Thursday, August 25

7:30-8:15 Breakfast Technology Workshop

Sponsored by

Anthrax, Brucellosis, Cholera... ­ the ABC of Biopathogen Detection Prenanalytics Dr. Helge Lubenow, Director R&D Nucleic Acid Purification, QIAGEN GmbH  Successful implementation of efficient biodefense surveillance systems depend on several critical factors. Effective and reliable methods for sample collection, isolation, detection and identification of potentially pathological agents are crucial. Standardized systems characterized by a simple uniform workflow ensure minimal operator training, and increase process safety and reliability. Flexible automation systems further increase efficacy, avoid any sample-to-sample variation and minimize human contact to minimize operator risk. We will present several processes suitable for isolation and purification of nucleic acids from a range of different bacterial and viral agents. Also presented are dedicated technologies for highly specific amplification and detection of both DNA and RNA based assays. Potential impact of emerging technologies such as whole genome amplification will be discussed.

8:00-8:30 Coffee

MEETING THE NEEDS OF THE INDUSTRY:
VALIDATION OF SYSTEMS

8:40-9:10 Rapid Assays for Biothreat Agent Detection for Public Health Laboratories
Dr. Richard F. Meyer, Director, Bioterrorism Rapid Response & Advanced Technology Laboratory, Centers for Disease Control & Prevention 
In a bioterrorism event, our ability to rapidly detect and confirm the identity of the agent and communicate the results will determine the effectiveness of the public health response. That is why standardized validated assays that produce high confidence results are essential for public health response and decision making.

9:10-9:40 TBA

9:40-10:10 Requirements within the Department of Defense
LTC Mark Bohannon, Joint Requirements Office, JRO-CBRN Defense

10:10-10:45 Coffee Break, Poster & Exhibit Viewing

HANDS-ON TECHNOLOGY WORKSHOP

11:00-11:30 Gene-Expression Biomarkers for Application to High-Throughput Radiation Biodosimetry
Dr. Mary Beth Grace, Principal Investigator, Armed Forces Radiobiology Research Institute Molecular biodosimetry tools are a valuable asset for life-saving medical triage and patient management following a radiological or nuclear disaster. Even with the delayed onset of symptoms, sometimes several days after exposure, gene-expression biomarkers can identify these exposed individuals very early after exposure, allowing for prompt medical intervention. This early assessment of a radiation dose after exposure would enhance the operational commander’s situational awareness of the radiation exposure status of deployed units and increase the prospect of reduced morbidity and mortality through early medical intervention. Candidate gene targets were selected from microarray studies of ex vivo-irradiated human peripheral blood lymphocytes and measured using a quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) assay in a human whole blood model at 24 and 48 hr post-irradiation (0.2 to 5.0 Gy 60Co-gamma rays at 0.1 Gy/minute). A multi-target QRT-PCR technique was optimized, an inter-individual variation study of an ex vivo response was expanded to include a larger cohort of healthy donors, and a collaborative study was conducted involving the in vivo response of cancer patients undergoing total body irradiation treatment. These validation studies illustrated that gamma radiation causes quantifiable and reproducible gene-expression changes in the radiation biomarker targets CDKN1A, BAX, GADD45A, and DDB2 over several days across a broad dose range in both in vivo and ex vivo models. However, further validation studies are required before these gene targets can be used as molecular biodosimeters. Once validated, the gene-expression signatures of several sentinel biomarkers would provide an early dose estimate that would then be used when making decisions involving personnel operational capabilities and/or clinical therapy. In addition, we are implementing validated protocols for automation to create high-throughput clinical and deployable PCR-based diagnostic platforms. With the increased throughput, the use of the Armed Forces Radiobiology Research Institute’s Biodosimetry Assessment Tool (BAT), and a multi-parameter biodosimetry diagnostic.

11:30-11:45 HANDS-ON TECHNOLOGY WORKSHOPS (sponsorship available)

11:45-1:00 Lunch on your own (Technology Workshop Sponsorship Available) 

BIODEFENSE THERAPEUTICS

1:00-1:10 Chairperson
Dr. Sandy Weinberg, Senior Director, GE Healthcare 

1:10-1:45 Current Directions in Biodefense Vaccine and Therapeutic Development
Darrell R. Galloway, Ph.D., CAPT USNR, Capability Area Program Officer, Joint Science & Technology Office - CBM, Defense Threat Reduction Agency
This presentation will cover an overview of program objectives as they stand today; give an update on the status of current projects; explain future directions - emerging technologies and underlying issues; as well as discuss current and future challenges. The objective of the talk will be to provide a comprehensive overview of the technologies being applied toward the development of new vaccines and therapeutics within the biodefense scientific community. Also to be presented will be a discussion of the challenges faced in order to bring such approaches to product development.

