Human therapeutic cocaine vaccine: safety and immunogenicity

Kosten, Thomas R.; Rosen, Marc I.; Bond, Julian F.; Settles, Michael; Roberts, J St Clair; Shields, John G.; Jack, L C; Fox, Barbara S.

doi:10.1016/s0264-410x(01)00425-x

Cited by 179 publications

(150 citation statements)

References 9 publications

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“…Increased body temperature was observed in one out of the eight patients in each of the active treatment groups, but not in the placebotreated group. This side-effect profile is markedly less than that reported for a cocaine-cholera-toxin conjugate vaccine, where 50% of subjects showed an increased temperature [10].…”

Section: Safety and Tolerability In Healthy Volunteerscontrasting

confidence: 62%

“…A 100% responder rate was also observed by us in another phase I study with a peptide derived from house dust mite allergen derp1 coupled to Qb (Kündig et al, unpublished). The only other peer-reviewed publication of a vaccination study in humans with a hapten is a cocaine-vaccination study [10]. In this study a cocaine derivative coupled to a carrier protein derived from the cholera toxin B was administered three times in the presence of Alum.…”

Section: Discussionmentioning

confidence: 99%

“…Both active immunization with morphine-BSA conjugates and passive immunization with the resultant antibodies reduced heroin selfadministration in rhesus monkeys [8,9]. Immunization has also proven effective against cocaine addiction in animal models and recently a cocaine vaccine was shown to be safe and immunogenic in humans [10].…”

Section: Introductionmentioning

confidence: 99%

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A therapeutic vaccine for nicotine dependence: preclinical efficacy, and phase I safety and immunogenicity

Maurer¹,

Jennings²,

Willers³

et al. 2005

Eur. J. Immunol.

258

198

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Nicotine is the principal addictive component in tobacco, and following uptake acts in the central nervous system. The smoking-cessation efforts of most smokers fail because a single slip often delivers sufficient nicotine to the brain to reinstate the drug-seeking behaviour. Blocking nicotine from entering the brain by induction of specific antibodies may be an effective means to prevent such relapses. The hapten nicotine was coupled to virus-like particles (VLP) formed by the coat protein of the bacteriophage Qb. In preclinical experiments, this Nicotine-Qb VLP (NicQb) vaccine induced strong antibody responses. After intravenous nicotine challenge, vaccinated mice exhibited strongly reduced nicotine levels in the brain compared with control mice. In a phase I study, 32 healthy non-smokers were immunized with NicQb. The vaccine was safe and welltolerated. All volunteers who received NicQb showed nicotine-specific IgM antibodies at day 7 and nicotine-specific IgG antibodies at day 14. Antibody levels could be boosted by a second injection or the addition of Alum as an adjuvant and the antibodies had a high affinity for nicotine. These data suggest that antibodies induced by NicQb may prevent relapses by sequestering nicotine in the blood of immunized smokers.

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Section: Safety and Tolerability In Healthy Volunteerscontrasting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A therapeutic vaccine for nicotine dependence: preclinical efficacy, and phase I safety and immunogenicity

Maurer¹,

Jennings²,

Willers³

et al. 2005

Eur. J. Immunol.

258

198

View full text Add to dashboard Cite

show abstract

“…Several vaccines against cocaine have been in development, with one tested in clinical trials (Carrera et al, 1995;Haney and Kosten, 2004;Kosten et al, 2002;Orson et al, 2009). For example, active immunization with a cocaine analog linked to keyhole limpet hemocyanin (KLH) significantly attenuated cocaine-induced psychomotor stimulation and sequestered cocaine in the periphery in rodents (Carrera et al, 1995(Carrera et al, , 2001.…”

Section: Introductionmentioning

confidence: 99%

Novel Cocaine Vaccine Linked to a Disrupted Adenovirus Gene Transfer Vector Blocks Cocaine Psychostimulant and Reinforcing Effects

