Rabies virus is a NIAID Category C agent. There is no known treatment for rabies after clinical symptoms appears; however, the disease can be prevented even after exposure to the virus by post-exposure prophylaxis that includes passive immunization with anti-rabies immunoglobulin (RIG). Currently, RIG for PEP is prepared from the sera of rabies virus-immune humans (HRIG) or horses (ERIG). Due to the safety and availability concerns the development of a human anti-rabies monoclonal antibody (hu-ar-Mab) cocktail product is proposed for rabies PEP for potential biowarfare applications. Hu-ar-Mabs have been produced that neutralize a broad spectrum of rabies virus strains and protect hamsters against a lethal rabies virus infection when administered after infection. Three hu-ar-Mabs have been selected from a panel of Mab candidates for their high virus neutralization titers and ability to neutralize a broad spectrum of rabies virus strains. It is proposed to produce sufficient quantities of these three hu-ar-Mabs using a rhabdovirus expression vector to allow for further biological and physiochemical characterization of the Mabs in order to create an optimal Mab cocktail product for rabies PEP treatment. After individually testing the three hu-ar-Mabs in mouse and hamster infectivity models, a cocktail will be formulated and tested in a non-human primate (squirrel monkey) infectivity model to justify safety testing of the product in a human clinical trial.
