# Clinical Assessment of Anti-cocaine Vaccine dAdGNE in Cocaine Addicts

> **NIH NIH U01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $534,128

## Abstract

Abstract. Cocaine addiction is a major problem for which there is no effective therapy. Because
addiction is a chronic relapsing illness, characterized by cycles of drug use and abstinence,
vaccination against cocaine could be an effective therapeutic. The challenge in developing an anti-
cocaine vaccine is that cocaine is a small molecule, invisible to the immune system. Attempts to link
cocaine as a hapten to a protein carrier has had limited success, likely because the protein carrier
has not been sufficiently immunogenic to evoke high affinity, high titer antibodies sufficient to block
cocaine from reaching its receptors in the brain. We have developed a novel strategy leveraging the
knowledge that adenovirus (Ad) capsid proteins are highly immunogenic in humans. We
hypothesized that linking a cocaine analog to Ad capsid proteins would elicit high-affinity,
high-titer antibodies against cocaine, sufficient to sequester systemically administered drug
from access to the brain, with consequent reduction in cocaine-induced behavior. We
strategized that we could avoid any risk of the infectious virus by disrupting the Ad, with the concept
that a vaccine comprised of the cocaine analog coupled to disrupted capsid proteins would retain the
immunologic adjuvant properties of intact Ad. Based on these concepts, we developed dAd5GNE, a
disrupted E1‾E3‾ serotype 5 Ad with GNE, a stable cocaine analog, covalently linked to the Ad
capsid. In mice, rats and nonhuman primates, dAd5GNE evoked persistent, high titer, high affinity IgG
anti-cocaine antibodies. dAd5GNE vaccination was highly effective in: abrogating cocaine-induced
hyperactivity in mice; limiting both hyperactivity and cocaine self-administration behavior in rats; and
blocking cocaine access to its cognate CNS receptors and suppressing cocaine self-administration in
nonhuman primates. With NIDA grant U01 DA033835, we developed methods to manufacture
dAd5GNE vaccine in our GMP facility, produced clinical-grade dAd5GNE for a clinical study, executed
IND-enabling preclinical efficacy and safety testing of the dAd5GNE product, submitted an IND
package, gained approval from the FDA and other regulatory groups to initiate a phase I clinical trial,
and carried out an initial clinical trial of the low dose cohort (100 μg, 6 monthly doses) in cocaine
addicts. The data from this cohort demonstrated that at this low dose, the dAd5GNE vaccine is safe
and elicits persistent serum cocaine-specific antibodies in the range approaching that which should
be efficacious. The focus of the present proposal is to complete the FDA and IRB approved clinical
trial with 2 higher doses (cohort 2: 316 µg/dose and cohort 3: 1,000 µg/dose; each for 6 monthly
doses). Specific aim. Initiate and complete cohorts 2 and 3 of the clinical trial to assess the
safety and preliminary measure of efficacy of the dAd5GNE vaccine in cocaine addicts.

## Key facts

- **NIH application ID:** 9853773
- **Project number:** 5U01DA048524-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** RONALD G CRYSTAL
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $534,128
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853773

## Citation

> US National Institutes of Health, RePORTER application 9853773, Clinical Assessment of Anti-cocaine Vaccine dAdGNE in Cocaine Addicts (5U01DA048524-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9853773. Licensed CC0.

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