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Abstract
Grant Number: 1R43AI055196-01 PI Name: LEDIZET, MICHEL E. PI Email: l2dx@aol.com PI Title: Project Title: Therapeutic Activity of a Novel Tick Immunosuppressant Abstract: DESCRIPTION (provided by applicant): The overall objective of this proposal is to evaluate the therapeutic potential of a novel immunosuppressant protein produced by tick salivary glands. Ixodes scapularis, the black-legged tick, circumvents the host's immune response by multiple mechanisms as it obtains its blood meal. Salp 15 is a protein identified by screening a tick salivary gland cDNA library. Recombinant Salp 15 inhibits the proliferation and activation of CD4+ T cells in vitro, and is also active in vivo. However, recombinant Salp 15 is less active than the native form of the protein found in saliva. In phase I experiments, the primary structure of native Salp 15 will be determined. This information will be used to synthesize a new form of recombinant Salp 15 whose amino acid sequence matches precisely that of the native protein. The activity of this new recombinant protein will be determined in vitro and in vivo. Milligram amounts of this new recombinant Salp 15 suitable for use in animals will be purified. The activity of this protein will be tested in an animal model of human disease, namely murine Lyme arthritis. In Phase II experiments the activity of Salp 15 will be tested in additional animal models of human disease.
Thesaurus Terms:
Ixodes, host organism interaction, immunosuppressive, nutrient intake activity, peptide chemical synthesis, pharmacokinetics, recombinant protein
Lyme disease, autoimmune disorder, biotherapeutic agent, disease /disorder prevention /control, helper T lymphocyte, immunoregulation, leukocyte activation /transformation, nonhuman therapy evaluation, protein structure function, saliva
SDS polyacrylamide gel electrophoresis, biotechnology, immunoprecipitation, laboratory mouse, laboratory rabbit, mass spectrometry, matrix assisted laser desorption ionization, polymerase chain reaction, western blotting
Institution: L2 DIAGNOSTICS, LLC BOX 8175 NEW HAVEN, CT 94904 Fiscal Year: 2003 Department: Project Start: 15-JUL-2003 Project End: 14-JUL-2004 ICD: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES IRG: ZRG1