To meet the dual threats of emerging infectious diseases and engineered biowarfare/bioterror agents, there is a pressing need for more efficient systems for vaccine development. TRIAD, or the Translational Immunology Research and Accelerated [Vaccine] Development program, based in the Biotechnology Program at the University of Rhode Island, has pioneered the development and application of an integrated """"""""gene to vaccine"""""""" in silico, in vitro and in vivo vaccine design program to address this need. TRIAD has selected Category A pathogens F. tularensis, Category B agents Burkholderia pseudomallei and Burkholderia mallei, and emerging infectious diseases (HCV, H. pylori, tick borne diseases) as the focal point of this proposal. Using the TRIAD immunoinfomatics Toolkit, TRIAD investigators will pursue the development of second generation epitopebased immunome-derived vaccines for these pathogens, while addressing the failings of prior generations of epitope based vaccines. We will maximize payload quantity using validated immunoinformatics tools that permit selection of optimal T cell epitopes that are highly conserved and immunogenic. We will ensure payload quality by choosing epitopes that demonstrate antigenicity in human PBMC as well as protection in established murine models of disease/infection. We will select a combination of promiscuous Class II epitopes and Class I supertype epitopes will provide >99% coverage of human populations. We will avoid cross-reactive epitopes and explore the role of regulatory T cells in the context of improving vaccine design. Where appropriate, we will combine our epitope-driven vaccines with broad-spectrum anti-LPS vaccines. We will optimize payload, delivery, formulation, and adjuvanting by exploring a range of delivery options [Dendritic cells, DEC205, DNA, electroporation, mucosal delivery). The TRIAD project aims to develop vaccines demonstrating broad spectrum activity include crossprotective and multiple component vaccines, and delivery technologies that have the potential to be effective against multiple emerging and re-emerging infectious diseases. Our efforst to merge rational design with rcentadvances in vaccine deliverywill manifest in a coordinated toolkit and a cadre of informed users, who will be ready and able to apply the tools to discover new treatments for emerging infectious disease and biodefense.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-KS-I)
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University of Rhode Island
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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
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
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
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
Tomimaru, Yoshito; Mishra, Sasmita; Safran, Howard et al. (2015) Aspartate-?-hydroxylase induces epitope-specific T cell responses in hepatocellular carcinoma. Vaccine 33:1256-66
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
Mishra, Sasmita; Losikoff, Phyllis T; Self, Alyssa A et al. (2014) Peptide-pulsed dendritic cells induce the hepatitis C viral epitope-specific responses of naïve human T cells. Vaccine 32:3285-92
Bailey-Kellogg, Chris; Gutiérrez, Andres H; Moise, Leonard et al. (2014) CHOPPI: a web tool for the analysis of immunogenicity risk from host cell proteins in CHO-based protein production. Biotechnol Bioeng 111:2170-82
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

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