de la carga en ratones C57BL/ 6 24 .…”

Section: Factibilidad De Una Vacuna: Modelos Animalesunclassified

“…Koesling y cols 24 observaron una reducción significativa de la carga bacteriana al inmunizar profilácticamente con una dosis única de Salmonella enterica serovar Typhimurium con un sistema de expresión constitutivo de las subunidades A y B de la ureasa (UreAB) en ratones C57BL/6 y BALB/c. En modalidad terapéutica sólo se observa reducción de la carga en ratones C57BL/ 6 24 . Por otro lado, Londoño y cols 25 obtuvieron resultados similares en protección y aumento de la respuesta humoral y celular, caracterizada esta última por un aumento inespecífico en la secreción de citoquinas, al utilizar S. enterica serovar Typhi con un sistema de expresión para UreAB inducible, en modalidad profiláctica.…”

Section: Factibilidad De Una Vacuna: Modelos Animalesunclassified

Vacunas en desarrollo: Helicobacter pylori

2006

Rev. chil. infectol.

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Vaccines under development: Helicobacter pyloriHelicobacter pylori causes gastrointestinal disease including peptic ulcer and gastric cancer. An H. pylori vaccine is relevant because of the high prevalence of the infection and its associated complications. Extensive use of traditional antimicrobial therapies to eradicate H. pylori is not feasable, specially in developing countries, in part because of their high cost, associated adverse effects, the risk of reinfection, and the emergence of antimicrobial drug resistance. Numerous animal studies have been performed to determine infection outcomes and to explore the feasibility of a vaccine eradication or prevention of infection. These animal models with the possible exception of monkeys, have not been sufficient to address fundamental issues due to controversial results. A human model of H. pylori infection needs to be developed aimed to select an optimum vaccine candidate. The ultimate scientific goal will be to develop field studies using advanced vaccine candidates, but the current state of knowledge does is insufficient and has provided such candidates. These studies need to be designed in order to provide relevant information on immunity and pathogenesis associated to H. pylori.

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“…Expression of Ag43 chimeras in Salmonella strains. Attenuated Salmonella strains have been shown to be effective live vaccine strains and candidates for recombinant vaccine delivery systems (31,40,48). We have previously shown that Ag43 can be transported to and displayed on the surface of a wide range of gram-negative bacteria (27).…”

Section: Constructionmentioning

confidence: 99%

Antigen 43-Mediated Autotransporter Display, a Versatile Bacterial Cell Surface Presentation System

et al. 2002

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Antigen 43 (Ag43), a self-recognizing outer membrane protein of Escherichia coli, has been converted into an efficient and versatile tool for surface display of foreign protein segments. Ag43 is an autotransporter protein characterized by the feature that all information required for transport to the outer membrane and secretion through the cell envelope is contained within the protein itself. Ag43 consists of two subunits (␣ and ␤), where the ␤-subunit forms an integral outer membrane translocator to which the ␣-subunit is noncovalently attached. The simplicity of the Ag43 system makes it ideally suited as a surface display scaffold. Here we demonstrate that the Ag43 ␣-module can accommodate and display correctly folded inserts and has the ability to display entire functional protein domains, exemplified by the FimH lectin domain. The presence of heterologous cysteine bridges does not interfere with surface display, and Ag43 chimeras are correctly processed into ␣-and ␤-modules, offering optional and easy release of the chimeric ␣-subunits. Furthermore, Ag43 can be displayed in many gram-negative bacteria. This feature is exploited for display of our chimeras in an attenuated Salmonella strain.

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Vaccination of mice with live recombinant Salmonella typhimurium aroA against H. pylori: parameters associated with prophylactic and therapeutic vaccine efficacy

Cited by 31 publications

References 51 publications

Local recall responses in the stomach involving reduced regulation and expanded help mediate vaccine‐induced protection against Helicobacter pylori in mice

Local recall responses in the stomach involving reduced regulation and expanded help mediate vaccine‐induced protection against Helicobacter pylori in mice

Vacunas en desarrollo: Helicobacter pylori

Antigen 43-Mediated Autotransporter Display, a Versatile Bacterial Cell Surface Presentation System

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