High level expression of a human rabies virus-neutralizing monoclonal antibody by a rhabdovirus-based vector.
Humans exposed to rabies virus must be promptly treated by passive immunization with anti-rabies antibody and active immunization with rabies vaccine. Currently, antibody prepared from pooled human serum or from immunized horses is utilized. However, neither of these reagents are readily available, entirely safe, or consistent in their biological activity. An ideal reagent would consist of a panel of human monoclonal antibodies. Such antibodies are now available, their only drawback being the cost of production. Using recombinant technology, we constructed a rabies virus-based vector which expresses high levels (approximately 60 pg/cell) of rabies virus-neutralizing human monoclonal antibody. The vector is a modified vaccine strain of rabies virus in which the rabies virus glycoprotein has been replaced with a chimeric vesicular stomatitis virus glycoprotein, and both heavy and light chain genes encoding a human monoclonal antibody have been inserted. This recombinant virus can infect a variety of mammalian cell lines and is non-cytolytic, allowing the use of cell culture technology routinely employed to produce rabies vaccines.
Morimoto
K
K
Department of Microbiology and Immunology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
Schnell
M J
MJ
Pulmanausahakul
R
R
McGettigan
J P
JP
Foley
H D
HD
Faber
M
M
Hooper
D C
DC
Dietzschold
B
B
D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000276:immunology; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000276:immunology; D000918:Antibody Specificity; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D009500:Neutralization Tests; D010957:Plasmids; D011820:Rabies virus / Q000235:genetics / Q000276:immunology*; D012209:Rhabdoviridae; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral