Human monoclonal antibodies isolated from spontaneous Epstein-Barr virus-transformed tumors of Hu-SPL-SCID mice and specific for fusion protein display broad neutralizing activity toward respiratory syncytial virus

Abstract

Two human monoclonal antibodies, RF-1 and RF-2, specifically recognize the fusion protein of the human respiratory syncytial virus (RSV). These were isolated from spontaneous tumors in SCID mice reconstituted with human splenocytes and boosted with fusion protein. The tumors consisted of Epstein-Barr virus-transformed human B cells in animals with antigen-specific antibody titers>105. The binding affinity of RF-1 and RF-2 to the fusion protein is 1010 and 109 M-1, respectively. The antibodies bind specifically to a conformational epitope of the fusion protein on RSV-infected HEp-2 cells. Both antibodies display virus-neutralizing properties in vitro at concentrations varying between 8 and 1000 ng/mL. Virus neutralization applies to a broad variety of wild and laboratory-adapted virus strains belonging to both virus types A and B. These antibodies are potential candidates for passive immunotherapy of severe RSV infections.