Development of a Mouse Model of
            <i>Helicobacter pylori</i>
            Infection that Mimics Human Disease

Marchetti, Marta; Aricò, Beatrice; Burroni, Daniela; Figura, Natale; Rappuoli, Rino; Ghiara, P

doi:10.1126/science.7886456

Cited by 554 publications

(394 citation statements)

References 21 publications

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“…VacA is a candidate antigen because immunization with VacA confers protective immunity in a mouse model of H. pylori infection (52,53). We show here that two VacA surfaces are strictly conserved among all surveyed m1 and m2 sequences and propose that these surfaces are under selective pressure to be preserved to mediate receptor-binding and oligomerization functions.…”

Section: Sequence Variation Among Vaca Proteinsmentioning

confidence: 84%

Crystal structure of the Helicobacter pylori vacuolating toxin p55 domain

Gangwer

Mushrush

Stauff

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

140

181

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Section: Sequence Variation Among Vaca Proteinsmentioning

confidence: 84%

Crystal structure of the Helicobacter pylori vacuolating toxin p55 domain

Gangwer

Mushrush

Stauff

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

140

181

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“…102 I strains promote gastric damage similar to that observed in humans. 71,104 To date, studies have shown that CagA is one of the proteins produced by the pathogenicity island (cag PAI). Recent studies using isogenic mutants strains lacking the cagA gene have shown that IL-8 induction may not be directly due to CagA protein but to the products of cag PAI genes.…”

Section: Relevance Of Strain Types Of H Pylori In the Outcome Of Infmentioning

confidence: 99%

“…104,127 These models have permitted the testing of prophylactic and therapeutic vaccines containing different antigens, including whole inactivated cells, 1 bacterial lysates, 128 and several purified antigens. To date, researchers have identified several H. pylori antigens which confer protection against H. pylori infection or in eradicating an already established infection in the murine models, including purified VacA, 104 urease (and its subunits), 129 CagA, 130 heat shock proteins (HspA and HspB), 1 and catalase. 131 Therapeutic vaccination has also been successful in ferrets and Rhesus monkeys infected with Helicobacter mustelae and H. pylori, respectively.…”

Section: Vaccination Development For Clinical Use and Future Of The Hmentioning

confidence: 99%

Helicobacter pylori: recent advances in the study of its pathogenicity and prevention

Aguilar¹,

Ayala²,

Fierros-Zarate³

2001

Salud pública Méx

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Helicobacter pylori has acquired great importance during the last two decades, after being recognized as an important pathogen that infects a great portion of the human population. This microorganism is recognized as the main causal agent of chronic gastritis and duodenal ulcers, and it is associated with the subsequent development of gastric carcinoma. The pathogenic mechanisms of H. pylori and their relation to gastric ailments have not been clearly defined. However, at present it is well established that urease, vacuolating cytotoxin VacA, and the pathogenicity island (cag PAI) gene products, are the main factors of virulence of this organism. Thus, individuals infected with strains that express these virulence factors probably develop a severe local inflammation that may induce the development of peptic ulcer and gastric cancer. The way the infection spreads throughout the world suggests the possibility that there are multiple pathways of transmission. Due to the importance that H. pylori has acquired as a human pathogen, laboratories worldwide are attempting to develop a vaccine that confers long-term immunological protection against infection by this microorganism. Hence, the objective of this review is to present the most relevant findings of the biology of H. Pylori and its interaction with the human host. The full version of this paper is available too at: http:// www.insp.mx/salud/index.html ResumenHelicobacter pylori ha adquirido gran importancia durante las últimas dos décadas, al ser reconocido como un importante patógeno que infecta una gran porción de la población humana. Este microrganismo es reconocido como el principal agente que causa la gastritis crónica y la úlcera duodenal, además de que se ha asociado con el subsecuente desarrollo del carcinoma gástrico. Los mecanismos patogé-nicos de H. pylori y su relación con los padecimientos gás-tricos no se han definido en forma clara. Sin embargo, actualmente está bien establecido que la ureasa, la citotoxina vacuolizante VacA y los productos de los genes de la isla de patogenicidad (cag PAI) son los principales factores de virulencia de este organismo. Así, los individuos infectados con cepas que expresan dichos factores de virulencia, probablemente manifiesten una marcada inflamación local que podría inducir el desarrollo de úlcera péptica y cáncer gástri-co. La manera como la infección se propaga a nivel mundial sugiere la posibilidad de múltiples vías de transmisión. A consecuencia de la importancia que H. pylori ha adquirido como patógeno humano, los laboratorios del mundo se esfuerzan para desarrollar una vacuna que confiera protección inmunológica de larga duración contra la infección por este microorganismo. El objetivo de esta revisión es presentar los hallazgos más relevantes sobre la biología de H. pylori y su interacción con su huésped humano. El texto completo de este artículo también está disponible en:

