The overall objective of this collaborative research project is to develop novel methods for the treatment and postexposure prophylaxis of human rabies. There is currently no treatment for rabies, a disease causing tens of thousands of deaths annually, with a near 100% case-fatality rate. We have developed an anti-idiotypic rabies anti-receptor antibody (designated B9) that, in preliminary experiments, appears useful for treatment of established brain infection with rabies virus (by a mechanism of receptor blockade) and for immunoprophylaxis (by inducing the formation of rabies neutralizing antibody). Specific goals of this Phase I proposal are to: 1) further investigate the use of B9 anti-receptor antibody for therapy of rabies in a laboratory animal model (mouse) and define optimal dose and schedule of treatment; 2) investigate the ability of 39 antibody to induce protective neutralizing rabies antibody and compare this reagent with a licensed rabies vaccine; 3) determine the toxic effects of 39 antibody in mice; and 4) prepare and purify a large amount of 39 antibody and a master hybridoma cell bank for these and future studies. The toxicology and efficacy studies will provide detailed information on the usefulness of the B9 anti-id for treatment and prophylaxis of human rabies.