Therapeutic immunization against Helicobacter mustelae in naturally infected ferrets

Cuenca, Rafaela; Blanchard, TG; Sj, Czinn; Nedrud, J.G.; Tp, Monath; Lee, CK; Redline, RW

doi:10.1053/gast.1996.v110.pm8964402

Cited by 102 publications

(71 citation statements)

References 3 publications

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“…Thus, the normal immune response has some protective effect. Second, stimulation of the immune response by vaccination in a variety of animal species markedly decreases colonization in response to bacterial challenge (1,2,5,6,11,12,14,17,25). In mice, vaccination also reduces the bacterial load in animals which are already infected (3,21,24).…”

Section: Discussionmentioning

confidence: 99%

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Cure ofHelicobacter pyloriInfection and Resolution of Gastritis by Adoptive Transfer of Splenocytes in Mice

Eaton

Mefford

2001

Infect Immun

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Vaccination suppresses Helicobacter pylori colonization but does not cure infection. Furthermore, postvaccination gastritis, likely induced by enhanced host response to residual colonization, may exacerbate disease. The goal of this study was to determine if adoptive transfer of C57BL/6 splenocytes to C57BL/6scid/scid (severe combined immunodeficient [SCID]) mice cures infection without exacerbating gastritis. H. pylori-infected and uninfected C57BL/6 mice and SCID recipients of normal splenocytes were killed at intervals between 5 and 51 weeks after infection. Colonization and gastritis were quantified, humoral immune responses were determined by enzyme-linked immunosorbent assay, and cellular immune responses were determined by delayed-type hypersensitivity response and by a proliferative response of cultured splenocytes to H. pylori sonicate. In infected C57BL/6 mice, gastritis developed gradually and bacterial colonization diminished but persisted throughout the experiment. In contrast, gastritis in infected recipient SCID mice developed rapidly and bacterial colonization decreased precipitously. Gastritis in those mice peaked 9 weeks after adoptive transfer, however, and began to resolve. By 45 weeks after transfer, gastritis had returned to background levels and bacteria were no longer detectable. Resolution of gastritis and elimination of infection were associated with a cellular but not humoral immune response to H. pylori antigens. These results demonstrate that although the host response fails to clear bacterial colonization in normal mice, enhanced cellular immune responses in recipient SCID mice are capable of clearing H. pylori infection and allowing resolution of gastritis. Thus, immune mechanisms of cure exist, and effective and safe vaccination protocols may be feasible.The startling discovery made in 1983 that a bacterial organism, Helicobacter pylori, is the underlying cause of peptic ulcer disease (27, 39) led to several major changes in the therapy of gastric disease in recent years. First, the realization that peptic ulcer disease (and possibly some forms of gastric cancer [32,33]) may be treatable or preventable with antibiotics resulted in rapid development of many excellent treatment protocols. Peptic ulcer disease is now considered an infectious disease and can be cured by elimination of the causative organism, markedly improving the prognosis for those whose infections are curable. It has become apparent, however, that H. pylori infection is not an easy foe. Once infected, people appear to remain infected for life, and even with medical intervention, the organism may persist or recur. In fact, it appears to be true of the gastric helicobacters in general that colonization persists in spite of a strong host immune response, and even bacteria that are susceptible to antibiotics in vitro may be resistant to them in vivo. Thus, we are faced with the task of eliminating a highly resistant pathogen that the normal host itself cannot eliminate.Because of the difficulty of eliminating H. pylori...

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Section: Discussionmentioning

confidence: 99%

“…Many of these have been shown to be at least partly effective in suppressing or eliminating colonization in animal models (2,5,6,11,12,14,17,21,22,24,25,31), and human trials have shown some promise (28). Like treatment regimens, however, vaccine trials have been incompletely effective.…”

mentioning

confidence: 99%

Cure ofHelicobacter pyloriInfection and Resolution of Gastritis by Adoptive Transfer of Splenocytes in Mice

Eaton

Mefford

2001

Infect Immun

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“…21,22 A capacidade de a vacina oral curar a infecção crônica pelo H. pylori provavelmente se deve à diferença qualitativa entre a resposta imune induzida pela vacina e aquela desencadeada pela infecção natural. 25 Apesar do grande empenho dos pesquisadores, estima-se que somente dentro de aproximadamente 10 a 15 anos a vacinação segura e eficaz contra o H. pylori estará disponível.…”

Section: Prevençãounclassified

Aspectos epidemiológicos do Helicobacter pylori na infância e adolescência

2002

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Descritores ResumoRealizou-se revisão da epidemiologia da infecção pelo Helicobacter pylori, com o objetivo de analisar sua importância na infância e adolescência no que se refere à incidência, à prevalência, às vias de transmissão e aos fatores de risco. Para tanto, realizou-se uma pesquisa nas bases de dados Lilacs (OPS/Bireme) e Medline (National Library of Medicine) e no banco de teses da Universidade de São Paulo dos anos de 1983 a 1999. A análise da literatura levou à conclusão de que a infecção pelo Helicobacter pylori é adquirida principalmente durante a infância, apresenta aumento da prevalência com a idade, os principais fatores de riscos estão relacionados ao baixo nível socioeconômico e o mecanismo de transmissão permanece desconhecido. AbstractThe scope of the review is to study the epidemiological aspects of Helicobacter pylori infection and its importance during childhood and adolescence, focusing on incidence, prevalence, transmission and risk factors. The study's references included the following databases: LILACS (PAHO/ Bireme), MEDLINE, the US's National Library of Medicine and the thesis developed at University of São Paulo for the period 1983 to 1999. It was noted that Helicobacter pylori infection is mainly acquired during childhood, age-related prevalence, main risk factors are associated to low socioeconomic status, and its transmission mechanism remains unclear.

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“…131 Therapeutic vaccination has also been successful in ferrets and Rhesus monkeys infected with Helicobacter mustelae and H. pylori, respectively. 132,133 Most of these antigens have been given orally in combination with mucosal adjuvants, which improve their low immunoreactivity. 127 However, the inherent toxicity of mucosal adjuvants has been the major limitation for their use as vaccines in humans.…”

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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Therapeutic immunization against Helicobacter mustelae in naturally infected ferrets

Cited by 102 publications

References 3 publications

Cure ofHelicobacter pyloriInfection and Resolution of Gastritis by Adoptive Transfer of Splenocytes in Mice

Cure ofHelicobacter pyloriInfection and Resolution of Gastritis by Adoptive Transfer of Splenocytes in Mice

Aspectos epidemiológicos do Helicobacter pylori na infância e adolescência

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

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