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“…SPM326, a type I (CagA ϩ VacA ϩ ) H. pylori strain obtained from a human isolate and adapted to the mouse as previously described (21), was used to infect the dogs. Bacteria were grown and harvested as previously described (8) with minor modifications.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Vaccination againstHelicobacter pyloriin the Beagle Dog Experimental Model: Safety, Immunogenicity, and Efficacy

et al. 2004

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Helicobacter pylori is a gram-negative bacterium that colonizes the human gastric mucosa causing gastritis and peptic ulcer and increasing the risk of gastric cancer. The efficacy of current antibiotic-based therapies can be limited by problems of patient compliance and increasing antibiotic resistance; the vaccine approach can overcome these limits. The present study describes the therapeutic vaccination of experimentally H. pyloriinfected beagle dogs, an animal model that reproduces several aspects of the human infection with H. pylori. The vaccine consisted of three recombinant H. pylori antigens, CagA, VacA, and NAP, formulated at different doses (10, 25, or 50 g each) with alum and administered intramuscularly either weekly or monthly. No adverse effects were observed after vaccination and a good immunoglobulin G response was generated against each of the three antigens. Bacterial colonization and gastritis were decreased after the completion of the vaccination cycle, especially in the case of the monthly immunization schedule. In conclusion, therapeutic vaccination in the beagle dog model was safe and immunogenic and was able to limit H. pylori colonization and the related gastric pathology.Helicobacter pylori is a spiral-shaped, gram-negative bacterium that infects the stomach of Ͼ50% of the population worldwide, with higher prevalence in the developing countries. H. pylori induces chronic inflammation of the stomach mucosa, causing chronic gastritis and peptic ulcer (9, 33); moreover, H. pylori infection is related to gastric mucosa-associated lymphoid tissue lymphoma (4) and to an increased risk of gastric cancer (36), as also proved in animal models (13,38).Current therapies, based on one antisecretory agent plus antibiotics, although effective in 80 to 90% of cases, face problems of patient compliance, increasing antibiotic resistance, and possible recurrence or reinfection; in spite of continuous effort to improve these treatments, no major breakthroughs have been achieved in the most recent years (30).To overcome the limits of antibiotic-based therapies, the vaccine approach has been undertaken since the last decade, leading us to identify some relevant bacterial antigens as candidates for vaccines (2). On the other hand, animal models of H. pylori infection have been developed to study the interaction between the bacterium and the host, the mechanisms of immune response to either infection or vaccination, and to determine the efficacy of both prophylactic and therapeutic vaccination (2,17,26,34). Among these animal models, that of the beagle dog reproduces several aspects of the human infection with H. pylori. In fact, in the beagle dog model, intragastric administration of H. pylori results in a long-term chronic infection, characterized by gastritis, epithelial alterations, superficial erosions, and the appearance of macroscopic follicles in the gastric mucosa, mainly in the antral region of the stomach (28,29).Most of the examples of vaccination against H. pylori in animal models reported in the...

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Development of a Mouse Model of Helicobacter pylori Infection that Mimics Human Disease

Cited by 554 publications

References 21 publications

Crystal structure of the Helicobacter pylori vacuolating toxin p55 domain

Crystal structure of the Helicobacter pylori vacuolating toxin p55 domain

Helicobacter pylori: recent advances in the study of its pathogenicity and prevention

Therapeutic Vaccination againstHelicobacter pyloriin the Beagle Dog Experimental Model: Safety, Immunogenicity, and Efficacy

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