NCID
BIOTERRORISM EXTRAMURAL RESEARCH GRANT PROGRAM
PROGRESS REPORT
The NCID Office of Extramural Research funded $8.4 Million in
9 Biodefense Research Grants in FY03. This report provides progress
in achieving research objectives in year one of these awards and
is organized by NCID areas of interest for bioterrorism and infectious
disease research:
- Surveillance and Epidemiology
- Interruption of Transmission
- Environmental Detection
SURVEILLANCE AND EPIDEMIOLOGY
Dr. Lawrence Glickman of Purdue University is
developing a nation wide veterinary medical disease-surveillance
operating system (VMD-SOS) to alert public health officials to
naturally occurring or man-made environmental hazards before they
would otherwise be recognized. The infrastructure for VMD-SOS is
complete and includes data transferred from >10,000 animal patients
per day in 400 hospitals located in 42 states and software programs
for data management and analysis.
Dr. Glickman successfully validated the VMD-SOS system in a pilot
study in the Washington, D.C., area for Canine Parvovirus infection.
Presentations:
“Use of the VMD-SOS for Surveillance of Veterinary Drug
Associated Adverse Events”. 2004. Food and Drug Administration
Center for Veterinary Medicine, Rockville, MD. Glickman L, Glickman
N, and Lewis H.
“Companion Animal Surveillance”.
2004. American Veterinary Medical Association Annual Convention,
Philadelphia, PA. Moore G, and Glickman L.
“Development of a National Companion Animal Syndromic Surveillance
System for Bioterrorism”. 2004. GIS Veterinary Conference,
Ontario, Canada. Moore G, Ward M, Dhariwal J, Wu C, Glickman N,
Lewis H, and Glickman L.
“Use of a Veterinary Practice Medical Database for Surveillance
of Companion Animal Syndromes and Diseases”. 2004. 22 nd
Annual American College of Veterinary Internal Medicine Forum,
Minneapolis, MN. Moore G, Ward M, Dhariwal J, Wu CC, Glickman N,
Lewis H, and Glickman L.
“The VMD-SOS Animal Disease Surveillance System”.
2003. Multi—Hazards Symposium, North Carolina Dept. Agriculture
and University of North Carolina, Research Triangle, NC. Glickman
L, Moore G, and Glickman N.
Dr.
Trish Perl of Johns Hopkins University is developing
a national syndromic surveillance system based on automated
data mining from a computerized patient record system. The
objectives are to develop and validate such a system based
on available clinical and laboratory data to accurately track
disease syndromes most consistent with the characteristics
of a bioterrorism event.
INTERRUPTION OF TRANSMISSION
Dr. Thomas Chambers of St. Louis University in
Missouri is using molecular determinants of flavivirus virulence
in humans to develop vaccines. His detailed molecular characterization
of yellow fever virus and Japanese encephalitis virus has implications
for genetic engineering of these viruses for vaccine production.
He constructed a novel chimeric virus of Japanese encephalitis
virus and dengue 2 virus that was shown to be highly protective
against fatal dengue encephalitis in a challenge model using a
mouse neuroadapted dengue 2 strain.
Publications:
Vlaycheva L, Droll DA, Nickells M, and Chambers T J. Neuroblastoma
cell-adapted yellow fever 17D: Mutagenesis of a locus involved
in persistent infection and effects on virus penetration and cell-to-cell
spread. Submitted. J. General Virology.
Vlaycheva L, Nickells M, Droll DA, and Chambers TJ. 2004. Yellow
fever 17D virus: Pseudoreversion of defective virus penetration
and spread by mutations in domains II and III of the envelope protein. Virology,
327: 41-9.
Nickells M, and Chambers TJ. 2003. Neuroadapted yellow fever virus
17D: determinants in the envelope protein govern neuroinvasiveness
for SCID mice. J. Viroloogy 77: 12232-42.
Dr.
