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Cocaine vaccine dAd5GNE protects against moderate daily and high-dose “binge” cocaine use

The cocaine vaccine dAd5GNE is comprised of a disrupted serotype 5 adenovirus gene therapy vector covalently conjugated to the cocaine analog GNE. The vaccine evokes a high titer of circulating anti-cocaine antibodies that prevent cocaine from reaching its cognate receptors in the central nervous sy...

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Autores principales: Havlicek, David F., Rosenberg, Jonathan B., De, Bishnu P., Hicks, Martin J., Sondhi, Dolan, Kaminsky, Stephen M., Crystal, Ronald G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703925/
https://www.ncbi.nlm.nih.gov/pubmed/33253224
http://dx.doi.org/10.1371/journal.pone.0239780
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author Havlicek, David F.
Rosenberg, Jonathan B.
De, Bishnu P.
Hicks, Martin J.
Sondhi, Dolan
Kaminsky, Stephen M.
Crystal, Ronald G.
author_facet Havlicek, David F.
Rosenberg, Jonathan B.
De, Bishnu P.
Hicks, Martin J.
Sondhi, Dolan
Kaminsky, Stephen M.
Crystal, Ronald G.
author_sort Havlicek, David F.
collection PubMed
description The cocaine vaccine dAd5GNE is comprised of a disrupted serotype 5 adenovirus gene therapy vector covalently conjugated to the cocaine analog GNE. The vaccine evokes a high titer of circulating anti-cocaine antibodies that prevent cocaine from reaching its cognate receptors in the central nervous system. Prior studies have demonstrated the efficacy of dAd5GNE in models of occasional, moderate cocaine use. However, previous studies have not sufficiently evaluated the efficacy of dAd5GNE in models of the repetitive and high-dose “binge” use patterns common in human addicts. In the present study, we evaluated the capacity of dAd5GNE vaccination to protect against “binge” cocaine use and circumstances where vaccinated addicts attempt to override the vaccine. We modeled repetitive daily cocaine use in vaccinated Balb/c mice and African green monkeys, and evaluated high-dose “binge” scenarios in Balb/c mice. In each model of daily use the dAd5GNE vaccine prevented cocaine from reaching the central nervous system. In the high-dose “binge” model, vaccination decreased cocaine-induced hyperactivity and reduced the number of cocaine-induced seizures. Based on this data and our prior data in rodents and nonhuman primates, we have initiated a clinical trial evaluating the dAd5GNE anti-cocaine vaccine as a potential therapy for cocaine addicts who wish to stop cocaine use. If dAd5GNE vaccination is safe and produces high anti-cocaine antibody titers in the clinic, we hypothesize that the vaccine will restrict the access of cocaine to the central nervous system and inhibit cocaine-induced “highs” even in the context of moderate daily and high-dose “binge” use that might otherwise cause a drug-induced overdose.
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spelling pubmed-77039252020-12-03 Cocaine vaccine dAd5GNE protects against moderate daily and high-dose “binge” cocaine use Havlicek, David F. Rosenberg, Jonathan B. De, Bishnu P. Hicks, Martin J. Sondhi, Dolan Kaminsky, Stephen M. Crystal, Ronald G. PLoS One Research Article The cocaine vaccine dAd5GNE is comprised of a disrupted serotype 5 adenovirus gene therapy vector covalently conjugated to the cocaine analog GNE. The vaccine evokes a high titer of circulating anti-cocaine antibodies that prevent cocaine from reaching its cognate receptors in the central nervous system. Prior studies have demonstrated the efficacy of dAd5GNE in models of occasional, moderate cocaine use. However, previous studies have not sufficiently evaluated the efficacy of dAd5GNE in models of the repetitive and high-dose “binge” use patterns common in human addicts. In the present study, we evaluated the capacity of dAd5GNE vaccination to protect against “binge” cocaine use and circumstances where vaccinated addicts attempt to override the vaccine. We modeled repetitive daily cocaine use in vaccinated Balb/c mice and African green monkeys, and evaluated high-dose “binge” scenarios in Balb/c mice. In each model of daily use the dAd5GNE vaccine prevented cocaine from reaching the central nervous system. In the high-dose “binge” model, vaccination decreased cocaine-induced hyperactivity and reduced the number of cocaine-induced seizures. Based on this data and our prior data in rodents and nonhuman primates, we have initiated a clinical trial evaluating the dAd5GNE anti-cocaine vaccine as a potential therapy for cocaine addicts who wish to stop cocaine use. If dAd5GNE vaccination is safe and produces high anti-cocaine antibody titers in the clinic, we hypothesize that the vaccine will restrict the access of cocaine to the central nervous system and inhibit cocaine-induced “highs” even in the context of moderate daily and high-dose “binge” use that might otherwise cause a drug-induced overdose. Public Library of Science 2020-11-30 /pmc/articles/PMC7703925/ /pubmed/33253224 http://dx.doi.org/10.1371/journal.pone.0239780 Text en © 2020 Havlicek et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Havlicek, David F.
Rosenberg, Jonathan B.
De, Bishnu P.
Hicks, Martin J.
Sondhi, Dolan
Kaminsky, Stephen M.
Crystal, Ronald G.
Cocaine vaccine dAd5GNE protects against moderate daily and high-dose “binge” cocaine use
title Cocaine vaccine dAd5GNE protects against moderate daily and high-dose “binge” cocaine use
title_full Cocaine vaccine dAd5GNE protects against moderate daily and high-dose “binge” cocaine use
title_fullStr Cocaine vaccine dAd5GNE protects against moderate daily and high-dose “binge” cocaine use
title_full_unstemmed Cocaine vaccine dAd5GNE protects against moderate daily and high-dose “binge” cocaine use
title_short Cocaine vaccine dAd5GNE protects against moderate daily and high-dose “binge” cocaine use
title_sort cocaine vaccine dad5gne protects against moderate daily and high-dose “binge” cocaine use
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703925/
https://www.ncbi.nlm.nih.gov/pubmed/33253224
http://dx.doi.org/10.1371/journal.pone.0239780
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