1:45-2:15 Future Challenges of Medical Countermeasures Against Biothreat Agents
Dr. Thomas M. Dreier, Director, Battelle BioSystems 
Future medical countermeasures for biological threat agents require that the medical community start to think about new approaches to protecting personnel at risk. Current vaccination and antibiotic therapy approaches have been designed to combat infectious disease. However, vaccines generally must be delivered prior to exposure and may be ineffective against genetically modified threats. Antibiotics may be effective against only certain strains and generally are not effective against viruses or toxins. Future biothreat countermeasures must overcome these drawbacks and must be acceptable to a diverse population, deliverable to at-risk populations, and must offer broad spectrum protection. This presentation will evaluate options for the development of new medical countermeasure.

2:15-2:45 Intranasal Delivery of Vaccines for Biodefense
Dr. Vincent Sullivan, Group Leader/Senior Scientist, Advanced Drug Delivery, BD Technologies 
Anthrax vaccine based on recombinant protective antigen (rPA) has been formulated as a dry powder and delivered intranasally in animal models using a novel, disposable, unit dose powder delivery device. In work conducted by BD in collaboration with USAMRIID, rabbits exposed to a lethal dose of inhalation anthrax after nasal immunization with the powder showed an 83 to 100 percent survival rate, similar to the protection offered by the injectable formulation. Initial data indicates that the powdered formulation of rPA is also more stable than a liquid version and can withstand wider temperature extremes.

2:45-3:15 Construction and Exploitation of Pathogen ORFEOME Collections
Dr. Tallamraju Murthy, Research Associate, Proteomics, Harvard Medical School
Genome sequencing projects have produced an immense amount of information regarding the organization, evolution and coding 
capacity of a large number of bacterial genomes. There is an ever-increasing need to develop tools and resources that can build on the genome information and facilitate the understanding of the biological function and involvement of every ORF in the different aspects of host-pathogen interactions. Comprehensive analysis of protein function, protein-protein interactions, and role of pathogen-encoded proteins in host pathogen interactions (including immunogenicity), have been limited by the availability of state-of-the-art resources. I will describe the construction of comprehensive ORFeome collections for Yersinia pestis, Francisella tularensis, Bacillus anthracis and Pseudomanonas aeruginosa. I will also describe the use of the clones in high-throughput protein expression and purification to study their contribution to the humoral and cellular immune response of the host and to identify vaccine candidates.

3:15-3:45 Refreshment Break, Poster & Exhibit Viewing

3:45-5:00 Expediting the Development of Biodefense Solutions  • Barriers and specific solutions to speedy development of biodefense detection systems and vaccines Thioaptamers for Proteomics and Therapeutics in Biodefense Dr. David Gorenstein, Chairman, Therapeutics and Diagnostics, AptaMed, Inc. RNA and DNA oligonucleotides can act as "aptamers," (i.e., as direct in vivo binders selected from large combinatorial libraries) for a number of proteins. We have recently developed both in vitro enzymatic combinatorial selection and split-synthesis chemical combinatorial methods to identify phosphorothioate-modified oligonucleotide "thioaptamers" to a number of different infectious disease protein targets for both diagnostics and therapeutics. We are also developing thioaptamer chips for identifying these proteins with mass spectrometric methods. We believe that these methods will provide an important diagnostic tool to identify and quantify the differential expression of key proteins in response to pathogens of concern for the bioterrorism threat. We demonstrate that selected thioaptamers can also modulate the immune response and show promise as therapeutic agents targeting viruses such as West Nile virus and hemorrhagic fever arenaviruses. Challenges and Strategies for Financing Early-Stage Biodefense Companies Dr. Chad Womack, CEO & Chief Scientific Officer, NanoVec, LLC Developing vaccines and immunotherapeutics to address the nation's biodefense needs will require full engagement of the private sector, particularly biotechnology companies. Platform-based biotechnology companies are uniquely poised to provide innovative solutions to the many public health challenges that bioterrorism presents. While the biodefense sector represents a unique 'proving ground', particularly for those companies developing technologies that can address multiple markets, the biodefense market remains uncertain and lacking guidance regarding federal guarantee for procurements and contracts. Therefore, in attempting to address this uncertain market, early-stage companies such as NanoVec, continue to face significant challenges in developing appropriate business models, R&D programs and successful financing strategies. Some strategies that we have developed to address these issues will be highlighted.  A Model for Overcoming Barriers to Development Dr. Sandy Weinberg  The rapid progress of biodefense vaccines and detection systems from laboratory to market requires anticipation, avoidance, and/or coping with a series of hurdles. These barriers include grant funding, patent protection, preclinical and clinical testing, regulatory approvals and monitoring, pilot production development, commercialization, licensing, full scale production design, and distribution. This presentation reviews those nine potential challenges, presents a model for planning to meet those challenges, and focuses specifically on sources of initial grant funding sources, processes, and assistance. The 122 current US government biodefense grant programs will be summarized; twelve private and international grant alternatives will be reviewed; and strategic recommendations for increasing the odds of securing funding are provided.

5:00 Close of Conference