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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI082642-05
Application #
8501257
Study Section
Special Emphasis Panel (ZAI1-KS-I)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2013
Total Cost
$357,583
Indirect Cost
$76,266
Name
University of Rhode Island
Department
Type
DUNS #
144017188
City
Kingston
State
RI
Country
United States
Zip Code
02881
Tomimaru, Yoshito; Mishra, Sasmita; Safran, Howard et al. (2015) Aspartate-β-hydroxylase induces epitope-specific T cell responses in hepatocellular carcinoma. Vaccine 33:1256-66
Terry, Frances E; Moise, Leonard; Martin, Rebecca F et al. (2015) Time for T? Immunoinformatics addresses vaccine design for neglected tropical and emerging infectious diseases. Expert Rev Vaccines 14:21-35
Liu, Rui; Moise, Leonard; Tassone, Ryan et al. (2015) H7N9 T-cell epitopes that mimic human sequences are less immunogenic and may induce Treg-mediated tolerance. Hum Vaccin Immunother 11:2241-52
Becker, Martin; Felsberger, André; Frenzel, André et al. (2015) Application of M13 phage display for identifying immunogenic proteins from tick (Ixodes scapularis) saliva. BMC Biotechnol 15:43
Losikoff, Phyllis T; Mishra, Sasmita; Terry, Frances et al. (2015) HCV epitope, homologous to multiple human protein sequences, induces a regulatory T cell response in infected patients. J Hepatol 62:48-55
De Groot, Anne S; Ross, Ted M; Levitz, Lauren et al. (2015) C3d adjuvant effects are mediated through the activation of C3d-specific autoreactive T cells. Immunol Cell Biol 93:189-97
Eickhoff, Christopher S; Van Aartsen, Daniel; Terry, Frances E et al. (2015) An immunoinformatic approach for identification of Trypanosoma cruzi HLA-A2-restricted CD8(+) T cell epitopes. Hum Vaccin Immunother 11:2322-8
Pichu, Sivakamasundari; Ribeiro, Jose M C; Mather, Thomas N et al. (2014) Purification of a serine protease and evidence for a protein C activator from the saliva of the tick, Ixodes scapularis. Toxicon 77:32-9
Shattuck, Wendy M C; Dyer, Megan C; Desrosiers, Joe et al. (2014) Partial pathogen protection by tick-bite sensitization and epitope recognition in peptide-immunized HLA DR3 transgenic mice. Hum Vaccin Immunother 10:3048-59
Zhang, Songhua; Desrosiers, Joseph; Aponte-Pieras, Jose R et al. (2014) Human immune responses to H. pylori HLA Class II epitopes identified by immunoinformatic methods. PLoS One 9:e94974

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