: Monoclonal antibodies (MAbs) have revolutionized the conduct of science since their first description in 1975. The use of these specific reagents also has made possible improved clinical diagnostics in the medical arena, and a few antibodies have found their way to clinical use as prophylactic or therapeutic agents. Nevertheless, the potential of MAbs for therapy remains largely unfulfilled. The principal reason for the lack of a large number of MAb therapeutics is simply the difficulty in generating human monoclonal antibodies of high affinity. The objective of this proposal is to develop novel methods for the rapid and efficient generation of human B cell hybridomas secreting antibodies of medical importance. The work will develop and employ new approaches to rare antigen-specific B cell sorting from memory cell populations, and will result in the design and manufacture of new cell-cell electrofusion hardware and protocols.
Three specific aims are proposed: 1) To develop high-throughput methods for antigen-specific human B cell physical sorting and expansion; 2) To develop novel electrofusion devices and protocols that yield a high frequency of viable human hybridomas: 3) To develop high affinity neutralizing antibodies to respiratory syncytial virus, a medically important viral pathogen amenable to MAb prophylaxis, as a demonstration of the feasibility of making important antiviral antibodies using the novel techniques and equipment developed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI048677-04
Application #
6941629
Study Section
Special Emphasis Panel (ZRG1-SSS-4 (10))
Program Officer
Gondre-Lewis, Timothy A
Project Start
2002-09-01
Project End
2006-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
4
Fiscal Year
2005
Total Cost
$339,750
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Pediatrics
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Yu, Xiaocong; Tsibane, Tshidi; McGraw, Patricia A et al. (2008) Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Nature 455:532-6
Yu, Xiaocong; McGraw, Patricia A; House, Frances S et al. (2008) An optimized electrofusion-based protocol for generating virus-specific human monoclonal antibodies. J Immunol Methods 336:142-51