1

UI  - 8

AU  - Bagasra O

AU  - Forman LJ

AU  - Howeedy A

AU  - Whittle P

AD  - Jefferson Medical College, Division of Infectious Diseases, Philadelphia, PA 19107

TI  - A potential vaccine for cocaine abuse prophylaxis

AB  - Presently, there are estimated to be 1.5 to 2.0 million individuals infected with HIV-1 in the U.S. and about 12 million worldwide. In the U.S. over 90% of reported cases of AIDS occurred among two subgroups, homosexual males and intravenous substance abusers (IVSAs). Currently, there is no anti-cocaine addiction medication available. In order to explore vaccination as an alternative means for protection against cocaine addition, we immunized inbred male Fisher rats with either cocaine emulsification in complete Freund adjuvant (CFA) or with cocaine conjugated with keyhole limpet hemocyanin (KLH), as carrier plus CFA. Animals were initially immunized with 0.1 mg/animal of cocaine or cocaine-KLH. Animals were given a booster with the corresponding agents after 4 weeks. Ten animals/group were used. Controls received normal saline at the time of immunizations. These animals were injected, intraperitoneally, with 25 mg/kg of cocaine, and were examined for the analgesic effect of cocaine by the hot plate method. The average analgesic effect of cocaine was significantly reduced (p greater than 0.03) in animals immunized with cocaine-KLH (13.77 s) as compared to saline controls (21.6 s). Fifty percent of the animals (5/10) in the cocaine-KLH group and 33% of the animals (3/9) in the cocaine immunized group appeared completely resistant to the effect of cocaine on the central nervous system (CNS). We also have determined the levels of cocaine-specific antibodies produced by each animal by an ELISA method. Degree of protection from cocaine seems to correlate well with the amount of anti-cocaine antibodies produced by each animal (- 0.61).(ABSTRACT TRUNCATED AT 250 WORDS)

MH  - analysis

MH  - Animal

MH  - Antibodies

MH  - Antibody Formation

MH  - Antigen-Antibody Complex

MH  - Cocaine

MH  - Comparative Study

MH  - Complement 3c

MH  - Enzyme-Linked Immunosorbent Assay

MH  - Freund's Adjuvant

MH  - Hemocyanin

MH  - immunology

MH  - Kidney

MH  - Male

MH  - prevention & control

MH  - Random Allocation

MH  - Rats

MH  - Rats,Inbred F344

MH  - Substance-Related Disorders

MH  - Support,U.S.Gov't,P.H.S.

MH  - Vaccination

MH  - Vaccines

RP  - NOT IN FILE

NT  - UI - 92363733LA - engRN - 0 (Antigen-Antibody Complex)RN - 0 (Vaccines)RN - 0 (keyhole-limpet hemocyanin)RN - 50-36-2 (Cocaine)RN - 80295-44-9 (Complement 3c)RN - 9007-81-2 (Freund's Adjuvant)RN - 9013-72-3 (Hemocyanin)PT - Journal ArticleID - AA-07858/AA/NIAAADA - 19920911IS - 0162-3109SB - IMCY - NETHERLANDSJC - GY3

UR  - PM:1500284

SO  - Immunopharmacology 1992 May ;23(3):173-179

 

2

UI  - 5

AU  - Fox BS

AU  - Kantak KM

AU  - Edwards MA

AU  - Black KM

AU  - Bollinger BK

AU  - Botka AJ

AU  - French TL

AU  - Thompson TL

AU  - Schad VC

AU  - Greenstein JL

AU  - Gefter ML

AU  - Exley MA

AU  - Swain PA

AU  - Briner TJ

AD  - ImmuLogic Pharmaceutical Corporation, Waltham, Massachusetts 02154, USA

TI  - Efficacy of a therapeutic cocaine vaccine in rodent models

AB  - Cocaine abuse is a major medical and public health concern in the United States, with approximately 2.1 million people dependent on cocaine. Pharmacological approaches to the treatment of cocaine addiction have thus far been disappointing, and new therapies are urgently needed. This paper describes an immunological approach to cocaine addiction. Antibody therapy for neutralization of abused drugs has been described previously, including a recent paper demonstrating the induction of anti-cocaine antibodies. However, both the rapidity of entry of cocaine into the brain and the high doses of cocaine frequently encountered have created challenges for an antibody-based therapy. Here we demonstrate that antibodies are efficacious in an animal model of addiction. Intravenous cocaine self-administration in rats was inhibited by passive transfer of an anti-cocaine monoclonal antibody. To actively induce anti-cocaine antibodies, a cocaine vaccine was developed that generated a high-titer, long-lasting antibody response in mice. Immunized mice displayed a significant change in cocaine pharmacokinetics, with decreased levels of cocaine measured in the brain of immunized mice only 30 seconds after intravenous (i.v.) administration of cocaine. These data establish the feasibility of a therapeutic cocaine vaccine for the treatment of cocaine addiction

