Exploring the Feasibility of an Anti-Idiotypic Cocaine Vaccine
Schabacker, Daniel Steven
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Permalink
https://hdl.handle.net/2142/87139
Description
Title
Exploring the Feasibility of an Anti-Idiotypic Cocaine Vaccine
Author(s)
Schabacker, Daniel Steven
Issue Date
1998
Doctoral Committee Chair(s)
Mariangela Segre
Department of Study
Veterinary Clinical Medicine
Discipline
Veterinary Clinical Medicine
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Health Sciences, Public Health
Language
eng
Abstract
Cocaine addiction is a major public health problem for which there are no proven psychotherapies or pharmacotherapies. Upon entry into the body, cocaine rapidly partitions to the brain. A possible means of negating 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. In rodents, Carrera R. et al. and Fox B. S. et al ., showed that following acute injection of cocaine, the presence of cocaine-specific antibodies (Ab1) in the blood reduced the level of cocaine reaching the brain, suppressed locomotor activity and stereotype behavior, and inhibited intravenous self administration. Thus, vaccination against cocaine is a feasible approach to the problem of addiction that would avoid the side effects of pharmacotherapies. In order to circumvent the problems associated with the instability of the cocaine molecule, we propose the use of an antibody molecule that mimics the configuration of cocaine as the antigen. In numerous cases anti-idiotypic vaccines have been used successfully to provide protective immunity. Cocaine specific Ab1 antibodies were elicited using two cocaine conjugates presenting opposites sides of the molecule to the immune system. These conjugates used either BE p-amino-phenethyl ester or norcocaine linked to KLH. The Ab2 antibodies produced from these Ab1 were linked to KLH and along with the adjuvant Alhydrogel were used for the vaccination of male BALB/c mice. Mice were challenged with 5 mg/kg of cocaine ip and sacrificed at 10 minutes. Through HPLC analysis we found a significant decrease in the level of cocaine in the brain extracts of mice vaccinated with Ab2-KLH, in comparison with the level of cocaine in the brain extracts of control mice. Through these experiments we have established the feasibility of an anti-idiotypic cocaine vaccine. A more thorough examination of the metabolism of cocaine in vaccinated mice, as well as behavioral studies must be performed to determine if this vaccination could be a practical treatment for cocaine addiction.
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