Source: http://www.asmscience.org/content/book/10.1128/9781555818005.chap37
Timestamp: 2019-04-21 02:41:40+00:00

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The immune response to Helicobacter pylori is remarkably diverse. Evidence from human and animal studies has shown that the immune system expends substantial energy in response to H. pylori. Recent findings show that the survival of H. pylori may also be linked to its capacity to negatively select T cells via induction of apoptosis. It is precisely because H. pylori polarizes the type and magnitude of the host response that immunization may be viewed as a means to deviate a Th1-dominant response resulting in infection and gastritis to another immunologic state capable of interfering with H. pylori persistence and disease. There is now direct evidence that the proinflammatory cytokine macrophage migration inhibitory factor inactivates transcription of the p53 tumor suppressor and that immune deviation can lessen the severity of chronic gastritis and limit the evolution of gastric atrophy. Animal models of helicobacter vaccine immunity have been discussed in this chapter. The initial vaccine studies employed bacterial lysates delivered orally with cholera toxin (CT) as a prototype mucosal adjuvant. However, the complex nature of whole-cell vaccines and their potential for eliciting undesirable immune reactions have favored the use of purified recombinant antigens for vaccine development. The construction of additional mutant labile toxin (LT) molecules, as well as the design of novel CTA-based fusion protein adjuvants and nanoparticulate delivery systems with IL-12-dependent adjuvant activity, should further encourage work into the search for clinically viable mucosal adjuvants for H. pylori vaccines.
Vaccination with H. pylori. Groups of C57BL/6 wild-type donor mice were immunized intranasally with 100 µg H. pylori lysate antigen and 10 µg CT adjuvant, or with CT adjuvant alone. H. pylori immunization protected from infection relative to treatment with CT alone (2.9 × 103 vs. 2.4 × 105 CFU/biopsy, respectively; p < 0.0001 by Wilcoxon rank sum analysis). Spleen Th-cell effectors were isolated from protected donor mice and expanded in vitro with H. pylori lysate, IL-2, and IL-4. H. pylori-specific CD4+ T cells were then magnetically sorted and adoptively transferred (106) by intravenous injection into groups of C57BL/6, MHC class II-/-, or CD4-/- recipient mice. The mice were subsequently challenged with H. pylori, and immune protection was assessed 2 weeks later by quantitative bacterial culture. Micrographs show representative cross sections (7 μm) of stomach from the indicated strains. T cells were stained with anti-TCRβ and anti-CD4, and the mean frequency per mm3 of stomach was derived from serial sections. The circles enclose TCRαβ+CD4+ cells. The H. pylori infection density represents the mean CFU/biopsy × 105. Protection represents the extent of attenuation of the infection in adoptively transferred mice compared with untreated mice, analyzed by Wilcoxon rank sum test. Adapted from reference 87.
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