Therapeutic Immunisation against hellcobacter Infection

Doidge, Christopher; Gust, Ian D.; Lee, Adrian V.; Buck, F; Hazell, Stuart L.; Manne, Upender

doi:10.1016/s0140-6736(94)90032-9

Cited by 138 publications

(71 citation statements)

References 3 publications

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“…Host responses are thought to contribute to the development of inflammation leading to gastritis or ulceration either by cross-reactive autoimmunity or bystander activation. Correspondingly, Th2-like patterns of immune response are protective against gastritis, and when induced by oral immunisation not only prevent but clear infection in mice [63]. Concurrent helminth infection also protects against the harmful consequences of H felis infection in mice [64].…”

Section: Other Co-evolutionary Candidatesmentioning

confidence: 99%

A missing link in the hygiene hypothesis?

2002

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The incidence of childhood Type I (insulin-dependent) diabetes mellitus has risen in parallel with that of childhood asthma, and the hygiene hypothesis proposes that this is due to reduced stimulation of the immune system by early intercurrent infection. If so, this protective effect is probably mediated by regulatory T lymphocytes. Co-evolutionary partners might have contributed to the development of this form of response, and parasites and the indigenous biota of the gut are plausible candidates. Helminths inhibit the development of atopic disease via induction of regulatory T cells and secretion of Il-10, and pinworms inhibit diabetes development in the non-obese diabetic (NOD) mouse. The most successful human helminth of the western world is the pinworm Enterobius vermicularis, and some 50% of young children in Europe and North America may have been infested around the middle of the twentieth century. Pinworms are benign, usually asymptomatic, and may have immunomodulatory properties that protect against the development of immune-mediated disorders including diabetes and asthma. Their decline in response to improved living conditions might explain a number of features of the epidemiology of childhood atopy and diabetes. The proposed role would be one of immunomodulation rather than disease induction, possibly mediated by interaction with other influences upon the development of the mucosal immune system. This hypothesis could be tested in case-control studies by the development of serological markers or skin testing. The rise of childhood asthma and diabetes There are curious parallels between the epidemiology of the atopic disorders and that of Type I (insulindependent) diabetes mellitus [1]. The prevalence of childhood-onset asthma, hay fever and eczema rose steadily in the second half of the twentieth century, and the highest rates are seen in those with a relatively affluent style of life, living in temperate climates [2,3,4]. Childhood onset Type I diabetes also showed a steady increase over the second half of the last century in most parts of the western world. Atopic disorders and childhood diabetes seem to be relatively infrequent in those with a traditional lifestyle but can be acquired by immigrants to more affluent or westernised areas [5,6]. There is strong evidence that atopic disorders are less likely to arise within large sibships or in children receiving day care [7] and day care could also be protective against the development of Type I diabetes, although evidence for this is not strong [8]. Children from East Germany were three times less likely to report asthma or to show positive skin tests than children in West Germany [9] and the

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Section: Other Co-evolutionary Candidatesmentioning

confidence: 99%

A missing link in the hygiene hypothesis?

2002

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“…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.…”

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

confidence: 99%

“…137 Additionally, the use of non-toxic LTK63 or CT S61F for oral vaccination induces a relatively greater Th2 cell response that can cure and prevent infection in H. felis/ mice models. 128,129,135,139 Thus, with the discovery of the appropriate formulation and routes of administration, it is possible that vaccination could trigger an immune response that differs substantially from that induced by natural infection with H. pylori. Undoubtedly, the continuous efforts of laboratories around the world to develop a vaccine and therapeutic approaches may soon bring an end to the long evolutionary relationship between humankind and Helicobacter pylori.…”

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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“…Prophylactic or therapeutic vaccination against H. pylori is a desirable alternative to control the H. pylori infection (3), and animal studies have proven the feasibility of this approach (9,10,14,16,27,61).…”

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confidence: 99%

Colonization of C57BL/6J and BALB/c Wild-Type and Knockout Mice withHelicobacter pylori: Effect of Vaccination and Implications for Innate and Acquired Immunity

2003

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The gram-negative bacterial pathogen Helicobacter pylori is a major cause of peptic ulcer disease and a risk factor for gastric cancer in humans. Adapted H. pylori strains, such as strain SS1, are able to infect mice and are a useful model for gastric colonization and vaccination studies. In this study we used a streptomycinresistant derivative of H. pylori SS1 to analyze the colonization behavior and the success of vaccination in wild-type (wt) and various knockout mice of the BALB/c and C57BL/6J genetic backgrounds. We here report that BALB/c interleukin-4 knockout (IL-4 ؊/؊ ) mice are weakly overcolonized compared to the wt strain but that the IL-12 ؊/؊ knockout results in a strong overcolonization (500%). Unexpectedly, in the C57BL/6J background the same knockouts behaved in diametrically opposed manners. The IL-4 ؊/؊ mutation caused a 50% reduction and the IL-12 ؊/؊ knockout caused a 95% reduction compared to the wt colonization rate. For C57BL/6J mice we further analyzed the IL-18 ؊/؊ and Toll-like receptor 2 knockout mutations, which showed reductions to 66 and 57%, respectively, whereas mice with the IL-10 ؊/؊ phenotype were hardly infected at all (5%). In contrast, the tumor necrosis factor receptor knockout (p55 ؊/؊ and p55/75 ؊/؊ ) mice showed an overcolonization compared to the C57BL/6J wt strain. With exception of the low-level infected C57BL/6J IL-10 ؊/؊ and IL-12 ؊/؊ knockout mice, all knockout mutants were accessible to a prophylactic vaccination and their vaccination behavior was comparable to that of the wt strains.

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Therapeutic Immunisation against hellcobacter Infection

Cited by 138 publications

References 3 publications

A missing link in the hygiene hypothesis?

A missing link in the hygiene hypothesis?

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

Colonization of C57BL/6J and BALB/c Wild-Type and Knockout Mice withHelicobacter pylori: Effect of Vaccination and Implications for Innate and Acquired Immunity

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