The development of monoclonal human rabies virus-neutralizing antibodies as a substitute for pooled human immune globulin in the prophylactic treatment of rabies virus exposure.
To provide a more defined and safer replacement for the human rabies immune globulin (HRIG) from pooled serum which is currently used for treatment of exposure to rabies virus we have developed a series of human rabies virus-specific monoclonal antibodies. Mouse-human heterohybrid myeloma cells producing rabies virus-specific human monoclonal antibodies were prepared using B cells obtained from volunteers recently-immunized with a commercial rabies virus vaccine (HDCV). Cell lines producing antibody which neutralized the Evelyn-Rokitnicki-Abelseth (ERA) rabies virus strain in vitro were cloned and the resulting monoclonal antibodies characterized for isotype, specificity against a variety of rabies virus isolates, and neutralization capacity. The ability of the monoclonal antibodies to neutralize a variety of rabies virus strains in vitro correlated with their binding specificity for these viruses in an enzyme-linked immunoadsorbant assay (ELISA). A number of these antibodies have proven suitable for the formulation of a prophylactic human monoclonal antibody-based reagent which would provide significant advantages to the HRIG in having defined, reproducible specificity, lessened possibility of contamination with viral pathogens, and consistent availability.
Champion
J M
JM
Center for Neurovirology, Department of Microbiology and Immunology, Thomas Jefferson University, Rm. 454 JAH, 1020 Locust St., Philadelphia, PA 19107-6799, USA.
Kean
R B
RB
Rupprecht
C E
CE
Notkins
A L
AL
Koprowski
H
H
Dietzschold
B
B
Hooper
D C
DC
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D009500:Neutralization Tests; D011818:Rabies / Q000628:therapy*; D011820:Rabies virus / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral