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