$73 million to tackle infectious diseases such as West Nile virus and influenza

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 plague bacteria.

• 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.