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Overview of the Biological Systems theme

Vaccines, anti-virals, detection/diagnostic tests, and universal platforms that satisfy Department of Homeland Security goals of detection, diagnosis, prevention and recovery

UTMB BSL labOverview:  Targeted deliverables of FAZD Center Biological Systems (BioSys) research include improved methods for detection, diagnosis, and immunization, as well as expanding the understanding of the molecular basis for host-pathogen interactions during infection and resistance.  The FAZD Center development and implementation of new technologies and capabilities have been successfully linked to six national laboratories keenly focused on four representative diseases which will provide broad, flexible platforms applicable to many forms of animal bioterrorism.  The molecular basis for the biology of disease processes (Pathomics) with global gene expression and proteomic analyses have now been implemented in vitro and in vivo for both livestock host and select agent pathogen in FAZD Center laboratories, and vast databases have been created to be mined by bioinformatics and computational biology to identify host “biosignatures” and pathogen “biomarkers” in order to improve diagnostics and vaccines.  The deliverables in DHS priority areas will also serve as important information resources for enhanced disease modeling so that the impact of these deliverables can be estimated in terms of prevention, detection, response, and recovery from agrobioterrorist events.

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The Biological Systems team focuses on three primary diseases:

  • FMD (foot and mouth disease) -- The first short-term priority for Foot and Mouth Disease (FMD) research is to expand surge diagnostic capacity in the National Animal Health Laboratory Network (NAHLN) by developing eukaryotic cell lines persistently replicating sub-genomic replicons of FMD virus under BSL2 conditions as a safe, killed antigen source for mass scale robotics-based ELISA FMD antibody detection.  In a priority project, Baculovirus-expressed FMD viral antigens is used to stimulate and select high affinity monoclonal antibodies to detect FMD antigen in “chute-side” lateral flow immunoassays for use by field personnel.  Longer-term prevention and recovery deliverables are aimed at identifying anti-FMD virus compounds and identifying bovine innate FMDV resistance genes.
  • cdcpatient.jpgAvian influenza -- The first short-term priority of the Avian Influenza projects is to develop methods to detect Avian Influenza virus (AIV) and anti-AIV antibodies that are highly sensitive and specific immune-based (lateral flow immunoassay, ELISA and particle-based multiplex flow cytometry) and Real-Time-PCR nucleic acid-based assays for immediate application.  The intent is to deploy these assays to National Animal Health regional HUB laboratories and/or poultry production units to expedite diagnosis of AI exposure by detecting the virus or antibodies in poultry or waterfowl specimens.  The second longer-term priority of the AI research is to develop safe and efficacious vaccines and explore the use of immunomodulators to enhance innate and acquired AI resistance at population levels.  By developing protective recombinant vaccines with DIVA properties, the intent of the vaccine research is to circumvent the issue of confusing the diagnosis of wild type AI infections with the immune response stimulated by inactivated-, viral vectored-, or DNA-based vaccines to prevent, respond, and recover from AI events.  The last intermediate-term priority of AI research is to characterize in detail the US live bird market (LBM) system as an important source of influenza virus infection for commercial poultry and mammalian populations.  The intent of these investigations is to provide documented data as the substrate for sound epidemiologic modeling of the behavior of AI virus across marketing schemes and cultures, developing educational outreach materials and establishing the scientific basis for sound AI control policies in poultry and mammalians, including swine and humans.
  • Rift Valley fever -- A short-term priority of the Rift Valley Fever (RVF) projects is to develop and evaluate Real-Time PCR assays to detect RVF virus, and IgM and IgG ELISA tests for detecting antibodies during acute and subacute to chronic RVF viral infections respectively using RVF MP-12 vaccine strain or baculovirus-expressed recombinant RVF protein antigens.  The intent is to produce the reagents under BSL2 conditions for deployment in the regional National Animal Health Laboratory Network.  The second intermediate-term RVF research priority is to develop effective and rapidly acting RVF vaccine candidates by applying state-of-the-art molecular biology tools coupled with evaluation of immunogenicity and safety in laboratory animals and sheep.  The intent is to enable mass-scaled production and stockpiling the RVF vaccine under BSL2 manufacturing conditions for prevention, response, and recovery.  Lastly, the longer term RVF research priority is to explore functional innate genetic resistance to RVF virus in laboratory rodents for ultimate application in ruminants as a deterrent to bioterrorists employing this pathogen as a WMD.

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Leading products

  • Vaccines for RVF and AI: There is a critical need for improved vaccines for zoonotic diseases of economic and public health applications, such as Rift Valley Fever (RVF) and Avian Influenza (AI). In addition to safety, efficacy, and the ability to manufacture sufficient quantities of vaccine, FAZD Center investigators are using modern recombinant technologies to incorporate genetic “markers” into RVF and AI vaccines to make it possible to distinguish vaccinated livestock from infected livestock. In an outbreak, this property will prevent unnecessary slaughter of animals and avert further damage to the economy through trade restrictions. It will also lessen challenges to the capacity for carcass disposal. Candidate vaccines are ready for initial field testing.
  • Anti-Viral Protection Against FMD (with Plum Island Animal Disease Center): Standard vaccines for FMD require up to 10 days before becoming effective, creating an immunity gap during which livestock remain vulnerable to one of the most contagious of viral diseases. A new antiviral from the FAZD Center promotes “natural killer cells” that attack the FMD virus, providing protection within three days.  Research in this area contributes to vaccine development at Plum Island Animal Disease Center.
  • Commercial Production of RVF Vaccine – MP-12 : A major pharmaceutical company has approached the University of Texas Medical Branch – a partner in the FAZD Center – to support the development of a commercial vaccine for Rift Valley fever using the MP-12 antigen which is also being considered for development of a human vaccine.  The FAZD Center has supported the development of an animal vaccine at UTMB for three years.  This is a major step towards successful technology transfer for a product that can either become part of the national veterinary stockpile or be commercialized for international use. If the decision to proceed is taken, the initial development cycle would require about one year.
  • Rapid Detection Tests: After an outbreak of Foot and Mouth Disease (FMD) has been confirmed, the emergency response program to eradicate the disease involves sometimes massive culling of infected or exposed herds. The FAZD Center is developing rapid, accurate, inexpensive field tests that will distinguish between infected and uninfected animals at chute site within minutes.  This will eliminate unnecessary loss of uninfected animals, saving hundreds of thousands of animals in large outbreaks.
  • Integrated Platforms for Unknown or Attenuated Disease Agent Characterization: Pathogens encountered in the future may differ substantially and in unknown ways from those identified and characterized today, either by natural or intentional attenuation. To address this gap, the FAZD Center is developing with its partners a suite of universal, unbiased, and massively parallel micro- and nano-analytical devices that can collect, compare, and archive genetic biosignature information to effectively categorize and contribute to the development of strategies for outbreaks of unknown etiology. This suite of technologies includes the Integrated Biomarker Specific Biosignature (IBSB), Multiple Select Agent Specific (MSAS), and Universal Biosignature Detection Array (UBDA) platform technologies.

 

Project reports (most recent)