NIAID Launches Program to Improve Medical Tools
Against Emerging Infectious Diseases
The National Institute of Allergy and Infectious Diseases (NIAID),
part of the National Institutes of Health (NIH), has awarded 14
contracts totaling more than $73 million to fund the Large-Scale
Antibody and T Cell Epitope Discovery Program, an initiative aimed
at quickly identifying the regions of selected infectious agents
that elicit immune reactions. The study of these regions, known
as epitopes, promises to uncover targets for new and improved vaccines,
therapies and diagnostic tools against potential bioterror agents
as well as emerging/re-emerging infectious diseases such as West
Nile virus and influenza. NIAID will make information on each newly
identified epitope freely available to scientists through a searchable
online database currently under development.
“Elucidating the basic mechanisms of immune function is a major
focus of our biodefense research agenda,” says Anthony S.
Fauci, M.D., director of NIAID. “The information generated
by this program will deepen our understanding of how components
of the immune system defend against certain infectious agents,
enabling researchers to design new and improved medical countermeasures.”
“Researchers have been conducting epitope discovery for many years,
but generally on a small scale,” says Daniel Rotrosen, M.D.,
director of NIAID’s Division of Allergy, Immunology and Transplantation. “This
initiative, however, will yield new knowledge about antigenic epitopes
from a wide variety of microbes, including agents that might be
used in a bioterrorist attack.”
Epitopes are recognized by the body’s B and T cells, white
blood cells that detect an invading pathogen. Each B and T cell
is specific for a particular antigen, meaning that each can only
bind to a certain foreign molecular structure. This “specificity” is
determined by the receptors on the surface of each cell.
Both B- and T-cell specificity as well as the diverse functions
of these cells determine the effectiveness of an immune response.
B cells produce antibodies, which bind to target antigens at their
epitopes, eliminating the pathogens before infection can spread
or marking them for destruction by other cells. T cells either
destroy infected target cells, control inflammation or promote
powerful antibody responses.
The Large-Scale Antibody and T Cell Epitope Discovery Program will
increase knowledge of antibody and T-cell epitopes, which will
facilitate the development of new medical tools to detect, prevent
and treat infectious diseases. The institutions involved in the
program and the principal investigator at each are
- The Scripps Research Institute, La Jolla, CA, Kim Janda,
Ph.D. Focus: antibody epitopes of botulinum toxin.
- Benaroya Research Institute at Virginia Mason, Seattle, WA, William Kwok, Ph.D.
Focus: T-cell epitopes of influenza viruses as well as anthrax and tetanus bacteria.
- La Jolla Institute for Allergy and Immunology, San Diego, CA, Alessandro Sette, Ph.D.
Focus of first contract: T-cell epitopes of arenaviruses, such as Lassa fever. Focus of second contract: T-cell epitopes of smallpox viruses.
- University of Oklahoma Health Sciences Center, Oklahoma City, William Hildebrand, Ph.D. Focus: T-cell epitopes of influenza viruses, West Nile virus and the Q fever bacterium.
- Duke University, Durham, NC, Kent Weinhold, Ph.D. Focus: T-cell epitopes of the Ebola virus and the bacteria that cause multi-drug resistant tuberculosis.
- Imperial College, London, England, Daniel Altmann, Ph.D. Focus: T-cell epitopes of anthrax and
- Johns Hopkins University, Baltimore, MD, J. Thomas August, M.D. Focus: T-cell epitopes of microbes that cause hantavirus pulmonary syndrome, dengue fever, yellow fever and other diseases.
- University of North Carolina, Chapel Hill, Jeffrey Frelinger, Ph.D. Focus:
T-cell epitopes of the tularemia bacterium.
- Vanderbilt University, Nashville, TN, Sebastian Joyce, Ph.D. Focus:
T-cell epitopes of smallpox viruses.
- Torrey Pines Institute for Molecular Studies, San Diego, CA, Clemencia Pinilla,
Ph.D. Focus: T-cell epitopes of smallpox viruses.
- Oregon Health and Science University, Portland, David Lewinsohn, M.D., Ph.D. Focus: T-cell epitopes of the bacteria that cause multi-drug resistant tuberculosis.
- University of Copenhagen, Denmark, Soren Buus, Ph.D. Focus: developing mathematical tools that
more accurately predict the location of T-cell epitopes in genomes of potential agents of bioterrorism.
- Centre for Biological Sequence Analysis at the Technical University of Denmark, Ole Lund, Ph.D. Focus: developing mathematical tools that more accurately predict the location of T-cell epitopes in
genomes of potential agents of bioterrorism.
Almost all of the institutions will evaluate newly discovered epitopes
in preclinical or clinical studies, where feasible, for their capacity
to elicit immune responses. For a list of NIAID category A, B and
C biodefense pathogens, visit http://www2.niaid.nih.gov/Biodefense/bandc_priority.htm.
NIAID is a component of the National Institutes of Health, an agency
of the U.S. Department of Health and Human Services. NIAID supports
basic and applied research to prevent, diagnose and treat infectious
diseases such as HIV/AIDS and other sexually transmitted infections,
influenza, tuberculosis, malaria and illness from potential agents
of bioterrorism. NIAID also supports research on transplantation
and immune-related illnesses, including autoimmune disorders, asthma
and allergies. News releases, fact sheets and other NIAID-related materials are
available on the NIAID Web site at http://www.niaid.nih.gov.