Modulation of Burkholderia Pseudomallei Immune Responses by Human-like T cell Epitopes
Abstract
Modulation of Burkholderia pseudomallei immune responses by human-like T cell epitopes (Thrust 3) Co-PIs: Drs. Katie Edwards and Annie De Groot Topic Area: PerF-Topic 10 Project Summary Development and FDA approval of a safe and effective vaccine against Burkholderia pseudomallei (Bpm) remains an unmet Department of Defense objective for two significant reasons: weaponization of this bacterium for mass dissemination may be readily achieved by our adversaries and antibiotic therapy may be ineffective because the bacterium is naturally resistant to a broad spectrum of available antibiotics. A number of Bpm protein vaccines have demonstrated effectiveness in animal models but do not fully protect against lethal infection since this intracellular bacteria appears to have developed evasion strategies. One strategy pathogens use to evade immune responses marshals regulatory T cells (Tregs) to inhibit the protective role(s) played by other immune cell populations. Recent studies have shown that human-like protein segments in pathogens trigger Treg functions. We hypothesize that human-like segments of Bpm proteins may trigger immune cells that suppress protective responses. To address this hypothesis, we propose to use novel computational tools to rapidly discover these protein segments in promising Bpm vaccine proteins and assess their ability to stimulate immune cells obtained from human Bpm infection survivors and Bpm-infected humanized mice. We also hypothesize that recombinant DNA technology can be harnessed to modify Bpm vaccine proteins to render them better able to stimulate protective immune processes by extinguishing their Treg triggers. To lay the groundwork for this novel rational vaccine design strategy, we will evaluate human and mouse immune responses to proteins designed to disrupt Treg induction. This project will be a multidisciplinary effort involving CUBRC as the prime institution (project management), University of Florida (clinical sample procurement, mouse infections and immunoassays) and EpiVax (immunoinformatics and human immunoassays)
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Feb 09, 2017
- Source ID
- HDTRA11710014
Entities
People
- Katie A Edwards
Organizations
- Calspan-University of Buffalo Research Center
- Defense Threat Reduction Agency