Efficacy of a therapeutic cocaine vaccine in rodent models

Abstract

Cocaine abuse is a major medical and public health concern in the United States, with approximately 2.1 million people dependent on cocaine. Pharmacological approaches to the treatment of cocaine addiction have thus far been disappointing, and new therapies are urgently needed. This paper describes an immunological approach to cocaine addiction. Antibody therapy for neutralization of abused drugs has been described previously, including a recent paper demonstrating the induction of anti-cocaine antibodies. However, both the rapidity of entry of cocaine into the brain and the high doses of cocaine frequently encountered have created challenges for an antibody-based therapy. Here we demonstrate that antibodies are efficacious in an animal model of addiction. Intravenous cocaine self-administration in rats was inhibited by passive transfer of an anti-cocaine monoclonal antibody. To actively induce anti-cocaine antibodies, a cocaine vaccine was developed that generated a high-titer, long-lasting antibody response in mice. Immunized mice displayed a significant change in cocaine pharmacokinetics, with decreased levels of cocaine measured in the brain of immunized mice only 30 seconds after intravenous (i.v.) administration of cocaine. These data establish the feasibility of a therapeutic cocaine vaccine for the treatment of cocaine addiction.

Novel Cocaine Vaccine Linked to a Disrupted Adenovirus Gene Transfer Vector Blocks Cocaine Psychostimulant and Reinforcing Effects

“…Monoclonal antibodies against cocaine decreased cocaine self-administration and its toxic effects in rats (Carrera et al, 2000;Kantak et al, 2000;Mets et al, 1998). However, passively administered antibodies have a rather short half-life compared with active immunization that generates immunological memory (Fox et al, 1996;Kantak et al, 2000).…”

“…In addition, a KLHconjugated vaccine against cocaine prevented the reinstatement of responding for cocaine in rats, a rodent model of relapse to cocaine use (Carrera et al, 2000). Immunization with a cocaine-bovine serum albumin (BSA) conjugate also produced specific antibodies against cocaine and increased the distribution of cocaine in plasma relative to the brain in mice (Fox et al, 1996). Immunization with succinylnorcocaine attached to cholera B toxin (IPC-1010 or TA-CD) decreased responding for cocaine and cocaine intake in rats, with serum antibody concentrations 40.05-0.07 mg/ml (Kantak et al, 2000(Kantak et al, , 2001, and this vaccine was well tolerated and produced specific antibodies in a dosedependent manner in a Phase I clinical trial (Kosten et al, 2002).…”

Avances en el desarrollo de productos biológicos para el tratamiento de la adicción a las drogas y las sobredosis

“…Several groups of investigators are working in developing anti-cocaine vaccines (Fox et al, 1996;Hicks et al, 2011;Kantak, 2003;Kosten et al, 2002;Martell, Mitchell, Poling, Gonsai, & Kosten, 2005), monoclonal antibodies, and enzymes to treat cocaine addiction or overdose. One of the vaccines, the TA-CD vaccine, has been evaluated in clinical trials.…”

The cocaine abusing parturient: a review of anesthetic considerations

“…Binding of antibodies included in the vaccine to cocaine in plasma may prevent entry of the drug into the central nervous system. 90,91 Despite promising initial results further investigations on the efficacy of cocaine vaccines in cocaine addiction are necessary. 8 8. .…”