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
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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.
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