Anti-cocaine vaccine development

Abstract

Cocaine abuse is an ongoing and serious problem which has lead to the growth of a brutal criminal enterprise, particularly in the Americas and Europe. At present, there are no effective pharmacological agents available to treat the addiction by blocking cocaine or reversing its effects. In order to help motivated addicts conquer their addiction, vaccines against cocaine are being developed, and one has progressed to clinical trials. This review will discuss the concept of anti-drug vaccines in general, the successes and limitations of the various anti-cocaine vaccine approaches, the results of the clinical trials with an anti-cocaine vaccine, and some new vaccine-mediated approaches to combat cocaine addiction. KeywordsSubstance Abuse; Vaccination; Cocaine; Immunotherapy HistoryCocaine is one of the oldest known drugs. The leaves of the coca plant have been chewed by the indigenous peoples of South America for thousands of years to increase stamina for high altitude work and to afford feelings of well-being. In 1859, the active ingredient in coca was isolated and named cocaine, and it was considered a rather benign drug until the beginning of the 20 th century, when the negative aspects of its use became widely recognized (1). The sale and distribution of opium, coca leaves, and their derivatives was restricted in the United States under the 1914 Harrison Narcotics Tax Act to the practice of medicine, dentistry, and veterinary medicine. However, the law was not strictly enforced for cocaine, and there was open use of the drug for a number of years, although this was generally limited to the minority and low income urban populations, artists, and musicians (2). The addictive properties of cocaine were again gradually recognized, but in spite of this and increased efforts to enforce drug laws, the use of cocaine, particularly the smoked free base form known as crack, exploded during the 1970's and 80's. There is some light on the horizon, however, as data gathered by SAMSHA, the Substance Abuse and Mental Health Services Administration of the US Department of Health and Human Services shows that admissions to substance abuse treatment for cocaine decreased from 1995 to 2005, and the age of those admitted went up substantially (3). Even though there was a decrease in admissions among African-Americans, there was an increase Anti-drug VaccinesIt has been known and studied for at least 50 years that small molecules (haptens) will not usually elicit an immune response unless they are covalently attached to an immunogenic protein (6,7). This results in the body's tolerance for most medications and chemical exposures without significant harmful immune reactions. Allergic reactions to medicines like penicillin occur when the immune system recognizes the chemical or its metabolic products after they have been bound to native proteins, allowing for antigen presentation and initiation of the immune response (8). Therefore, to produce an anti-drug vaccine, the hapten is covalently attached to a foreign carrier prote...

Hapten-specific naïve B cells are biomarkers of vaccine efficacy against drugs of abuse

“…Despite promising animal studies, vaccines against drugs of abuse have not yet met clinical expectations because few subjects achieved effective serum antibody titers [8-14]. Evaluation of vaccines against nicotine or cocaine showed that only ~30% of immunized subjects developed clinically effective drug-specific serum IgG antibodies concentrations of at least 40 μg/ml necessary to achieve smoking cessation or abstinence from cocaine [10,11].…”

Subunit Stabilization and Polyethylene Glycolation of Cocaine Esterase Improves In Vivo Residence Time

“…The antibody titers were sufficient to block reinstatement induced by a single dose of drug, but this protective effect was overcome with either repeated cocaine dosing or by increasing the dose (Carrera et al, 2000(Carrera et al, , 2001. The most effective vaccines to date have been against bovine serum albumin-or cholera toxin B-conjugated norcocaine (Fox et al, 1996;Kantak et al, 2000), and their success in eliciting good antibody titers has resulted in the initiation of clinical trials in humans (Kosten et al, 2002;Kinsey et al, 2010). A variant of passive immunization using catalytic monoclonal antibodies, which can not only sequester but also hydrolyze cocaine, was unfortunately not therapeutically active for more than 72 h after administration (Landry et al, 1993;Yang et al, 1996;Matsushita et al, 2001).…”

Nuevas vacunas contra la morfina-heroína

“…Estas nuevas estrategias experimentales están basadas en el diseño y síntesis de diversas formulaciones estructurales de vacunas terapéuticas contra la adicción a cocaína, [10][11][12][13] nicotina [14][15][16] y heroína/morfina, 17-20 las cuales, al ser dosificadas en esquemas de inmunización activa en modelos animales como el roedor o en el humano, inducen la producción de anticuerpos séricos específicos que reconocen y se unen a estas sustancias en el espacio intravascular sistémico. Estos anticuerpos anti-droga poseen la capacidad de secuestrar al compuesto adictivo circulante en el torrente sanguíneo ya que los anticuerpos son macromoléculas (≈150 kD) que normalmente no permean la barrera hematoencefálica, formando así complejos moleculares anticuerpo-droga de alto peso molecular, que "secuestran" e impiden el paso de la droga a través de la barrera hematoencefálica.…”