The long-term objective of this proposal is to develop a new immunotherapeutic approach towards demyelinating EAE in a non- human primate. To achieve this long-term goal the following specific aims will be pursued: (1) Characterization the IgG1 VH and VL kappa repertoire in C. jacchus. Using the PCR based method RACE and subsequent DNA sequencing will permit the identification of C. jacchus IgG1 H and L chain subfamilies. (2) Analysis of the diversity of the antibody response against myelin proteins in C. jacchus. By constructing a combinatorial F(ab) library from C. jacchus IgG mRNA it will be possible to select MOG and MBP specific clones and to describe the diversity IgG1 VH and VL kappa usage in the antibody response to these myelin proteins. (3) Production of soluble MOG-and MBP-specific F(ab) fragments to be administered in MOG immunized C. jacchus to prevent demyelination. The removal of the gIII protein from the phage clones selected for high affinity binding to MOG or MBP, will permit the expression of soluble F[ab] fragments. High affinity MOG specific F[ab] will be tested in their ability to prevent demyelination in marmoset EAE. MBP specific F[ab] will be used as control. If this immunotherapeutic approach proves to be successful, therapies based on similar principles could be developed for human MS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS010996-02
Application #
6187646
Study Section
Special Emphasis Panel (ZRG1-BDCN-2 (02))
Program Officer
Kerza-Kwiatecki, a P
Project Start
2000-09-28
Project End
Budget Start
2000-09-28
Budget End
2001-09-27
Support Year
2
Fiscal Year
2000
Total Cost
$40,936
Indirect Cost
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143