Current challenges for the creation of effective vaccines against drugs of abuse

Drug use and addiction has remained at unacceptably high levels despite efforts to minimize the number of users. The CDC estimates that in the USA approximately 21% of adults are current cigarette smokers, while 8.9% of the population 12 years and older are current users of illicit drugs, such as marijuana, cocaine, heroin, hallucinogens, inhalants and so on [1,2]. These statistics have remained constant despite welldocumented adverse medical consequences and government interventions aimed at prevention and treatment of substance abuse. It has been recognized that people continue their drug use owing to the sudden feelings of euphoria and pleasure they experience, which reinforces the behavior. Most users willing to undergo rehabilitation have few therapeutic options available and often must rely solely on behavioral therapy and counseling, which have high relapse rates (40–60%) among participants [3]. Some drugs, such as nicotine and opiates, have pharmacotherapies available that can improve the treatment outcome; yet, treating a drug with another drug inherently carries the risk of side effects. For example, a recent medication to treat nicotine addiction, Chantix (Pfizer, NY, USA), uses a nicotinic receptor partial agonist to both reduce cravings and minimize the pleasurable effects of tobacco products. Clinical studies demonstrate that it has the highest smoking cessation rates among all therapies tested [4]; yet, post-marketing surveillance has raised concerns over its safety. In 2008, the US FDA issued a warning that stated it was increasingly likely there is an association between Chantix and serious neuropsychiatric symptoms, such as suicidal thoughts and aggressive and erratic behavior. The severity of the health and social consequences associated with drug addiction and the shortcomings present in current therapies justify the continued development of novel or refined treatments. Immunopharmacotherapy is an approach that utilizes highly specific antibodies to sequester the drug in the periphery, thus blunting the amount that reaches the brain and thereby the pleasurable feelings that follow. As the therapeutic effect takes place in the periphery, side effects in the CNS are minimized. The use of immunotherapy has been investigated for the treatment of heroin, cocaine, phencyclidine, methamphetamine and nicotine addiction. Although several human clinical trials for cocaine and nicotine vaccines have been initiated, Phase II results have shown limited efficacy. A recurring obstacle has been the substantial variability of antibody levels elicited among individuals. NicVAX, a nicotine vaccine from Nabi Pharmaceuticals (MD, USA) and TA-CD, a cocaine vaccine from Celtic Pharma (Hamilton, Bermuda) are representative examples: in both studies, statistically significant quit rates compared with placebo were only observed in the subjects with the highest antibody concentrations. Once low and medium titer responders were taken into account, the overall quit rates fell to levels similar to the placebo group, further attesting to the fact that protective effects are directly proportional to the amount of circulating antibody elicited [5,6]. Therefore, alternate vaccine formulations with improved immunogenicity are needed before active Expert Rev. Vaccines 10(12), 1637–1639 (2011)