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 prod ucing rabies virus-specific human monoclonal antibodies were prepared using B cells obtained from volunteers recently-immunized with a commercial rabi es virus vaccine (HDCV). Cell lines producing antibody which neutralized th e Evelyn-Rokitnicki-Abelseth (ERA) rabies virus strain in vitro were cloned and the resulting monoclonal antibodies characterized for isotype, specifi city against a variety of rabies virus isolates, and neutralization capacit y. The ability of the monoclonal antibodies to neutralize a variety of rabi es virus strains in vitro correlated with their binding specificity for the se viruses in an enzyme-linked immunoadsorbant assay (ELISA), A number of t hese antibodies have proven suitable for the formulation of a prophylactic human monoclonal antibody-based reagent which would provide significant adv antages to the HRIG in having defined, reproducible specificity, lessened p ossibility of contamination with viral pathogens, and consistent availabili ty. (C) 2000 Elsevier Science B.V. All rights reserved.