MH  - administration & dosage

MH  - Animal

MH  - Antibodies

MH  - Brain

MH  - Cocaine

MH  - Conditioning,Operant

MH  - Evaluation Studies

MH  - Haptens

MH  - immunology

MH  - Immunotherapy,Active

MH  - Injections,Intravenous

MH  - Male

MH  - Mice

MH  - Mice,Inbred BALB C

MH  - Opioid-Related Disorders

MH  - pharmacokinetics

MH  - Rats

MH  - Rats,Wistar

MH  - Self Administration

MH  - Serum Albumin,Bovine

MH  - Support,U.S.Gov't,P.H.S.

MH  - therapy

MH  - Vaccines

RP  - NOT IN FILE

NT  - UI - 96434688LA - engRN - 0 (Haptens)RN - 0 (Serum Albumin, Bovine)RN - 0 (Vaccines)RN - 50-36-2 (Cocaine)PT - Journal ArticleDA - 19961104IS - 1078-8956SB - IMCY - UNITED STATESJC - CG5

UR  - PM:8837612

SO  - Nat Med 1996 Oct ;2(10):1129-1132

 

3

UI  - 4

AU  - Fox BS

AD  - ImmuLogic Pharmaceutical Corporation, Waltham, MA 02154, USA. FoxB@ImmuLogic.com

TI  - Development of a therapeutic vaccine for the treatment of cocaine addiction

AB  - No pharmacotherapies have yet been approved for the treatment of cocaine addiction. One new approach is to block the effects of cocaine with anti-cocaine antibodies induced by a therapeutic cocaine vaccine. A cocaine vaccine has been developed which induces a cocaine-specific antibody response in rodents. The antibody binds to cocaine in the circulation and can be shown to inhibit the ability of cocaine to enter the brain. Furthermore, anti-cocaine antibody can inhibit cocaine self- administration in rats. These data suggest that a cocaine vaccine may be a powerful therapeutic tool. The intent is to immunized motivated patients with the vaccine as part of a comprehensive treatment program. If the patient uses cocaine after being vaccinated, the antibody will inhibit the reinforcing activity of cocaine and decrease the likelihood of relapse

MH  - administration & dosage

MH  - Animal

MH  - Antibodies

MH  - Antigen-Antibody Complex

MH  - Behavior,Addictive

MH  - blood

MH  - Blood-Brain Barrier

MH  - Brain

MH  - Brain Chemistry

MH  - Carrier Proteins

MH  - Cocaine

MH  - Cocaine-Related Disorders

MH  - Disease Models,Animal

MH  - drug therapy

MH  - Human

MH  - Immunization,Passive

MH  - immunology

MH  - Mice

MH  - pharmacokinetics

MH  - pharmacology

MH  - Rats

MH  - Self Administration

MH  - Self Medication

MH  - Serum Albumin,Bovine

MH  - Support,U.S.Gov't,P.H.S.

MH  - Vaccines

RP  - NOT IN FILE

NT  - UI - 98110501LA - engRN - 0 (Antigen-Antibody Complex)RN - 0 (Carrier Proteins)RN - 0 (Serum Albumin, Bovine)RN - 0 (Vaccines)RN - 50-36-2 (Cocaine)PT - Journal ArticleDA - 19980504IS - 0376-8716SB - IMCY - IRELANDJC - EBS

UR  - PM:9449013

SO  - Drug Alcohol Depend 1997 Dec 15 ;48(3):153-158

 

4

UI  - 7

AU  - Gallacher G

TI  - A potential vaccine for cocaine abuse prophylaxis?

