Exploring the feasibility of an anti‐idiotypic cocaine vaccine: analysis of the specificity of anticocaine antibodies (Ab1) capable of inducing Ab2βanti‐idiotypic antibodies

Schabacker, Daniel S.; Kirschbaum, Karen S.; Segre, Mariangela

doi:10.1046/j.1365-2567.2000.00004.x

Cited by 23 publications

(17 citation statements)

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“…In their study anti-cocaine monoclonal antibodies (Ab1) were produced by active immunization of a cocaine-protein conjugate. These Ab1 monoclonal antibodies were subsequently linked to KLH and vaccination of this conjugate induced formation of Ab2β which presented anti-cocaine effects upon drug challenge in mice (Schabacker et al, 2000). Yet, behavioral and pharmacokinetic tests have not been conducted to date.…”

Section: Cocainementioning

confidence: 99%

Immunopharmacotherapy: Vaccination strategies as a treatment for drug abuse and dependence

Moreno

Janda

2009

Pharmacology Biochemistry and Behavior

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Despite intensive efforts for its eradication, addiction to both legal and illicit drugs continues to be a major worldwide medical and social problem. Drug addiction is defined as a disease state in which the body relies on a substance for normal functioning and develops physical dependence leading to compulsive and repetitive use despite negative consequences to the user’s health, mental state or social life. Psychoactive substances such as cocaine, nicotine, alcohol, and amphetamines are able to cross the blood-brain barrier once ingested and temporarily alter the chemical balance of the brain. Current medications used for the treatment of dependence are typically agonists or antagonists of the drugs of abuse. The complex interrelations of the neuronal circuits have made it difficult to accurately predict the actions of potential agonist/antagonist drugs and have led to undesirable side effects within the central nervous system. Nearly forty years ago, a handful of groups began to explore the possibility of utilizing an individual’s own immune machinery to counteract the effects of drug exposure in an approach later termed by our laboratory, immunopharmacotherapy. Immunopharmacotherapy aims to use highly specific antibodies to sequester the drug of interest while the latter is still in the bloodstream. Thus, creation of the antibody-drug complex will blunt crossing of the blood brain barrier (BBB) not only counteracting the positive reinforcing effects of the drug but also preventing any detrimental side effects on the CNS. In the present mini-review we aim to present a focused summary, including relevant challenges and future directions, of the current state of cocaine and nicotine vaccines as these two programs have been the most successful to date.

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Section: Cocainementioning

confidence: 99%

Immunopharmacotherapy: Vaccination strategies as a treatment for drug abuse and dependence

Moreno

Janda

2009

Pharmacology Biochemistry and Behavior

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“…После слияния клетки дважды отмывали культуральной средой и высевали в 96-луночные культуральные планшеты с суточными перитонеальными макрофагами (5 × 10 3 клеток на лунку) из расчета 5 × 10 4 клеток на лунку по миеломе. Селекцию гибридов проводили в среде RPMI-1640 с добавлением 10% фетальной бычьей сыворотки (Sigma, США), содержащей: 10 -4 М гипоксантина, 4 × 10 -7 М аминоптерина и 1,6 × 10 -5 М тимидина [11]. В таблице 1 представлена схема проведения иммуноферментного анализа (ИФА) для отбора клонов, продуцирующих mAb2.…”

Section: материалы и методыunclassified

Preparation and Properties of Murine Anti-Idiotypic Monoclonal Antibodies Recognizing Primary Rabbit Polyclonal Antibodies Against Morphine Derivatives

et al. 2019

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Anti-idiotypic antibodies (Ab2), according to the network theory of Jerne, are second-generation immunoglobulins that are produced against the idiotype of an antibody to a specific antigen. Despite the large number of works devoted to the study of the properties of these proteins, their role in the regulation of the immune system is not fully known. It may consist in maintaining or blocking a minimal immune response to the antigen. The study of Ab2 is of great practical and scientific importance. The special properties of Ab2, namely, the ability to partially reproduce the structure of the primary antigen and, upon immunization, induce the appearance of tertiary antibodies, which, like first-generation antibodies, can bind to the antigen, have found application in the development of Ab2-based vaccines, in particular, for the treatment of tumors. In view of the presence of a number of limitations on research related to psychoactive substances, the development of Ab2- based vaccines against drug addiction also seems promising. To example, anti-idiotypic antibodies obtained for this purpose possessing a cocaine-like structure are described in the literature. In this work, murine monoclonal anti-idiotypic antibodies (mAb2) mimicking the structure of various morphine derivatives were obtained. Rabbit polyclonal antibodies to the 6-hemisuccinyl derivative of morphine conjugated with bovine serum albumin isolated by affinity chromatography were used as primary antibodies for immunization. Four hybridoma clones were obtained as a result of the fusion of immunized mice lymphocytes with mouse Sp2/0 mouse myeloma cells by the Milstein-Köhler method. After growth in animals, mAb2 produced by hybridoma cells were affinity purified. We investigated the physicochemical and antigenic properties of the isolated antibodies. It was shown that the obtained mAb2 differ in immunological specificity, competing in different degree with morphine derivatives for binding to first-generation antibodies. We tested the possibility of using the obtained mAb2 as antigen analogues in the solid-phase enzyme-linked immunosorbent assay to determine the titer of primary antibodies against morphine in the blood serum of laboratory animals immunized with morphine derivatives. Based on the obtained anti-idiotypic antibodies, it is proposed to develop test systems to determine the serum opiate-specific antibodies in people after specific vaccination for therapeutic or prophylactic purposes to avoid the use of drugs as antigens immobilized on the solid phase in the analysis.

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“…Nevertheless, hot-plate and place preference conditioning assays as well as attenuation of the discriminative properties of cocaine (35) confirmed that anti-cocaine antibodies had been formed in vaccinated rats. In 2000, an interesting idea was reported on by Schabacker (36), whereby a monoclonal anti-cocaine antibody was used as an anti-idiotype vaccine whose configuration mimics that of cocaine, presenting an internal image of the cocaine molecule to the immune system. The vaccinated mice showed reduced levels of cocaine in the brain following a challenge as well as similar levels of anti-cocaine antibodies in the serum as compared with mice vaccinated with a cocaine-KLH conjugate vaccine.…”

Section: Anti-cocaine Vaccinesmentioning

confidence: 99%

Anti-cocaine vaccine development

Kinsey¹,

Kosten²,

Orson³

2010

Expert Review of Vaccines

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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...

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Exploring the feasibility of an anti‐idiotypic cocaine vaccine: analysis of the specificity of anticocaine antibodies (Ab1) capable of inducing Ab2βanti‐idiotypic antibodies

Cited by 23 publications

References 24 publications

Immunopharmacotherapy: Vaccination strategies as a treatment for drug abuse and dependence

Immunopharmacotherapy: Vaccination strategies as a treatment for drug abuse and dependence

Preparation and Properties of Murine Anti-Idiotypic Monoclonal Antibodies Recognizing Primary Rabbit Polyclonal Antibodies Against Morphine Derivatives

Anti-cocaine vaccine development

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