Vaccines against stimulants: cocaine and MA

Abstract

While the worldwide prevalence of cocaine use remains significant, medications, or small molecule approaches, to treat drug addictions have met with limited success. Anti-addiction vaccines, on the other hand, have demonstrated great potential for treating drug abuse using a distinctly different mechanism of eliciting an antibody response that blocks the pharmacological effects of drugs. We provide a review of vaccine-based approaches to treating stimulant addictions; specifically and cocaine addictions. This selective review article focuses on the one cocaine vaccine that has been into clinical trials and presents new data related to pre-clinical development of a methamphetamine (MA) vaccine. We also review the mechanism of action for vaccine induced antibodies to abused drugs, which involves kinetic slowing of brain entry as well as simple blocking properties. We present pre-clinical innovations for MA vaccines including hapten design, linkage to carrier proteins and new adjuvants beyond alum. We provide some new information on hapten structures and linkers and variations in protein carriers. We consider a carrier, outer membrance polysaccharide coat protein (OMPC), that provides some self-adjuvant through lipopolysaccharide components and provide new results with a monophosopholipid adjuvant for the more standard carrier proteins with cocaine and MA. The review then covers the clinical trials with the cocaine vaccine TA-CD. The clinical prospects for advances in this field over the next few years include a multi-site cocaine vaccine clinical trial to be reported in 2013 and phase 1 clinical trials of a MA vaccine in 2014.

Keywords: clinical trial; cocaine; stimulants; vaccines.

Figure 1

Mechanism of action of a vaccine against cocaine addiction. In the absence of the vaccine, cocaine is readily absorbed at the blood–brain barrier and thereby enters the brain. As shown in the top part of this figure, the vaccine interacts with dendritic blood cells to produce antibodies from B-cells that are secreted into the blood stream. In the brain, the drug causes reinforcement of pleasurable effects, or the ‘high’ associated with cocaine. If a vaccine is administered, it stimulates the production of antibodies against cocaine. Subsequently, if cocaine is taken, the antibodies bind to the drug and sequester it in the blood circulation. This antibody–drug binding prevents the cocaine from rapidly leaving the blood vessels and entering the brain, thereby reducing the drug's euphoric effects

Figure 2

Chemical structures for MIQ-N-succinate synthesis