The objective of this project is to generate rabies virus neutralizing human monoclonal antibody (mAbs), preferentially of the high affinity IgG isotype, so that a """"""""cocktail"""""""" of several neutralizing human mAbs can be prepared against multiple antigenic sites on the viral glycoprotein (GP) and ribonucleoprotein (RNP) complex. Specifically, this project aims to: (l) generate at least 15 high-affinity, virus-neutralizing human mAbs against various antigenic determinants on rabies virus using human hybridoma technology and (2) show that these mAbs protect animals against lethal rabies challenge. B cells isolated from peripheral blood (10-14 days) after booster vaccine) will be immortalized by infection with EBV, and cells producing rabies virus-specific antibody, detected in culture supernatants by ELISA, will be fused to produce mouse-human hybrids. These hybrids will be cloned, and cells producing rabies virus-specific antibody expanded. Rabies virus-specific mAbs generated in this fashion will be fully characterized in vitro for isotype, specificity, affinity, and VNA titre and in vivo for post-exposure efficacy in mice and the Syrian hamster model.

Project Start
1995-07-10
Project End
1997-06-29
Budget Start
1995-07-10
Budget End
1996-07-09
Support Year
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107