THE DESIGN OF VACCINES AGAINST HELICOBACTER PYLORI AND THEIR DEVELOPMENT
Helicobacter pylori is a gram negative, spiral, microaerophylic bacterium that infects the stomach of more than 50% of the human population worldwide. It is mostly acquired during childhood and, if not treated, persists chronically, causing chronic gastritis, peptic ulcer disease, and in some indivi...
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Veröffentlicht in: | Annual review of immunology 2001-01, Vol.19 (1), p.523-563 |
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Zusammenfassung: | Helicobacter pylori
is a gram negative, spiral, microaerophylic
bacterium that infects the stomach of more than 50% of the human
population worldwide. It is mostly acquired during childhood and, if not
treated, persists chronically, causing chronic gastritis, peptic ulcer disease,
and in some individuals, gastric adenocarcinoma and gastric B cell lymphoma.
The current therapy, based on the use of a proton-pump inhibitor and
antibiotics, is efficacious but faces problems such as patient compliance,
antibiotic resistance, and possible recurrence of infection. The development of
an efficacious vaccine against
H. pylori
would thus offer several
advantages. Various approaches have been followed in the development of
vaccines against
H. pylori
, most of which have been based on the use of
selected antigens known to be involved in the pathogenesis of the infection,
such as urease, the vacuolating cytotoxin (VacA), the cytotoxin-associated
antigen (CagA), the neutrophil-activating protein (NAP), and others, and
intended to confer protection prophylactically and/or therapeutically in animal
models of infection. However, very little is known of the natural history of
H. pylori
infection and of the kinetics of the induced immune responses.
Several lines of evidence suggest that
H. pylori
infection is
accompanied by a pronounced Th1-type CD4
+
T cell response. It
appears, however, that after immunization, the antigen-specific response is
predominantly polarized toward a Th2-type response, with production of
cytokines that can inhibit the activation of Th1 cells and of macrophages, and
the production of proinflammatory cytokines. The exact effector mechanisms of
protection induced after immunization are still poorly understood. The next
couple of years will be crucial for the development of vaccines against
H.
pylori
. Several trials are foreseen in humans, and expectations are that
most of the questions being asked now on the host-microbe interactions will be
answered. |
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ISSN: | 0732-0582 1545-3278 |
DOI: | 10.1146/annurev.immunol.19.1.523 |