Gary Bokoch of Scripps Research Institute is investigating the
molecular mechanisms by which Bacillus anthracis suppresses innate
human host defense mechanisms. This laboratory identified a new
mutant phenotype associated with resistance to lethal factor
action on mouse macrophages and characterization of this mutant
is underway. This laboratory also screened p22phox polymorphisms,
an essential component of NADH/NADPH oxidase, for susceptibility
to B. anthracis infections and concluded that there is no evidence for
an association of identified polymorphisms with an increased susceptibility
to infection.
Dr. Christopher Collins of SRI International is
developing new antibiotic drug candidates for use against Category
A bacterial pathogens. Dr. Collins tested over 189 compounds expanding
the structure-activity relationship data and providing the basis
for designing novel new compounds that show good antimicrobial
activity against S. pneumoniae and B. anthracisS.
aureus, E. faecalis , Y. pestis, and F.
tularensis.
Patent entitled:
Nitofuran
Antimicrobials 2004.
This
patent lists the structures of the new antimicrobial agents.
Presentations:
Mortelmans K, Tanga M, Collins C, Hokama L, and Cisneros J. Novel
nitrofuran-like antimicrobial agents against biodefense organisms.
2003. ICAAC, Chicago, Il.
Dr. Stephen Jameson of the University of Minnesota Medical
School is studying the nature of anti-viral T-cell responses
against the pox virus vaccinia to further understanding of vaccination
efficacy in immunodeficient individuals. Preliminary experiments
using vaccinia with L. monocytogenes as a control show
that mice recovering from sub-lethal irradiation can still respond
to vaccinia and Listeria infection by generation of functional
CD8 effector T-cells.
Dr. Leslie Berg at the
University of Massachusetts is studying tyrosine kinases
and the tyrosine kinase signaling pathways in anti-viral T-cell
mediated immunity. Dr. Berg has demonstrated that tyrosine kinase
deficient mice infected with Lymphocytic choriomeningitis virus
(a member of the hemorrhagic fever viruses) have a reduced T-cell
effector response and that the T-cell defects are not due to
a lack of CD4+ T-cell help.
ENVIRONMENTAL DETECTION/ENVIRONMENTAL MICROBIOLOGY
Dr. Ashutosh Chilkoti of Duke University is developing
a nanotechnology platform for real time environmental detection
of Category A pathogens. Dr. Chilkoti fabricated nano chips after
successfully synthesizing and characterizing gold nano particles.
The performance of the chips resulted in several publications.
Publications:
Nath N, and Chilkoti A. Submitted. Real-time, label-free biosensing
using gold nanoparitcles on a surface: optimization of nanoparticle
size. Anal Chem.
Nath
N, Chilkoti A. InPress. Biosensors based on metal nanoparticles. “Topics in Fluorescence Spectroscopy” Vol
8. Ed: J.R. Lakowicz. Plenum Publishers, NY.
Nath N, and Chilkoti A. 2004. Label free colorimetric biosensing
using nanoparticles. J. Fluorescence 14: 377-89.
Presentations:
Nath N, Chilkoti A. 2003. Real-time label free biosensing using
immobilized gold nanoparticles: influence of nanoparticle size
on sensor performance, 50 th AVS Intl. Symp., Baltimore, MD.
Nusz G, and Chilkoti A. 2003. Single nanoparticle detection of
biological molecules via darkfield microscopy, 50 th AVS Intl.
Symp., Baltimore, MD.
Marinakos SM, Nath N, and Chilkoti A. 2003. Label-free biosensor
based on the surface plasmon resonance of gold nanoparticles, 50
th AVS Intl. Symp., Baltimore, MD.
Dr. David Ecker of Ibis Therapeutics is completing
the development and validation of the infectious disease diagnostic
platform that was created to detect a broad range of biological
weapons agents in samples collected from the environment. The kit
is ready for laboratory validation.
Patent entitled:
Method for Rapid Purification of Nucleic Acids for Subsequent
Analysis by Mass Spectrometry by Solution Capture.
U.S. Patent Application Serial No. 10/844,938, filed on 5/12/04.
Patent Cooperation Treaty (PCT) Application Serial No. PCT/US2004/015196,
filed on 5/13/04.
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