Abstract
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.
Highlights
In the United States, over one million people use cocaine regularly [1] and cocaine contributes to >500,000 emergency room visits per yr [2]
A vaccine that elicits high titers of anti-cocaine antibodies capable of binding to cocaine would prevent cocaine from passing across the blood-brain barrier, reducing the reinforcing effects of a perceived high and serving as a potential clinical therapeutic for individuals trying to overcome addiction [3,4,5,6]
In the current study we modeled low to moderate repeated daily intravenous cocaine use in mice and nonhuman primates and modeled high-dose intravenous “binge” use in mice
Summary
In the United States, over one million people use cocaine regularly [1] and cocaine contributes to >500,000 emergency room visits per yr [2]. Cocaine use is a serious public health concern and there are currently no FDA approved therapies to treat cocaine addiction. A vaccine that elicits high titers of anti-cocaine antibodies capable of binding to cocaine would prevent cocaine from passing across the blood-brain barrier, reducing the reinforcing effects of a perceived high and serving as a potential clinical therapeutic for individuals trying to overcome addiction [3,4,5,6]. RGC, SMK and DS are consultant to, and have equity in, LEXEO Therapeutics which has an option to license this intellectual property and data from Cornell University. This does not alter our adherence to PLOS ONE policies on sharing data and materials
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