This U19 TRIAD Research Project proposal aims to characterize the human T cell response to H. pylori infection in order to develop a vaccine. The strategy employed involves informatic analysis of the H. pylori genome to discover potential T-cell epitopes that will be validated by experimental methodologies in vivo in humanized transgenic mice and ex vivo with gastric tissue and peripheral blood mononuclear cells from H. pylori-infected human subjects. We will discover epitopes that elicit inflammatory responses and investigate how others, which bear similarity to human genome and human microbiome sequences/may assist H. pylori to evade a protective immune response. This project will interface with the TRIAD Toolkit Core for in silico epitope mapping and HLA binding validation of computational predictions. It will also make extensive use of the TRIAD CMI Core services including the HLA transgenic mouse colony, analysis of antigen-specific T cell frequency by ELISpot, and cytokine profiling and multi-functional T cell analysis using flow cytometry. We expect to identify vaccine candidates that lead to protective human responses and plan to interface with the TRIAD Technology Development Project to produce and test a pilot dendritic cell-targeted vaccine with epitopes identified here.
The work proposed addresses the need for a vaccine against H. pylori to prevent inflammation and cancer. Human immune responses to H. pylori proteins will be measured to understand how H. pylori interfaces with the human immune system and the microbes that inhabit the human body.
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