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Publication Date - 12/3/1999

4. NIH - Basic and Clinical Research on Immune Tolerance

The National Institutes of Health (NIH) invites applications that will elucidate basic mechanisms responsible for inducing and maintaining antigen-specific immune tolerance, that will facilitate translation of experimental knowledge on immune tolerance into clinical therapies for the treatment or prevention of immune-mediated disease, or that will promote more effective development of vaccines by preventing pathogen-induced immune tolerance. Multidisciplinary research focused on the understanding and/or modulation of antigen-specific immune tolerance mechanisms is sought.

Immune tolerance is highly relevant to a wide range of clinically important applications. The immune system is uniquely characterized by its highly diverse and clonally expressed repertoire of lymphocyte receptors that can recognize a very broad spectrum of both foreign and self antigens. It is important to define the molecular mechanisms that determine whether antigen recognition results in anergy or apoptosis rather than effector or memory cell generation, and to identify genetic factors that regulate these mechanisms. Very productive basic research in immunology and other fields of study has provided unprecedented opportunities for clinical breakthroughs in this area, due to identification of relevant molecular pathways, new technologies, new reagents and animal model development for in vivo studies.

Both basic and clinical research projects are encouraged, but clinical trials will not be supported through this announcement. Specific examples of research areas of interest include, but are not limited to, the following:

• specific immune tolerance mechanisms in human lymphocytes, and novel experimental approaches to define such mechanisms;
• animal models to study tolerance to transplanted allogenic or xenogeneic lymphoid tissues for application to immune replacement in HIV disease;
• loss of self-tolerance due to antigen crossreaction during infection or vaccination;
• development of technologies to study tolerance vs. immunity at the single cell level to identify mechanisms or immune markers in vivo;
• tolerogenic approaches for the primary prevention of asthma and the treatment of allergies;
• analysis of tolerance induction in neonates and in aged individuals;
• protocols to induce vector-specific tolerance prior to vector-mediated vaccine delivery or gene therapy.

Mechanisms of support are the NIH research project grant (RO1) and FIRST (R29) applications with requests up to five years of support.

Application are due at the NIH Center for Scientific Review on or before FEBRUARY 1, JUNE 1,or OCTOBER 1, 2000.

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