Exploring the feasibility of an anti-cocaine vaccine: Preliminary study

Our goal is to establish the feasibility of using anti-idiotypic antibodies to immunize mice against cocaine. Upon entry into the body cocaine rapidly partitions to the brain, A possible means to negate the pharmacological activity of cocaine would be to interrupt the delivery of the drug to its receptor in the brain. Specific antibodies that bind cocaine in the blood stream may effectively prevent the drug from reaching the brain. Although the use of anti-idiotypic antibodies which mimic cocaine may eventually be the more desirable immunogen, as a first step we wanted to find whether active immunization against cocaine affects the distribution of the drug in the brain. Three cocaine-KLH conjugates were used as immunogens. Cocaine derivatives were made immunogenic by conjugation to the carrier protein KLH. The first conjugate made the use of benzoylecgonine (BE) which could be directly attached to the KLH carrier protein by a simple condensation reaction between the BE carboxyl group and lysine residues (NH2) on the KLH molecule using cyclohexylcarbodiimide as the dehydrating reagent. The second and third conjugates used either BE p-amino-phenethyl ester or 2β-carbomethoxy-3β-(4-aminophenyl) tropane, respectively, (both possessing an active aromatic amine) which required the use of a bifunctional linker (SPDP) to conjugate to the KLH protein. BALB/c mice were immunized with these conjugates in CFA. The anti-cocaine antibody response was monitored by ELISA. The level of cocaine in extracts of brain tissue was analyzed by RP-HPLC. We found a decrease in the level of cocaine in the brain extract of animals immunized with the coniucat.es. in comoarison with the cocaine concentration in the brains of the unimmunized animals.