Major Research Projects
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Abstract for the RCE

Bacillus anthracis Host Interactions

Discovery of Subunit Vaccine Candidates                             against Glanders

Alphavirus Vaccines for Biodefense

Novel Genetic Tools for Viral Biodefense

Development and Evaluation of Human
                     Brucellosis Vaccines

Rapid Diagnostic Tools for Q Fever

New Diagnostic Methods for Accute Rickettsial
                      Infections

Risks and Interventions for Pandemic Influenza

Development of Novel Pseudoinfectious Flavivirus                             Vaccines

Development of Diagnostic Reagents for the detection
                            of Francisella and
                             Francisella Infection

Toward Control of Rift Valley Fever Virus
                             Replication

Novel Vaccine Technology for Biodefense

Nucleocapsid-specific Small Molecule Inhibitors
                             of the Bunyaviridae

New Technologies for Creating Affinity Reagents

New Opportunities Projects

Identification and Characterization of Novel
                             Flavivirus Antivirals

Biosafety Containment Training Program

Passive Immunotherapeutics for
                             Select Agents

Preclinical Testing of YF17D/LAS, a Bivalent
                              Vaccine for Lassa and
                             Yellow Fever

 

New Technologies for Creating Affinity Reagents

 

Collaborating Institution: Arizona State University (ASU), Tempe, AZ

 

Principal Investigator: Stephen Johnston, PhD

 

Expected Product: Development of synthetic antibodies for a number of biodefense agents.

 

Description: This project was originally funded as the Pathogenesis Expression Core, whose purpose was to provide: (1) microarrays for select agents expression analysis and technical support, (2) antibodies for select agent proteins, and (3) technology development for expression analysis. These technologies were to aid researchers developing vaccines, therapeutics and diagnostics for select agents. In accordance with these aims we have developed and validated microarrays for Yersinia pestis, Brucella, Bacillus anthracis, and Mycobacterium tuberculosis. All four classes of arrays have been used. We have made available and refined programs to aid in performing and analyzing microarray experiments. Most notably we have improved the Genome Directed Primers program and assisted researchers in using it. We have produced antibodies to approximately 50 select agent proteins.

 

In addition, we have used some of the Core support to develop a new approach to making synthetic antibodies. The technique involves screening for combinations of peptides that bind the target protein. This system looks promising for development of synthetic antibodies that could be used in an array format, and would be faster to produce and much less expensive. These peptides can also be used to “signature” the serum in response to vaccination or infection.

 

Based on the progress with this technology, we propose to transition the Core to a research effort. We will still provide the microarray service to the WRCE research community on a per-cost basis. The major effort will be towards exploiting the new technologies for diagnostic, therapeutic and vaccine production. Specifically, we will: 1) improve the ability to make synthetic binding agents to host factors on an array format, 2) implement the technology as a high throughput system demonstrating the ability to make affinity agents to 100 proteins, and 3) apply this system to make affinity therapeutics to viruses.