EFFICACY OF A THERAPEUTIC COCAINE VACCINE IN RODENT MODELS

Cocaine abuse is a major medical and public health concern in the Unit ed States, with approximately 2.1 million people dependent on cocaine( 1). Pharmacological approaches to the treatment of cocaine addiction h ave thus far been disappointing(2,3), and new therapies are urgently n eeded. This paper describes an immunological approach to cocaine addic tion. Antibody therapy for neutralization of abused drugs has been des cribed previously(4), including a recent paper demonstrating the induc tion of anti-cocaine antibodies(5). However, both the rapidity of entr y of cocaine into the brain(6) and the high doses of cocaine frequentl y encountered(7) have created challenges for an antibody-based therapy . Here we demonstrate that antibodies are efficacious in an animal mod el of addiction. Intravenous cocaine self-administration in rats was i nhibited by passive transfer of an anti-cocaine monoclonal antibody. T o actively induce anti-cocaine antibodies, a cocaine vaccine was devel oped that generated a high-titer, long-lasting antibody response in mi ce. Immunized mice displayed a significant change in cocaine pharmacok inetics, with decreased levels of cocaine measured in the brain of imm unized mice only 30 seconds after intravenous (i.v.) administration of cocaine. These data establish the feasibility of a therapeutic cocain e vaccine for the treatment of cocaine addiction.