AB  - O. Bagasra, L.J. Forman, A. Howeedy, and P.A. Whittle recently conveyed the preparation of a cocaine immunogen that is a potential vaccine for cocaine abuse prophylaxis (Immunopharmacology: 1992, 23, 173-179). These investigators claim to have prepared a cocaine immunogen via reaction of cocaine with sodium metaperiodate followed by carrier protein, and to have generated anti-cocaine antibodies by using this immunogen. Periodate is used to conjugate haptens that contain a vicinal diol (or similar) group to carrier proteins and would not be expected to couple cocaine to protein. The authors of the above publication reported titres for antibodies generated by using their immunogen, but did not describe competitive inhibition of antibody binding by cocaine and did not report the specificity characteristics of their antibodies. The present author is not convinced by the claims made by Bagasra et al

MH  - Antibodies

MH  - Antibody Formation

MH  - Carrier Proteins

MH  - chemistry

MH  - Cocaine

MH  - Haptens

MH  - Human

MH  - immunology

MH  - Vaccines

RP  - NOT IN FILE

NT  - UI - 94266609LA - engRN - 0 (Vaccines)RN - 50-36-2 (Cocaine)PT - CommentPT - LetterDA - 19940712IS - 0162-3109SB - IMCY - NETHERLANDSJC - GY3

UR  - PM:8206756

SO  - Immunopharmacology 1994 Jan ;27(1):79-84

 

5

UI  - 1

AU  - Kantak KM

AU  - Collins SL

AU  - Lipman EG

AU  - Bond J

AU  - Giovanoni K

AU  - Fox BS

AD  - Department of Psychology, Boston University, Massachusetts 02215, USA. kkantak@bu.edu

TI  - Evaluation of anti-cocaine antibodies and a cocaine vaccine in a rat self-administration model

AB  - RATIONALE: Previous pre-clinical studies with an anti-cocaine monoclonal antibody left open several issues critical to assessing the effectiveness of a vaccine for altering cocaine self-administration behavior. OBJECTIVES: The objectives of this study were to determine, first, whether changes in self-administration behavior would be systematically related to antibody level and, second, how the antibody affected the self-administration of different doses of cocaine. METHODS: Two experiments were conducted using a second-order schedule of drug delivery in rats. The first was a passive-administration study using the anti-cocaine monoclonal antibody MO240 to examine the relationship between antibody level and cocaine self-administration behavior, and the second was an active-immunization study to examine the efficacy of the cocaine vaccine IPC-1010 for blocking various doses of self-administered cocaine. RESULTS: The passive-administration experiment with control and 4-mg or 12-mg MO240 treatments showed that antagonism of the 1 mg/kg cocaine training dose was dependent on antibody level. In animals whose serum antibody levels were sustained above 0.05 mg/ml, there was a sufficient amount of antibody to reduce drug-seeking behavior and drug intake. In the active-immunization experiment, the cocaine vaccine IPC-1010 induced average serum antibody levels of 0.08 mg/ml and reduced the reacquisition of behavior by 1 mg/kg cocaine. Antagonism of cocaine self-administration after immunization was evident across a range of doses of cocaine and was only apparent in animals whose serum antibody levels exceeded 0.05 mg/ml. Furthermore, there was no evidence that the antagonism was surmountable within the dose range examined (up to 5.6 mg/kg). CONCLUSIONS: Antagonism of cocaine self-administration across a range of doses is feasible after immunization with a cocaine vaccine as long as antibody levels are of a sufficient concentration

MH  - administration & dosage

MH  - Animal

MH  - Antibodies

MH  - Antibodies,Monoclonal

MH  - blood

MH  - Brain

MH  - Cocaine

MH  - Dose-Response Relationship,Drug

MH  - Extinction (Psychology)

MH  - Immunization,Passive

MH  - immunology

MH  - Male

MH  - metabolism

MH  - Myocardium

MH  - pharmacokinetics

MH  - Rats

MH  - Rats,Wistar

MH  - Reinforcement (Psychology)

MH  - Self Administration

MH  - Support,U.S.Gov't,P.H.S.

MH  - Vaccination

MH  - Vaccines

RP  - NOT IN FILE

NT  - UI - 20216542LA - engRN - 0 (Antibodies)RN - 0 (Antibodies, Monoclonal)RN - 0 (Vaccines)RN - 50-36-2 (Cocaine)PT - Journal ArticleID - DA 08979/DA/NIDADA - 20000427IS - 0033-3158SB - IMCY - GERMANYJC - QGI

UR  - PM:10755738

SO  - Psychopharmacology (Berl) 2000 Feb ;148(3):251-262

 

6

UI  - 3

AU  - Lutwick LI

AD  - Department of Medicine, VA Medical Center, Brooklyn, New York, USA

TI  - Unconventional vaccine targets. Immunization for pregnancy, peptic ulcer, gastric cancer, cocaine abuse, and atherosclerosis

