Development of a cocktail of recombinant-expressed human rabies virus-neutralizing monoclonal antibodies for postexposure prophylaxis of rabies.
To provide a cost-effective and safe replacement for human rabies immunoglobulin (HRIG), we used DNA recombinant technology to express 3 human rabies virus-neutralizing human monoclonal antibodies (huMAbs) in a rhabdovirus vector (RhV). Infection of either baby hamster kidney cells or CHO cells, with the resulting RhV-huMAb recombinant viruses, yielded high-level production (< or =40 micro g/mL/48 h) of RhV recombinant-expressed huMAbs (rhuMAbs) that differ in both isotype and epitope-recognition specificity. A cocktail of these rhuMAbs neutralizes several fixed and street wild-type rabies viruses (RVs). Mice and hamsters treated only once with this rhuMAb cocktail after infection with a lethal dose of RV were protected. In the mouse models, the postexposure prophylaxis (PEP) efficacy obtained with the rhuMAb cocktail was comparable to that obtained with HRIG, a finding strongly suggesting that rhuMAbs should be given serious consideration for use in future PEP of humans.
Prosniak
Mikhail
M
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. b_dietzshold@mail.jci.tju.edu
Faber
Milosz
M
Hanlon
Cathleen A
CA
Rupprecht
Charles E
CE
Hooper
D Craig
DC
Dietzschold
Bernhard
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D015870:Gene Expression; D005818:Genetic Engineering; D006801:Humans; D007116:Immunization, Passive; D051379:Mice; D009500:Neutralization Tests; D011818:Rabies / Q000276:immunology* / Q000517:prevention & control*; D011820:Rabies virus / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D011994:Recombinant Proteins