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

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

Collaborating Institution: Baylor College of Medicine (BCM), Houston, TX

Principal Investigator: George M. Weinstock, Ph.D.

Co-Investigators:
a) Timothy G. Palzkill, Ph.D., BCM, Houston, TX
b) Joseph Petrosino, Ph.D., BCM, Houston, TX
c) Orna Resnekov, Ph.D., Molecular Sciences Institute, Berkeley, CA.
d) Ian Burbulis, PhD- Molecular Sciences Institutee, Berkeley, CA.

Expected Product: Diagnostics for tularemia.

Description: Francisella tularensis, the causative agent of tularemia, is one of the most infectious bacteria known and is a Category A biodefense concern. Diagnostic tools that detect Francisella and other select agents are among the critical needs identified by the NIH/NIAID that are targeted for immediate development and are the focus of this proposal. Two key components of a successful diagnostic are a high-affinity sensor domain that binds directly to the targeted organism, or to a product secreted by the organism, and a signal domain that indicates when the sensor has bound the target molecule. We will use proven technologies: single-chain variable domain antibody fragment- (scFv-) phage-display, tadpole protein-DNA chimeras, real-time PCR and the results from our antigen discovery research to create powerful diagnostics that will detect the presence of Francisella tularensis (Ft) in biological and environmental samples as well as immune responses directed against Ft. These tools will be able to amplify a binding signal so that detection will be at least >100-fold more sensitive than what is possible using Enzyme-Linked Immunosorbent Assay (ELISA). Furthermore, these diagnostics will be able to identify target molecules over a wide dynamic range of concentrations. This strategy can be applied to the development of diagnostic reagents that recognize any given target and could lead to a pipeline that generates sensitive diagnostic tools for many biodefense/infectious disease pathogens.

The bacterium that causes tularemia is one of the most infectious agents known and is a serious biodefense threat. Greatly needed are tools that can detect minute quantities of the organism and/or that can detect whether a person has been infected by the organism early in the course of infection. We will use cutting-edge strategies to create molecules that can identify tiny amounts of the organism and that provide a sensitive readout as to the presence or absence of the organism using a common assay. The strategies used to create this powerful tool can easily be adapted to create similar reagents for any biodefense or infectious disease concern.