AB  - Vaccine technology can be applied to targets of intervention that currently have not been considered preventable by immunization. Targets include some diseases caused by, or related to, infectious agents, and other conditions clearly unassociated with disease pathogens. This article considers vaccines for pregnancy, peptic ulcer disease, gastric cancer, cocaine abuse and atherosclerosis

MH  - Animal

MH  - Arteriosclerosis

MH  - Cocaine

MH  - Cocaine-Related Disorders

MH  - Contraception,Immunologic

MH  - Female

MH  - immunology

MH  - Peptic Ulcer

MH  - Pregnancy

MH  - prevention & control

MH  - Stomach Neoplasms

MH  - Vaccines

RP  - NOT IN FILE

NT  - UI - 99215015LA - engRN - 0 (Vaccines)PT - Journal ArticlePT - ReviewPT - Review, TutorialDA - 19990708IS - 0891-5520SB - IMCY - UNITED STATESJC - IDC

UR  - PM:10198802

SO  - Infect Dis Clin North Am 1999 Mar ;13(1):245-64, ix

 

7

UI  - 6

AU  - Nadis S

TI  - Drugs institute gives grant for cocaine vaccine

MH  - Animal

MH  - Cocaine

MH  - Drug Industry

MH  - economics

MH  - Financing,Government

MH  - Human

MH  - National Institutes of Health (U.S.)

MH  - Nicotine

MH  - prevention & control

MH  - Rats

MH  - Research Support

MH  - Substance-Related Disorders

MH  - United States

MH  - Vaccines

RP  - NOT IN FILE

NT  - UI - 96338208LA - engRN - 0 (Vaccines)RN - 50-36-2 (Cocaine)RN - 54-11-5 (Nicotine)PT - NewsDA - 19960918IS - 0028-0836SB - IMCY - ENGLANDJC - NSC

UR  - PM:8757117

SO  - Nature 1996 Aug 15 ;382(6592):568

 

8

UI  - 2

AU  - Schabacker DS

AU  - Kirschbaum KS

AU  - Segre M

AD  - Departments of Pathobiology and Chemistry, University of Illinois, Urbana, IL 61802, USA

TI  - Exploring the feasibility of an anti-idiotypic cocaine vaccine: analysis of the specificity of anticocaine antibodies (Ab1) capable of inducing Ab2beta anti-idiotypic antibodies

AB  - Conventional vaccination with the cocaine molecule conjugated to a protein carrier is a new approach in the treatment of addiction. Experimentally, this strategy has been shown to alter the pharmacokinetics as well as the psychostimulant effect of a cocaine challenge. The purpose of this study was to investigate whether a more stable and less controversial molecule, an anti-idiotypic antibody, which mimics the configuration of the cocaine molecule (Ab2beta), could be successfully used instead of cocaine. Two cocaine conjugates that presented different areas of the cocaine molecule to the immune system were used to produce monoclonal antibodies specific for cocaine (Ab1). Several anti-idiotypic antibodies were then produced. Four were identified as Ab2beta, or internal images of the antigen; when injected into BALB/c mice, they elicited an anticocaine response. The anticocaine response elicited by one of the four Ab2beta (K1-4c) was sufficient to significantly reduce the level of cocaine that targeted the brain following cocaine challenge, compared with the level of cocaine found in the brain of control animals immunized with irrelevant antibody. In conclusion, the possibility of an anti-idiotypic vaccine seems to be worth pursuing

MH  - Animal

MH  - Antibodies

MH  - Antibodies,Anti-Idiotypic

MH  - Antibodies,Monoclonal

MH  - Antibody Specificity

MH  - biosynthesis

MH  - Brain

MH  - Cocaine

MH  - Cocaine-Related Disorders

MH  - Feasibility Studies

MH  - immunology

MH  - Immunotherapy,Active

MH  - metabolism

MH  - methods

MH  - Mice

MH  - Mice,Inbred BALB C

MH  - pharmacokinetics

MH  - Spleen

MH  - Support,Non-U.S.Gov't

MH  - Support,U.S.Gov't,P.H.S.

MH  - therapy

MH  - Vaccination

RP  - NOT IN FILE

NT  - UI - 20270063LA - engRN - 0 (Antibodies, Anti-Idiotypic)RN - 0 (Antibodies, Monoclonal)RN - 50-36-2 (Cocaine)PT - Journal ArticleDA - 20000531IS - 0019-2805SB - IMCY - ENGLANDJC - GH7

UR  - PM:10809958

SO  - Immunology 2000 May ;100(1):48-56