Wee

Hicks

et al. 2011

Neuropsychopharmacol

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Immunotherapy is a promising treatment for drug addiction. However, insufficient immune responses to vaccines in most subjects pose a challenge. In this study, we tested the efficacy of a new cocaine vaccine (dAd5GNE) in antagonizing cocaine addiction-related behaviors in rats. This vaccine used a disrupted serotype 5 adenovirus (Ad) gene transfer vector coupled to a third-generation cocaine hapten, termed GNE (6-(2R,3S)-3-(benzoyloxy)-8-methyl-8-azabicyclo [3.2.1] octane-2-carboxamido-hexanoic acid). Three groups of rats were immunized with dAd5GNE. One group was injected with 3 H-cocaine, and radioactivity in the blood and brain was determined. A second group was tested for cocaine-induced locomotor sensitization. A third group was examined for cocaine self-administration, extinction, and reinstatement of responding for cocaine. Antibody titers were determined at various time-points. In each experiment, we added a control group that was immunized with dAd5 without a hapten. The vaccination with dAd5GNE produced long-lasting high titers (410 5 ) of anti-cocaine antibodies in all of the rats. The vaccination inhibited cocaine-induced hyperlocomotor activity and sensitization. Vaccinated rats acquired cocaine self-administration, but they showed less motivation to self-administer cocaine under a progressive-ratio schedule than control rats. When cocaine was not available in a session, control rats exhibited 'extinction burst' responding, whereas vaccinated rats did not. Moreover, when primed with cocaine, vaccinated rats did not reinstate responding, suggesting a blockade of cocaine-seeking behavior. These data strongly suggest that our dAd5GNE vector-based vaccine may be effective in treating cocaine abuse and addiction.

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“…The human therapeutic cocaine vaccine TA-CD has been tested in phase I clinical trial. This vaccine is well tolerated with dose related increases in antibody levels (33). On the other hand, the concentration of cocaine in acute overdose patients may exceed the serum antibody concentration.…”

Section: Pharmacokinetic-based Therapies For Cocaine Abusementioning

confidence: 99%

The Rhodococcus sp. Cocaine Esterase: A Bacterial Candidate for Novel Pharmacokinetic‐based Therapies for Cocaine Abuse

2003

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SummaryCocaine is a powerful central nervous stimulant and among the most abused of drugs. Despite decades of efforts, however, no effective pharmacological treatments are available against cocaine addiction or toxic effects. Classical receptor-antagonist therapeutic approaches have not yielded significant effects, although cocaine targets are well known, thus fostering development of alternative therapeutic strategies. Recent evidence indicates that a sensible approach for treatment of cocaine abuse could be to interfere with cocaine pharmacokinetics, i.e. by preventing the drug from reaching the receptors responsible for its biological effects. Administration of cocaine binding antibodies as well as catalytic antibodies and enzymes that hydrolyze cocaine represent potential alternative therapeutic approach(es). The discovery of the cocaine esterase from the strain MB1 of the bacterium Rhodococcus sp. (cocE) could be a major breakthrough in this field; cocE hydrolyzes cocaine faster than any known cocaine esterase and catalytic antibody. IUBMB Life, 55: 397-402, 2003 Keywords Rhodococcus sp. esterase; human plasma butyrylcholinesterase; human liver carboxylesterase-1; human liver carboxylesterase-2; cocaine binding antibodies; cocaine binding catalytic antibodies; cocaine metabolism.

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Human therapeutic cocaine vaccine: safety and immunogenicity

Cited by 179 publications

References 9 publications

A therapeutic vaccine for nicotine dependence: preclinical efficacy, and phase I safety and immunogenicity

A therapeutic vaccine for nicotine dependence: preclinical efficacy, and phase I safety and immunogenicity

Novel Cocaine Vaccine Linked to a Disrupted Adenovirus Gene Transfer Vector Blocks Cocaine Psychostimulant and Reinforcing Effects

The Rhodococcus sp. Cocaine Esterase: A Bacterial Candidate for Novel Pharmacokinetic‐based Therapies for Cocaine Abuse

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