Abstract
The challenge in developing an anti-cocaine vaccine is that cocaine is a small molecule, invisible to the immune system. Leveraging the knowledge that adenovirus (Ad) capsid proteins are highly immunogenic in humans, we hypothesized that linking a cocaine hapten to Ad capsid proteins would elicit high-affinity, high-titer antibodies against cocaine, sufficient to sequester systemically administered cocaine and prevent access to the brain, thus suppressing cocaine-induced behaviors. 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 proteins. In pre-clinical studies, dAd5GNE evoked persistent, high titer, high affinity IgG anti-cocaine antibodies, and was highly effective in blocking cocaine-induced hyperactivity and cocaine self-administration behavior in rats. Future studies will be designed to expand the efficacy studies, carry out relevant toxicology studies, and test dAd5GNE in human cocaine addicts.
Keywords: dAd5GNE, Cocaine, Addiction, Adenovirus, Vaccine, Anti-coccaine antibody, passive immunity, keyhole limpet hemocyanin, EDC, E1-E3-, Sensory nerve action potential, Palmitoylethanolamide, Laser evoked potential
CNS & Neurological Disorders - Drug Targets
Title: Anti-Cocaine Vaccine Based on Coupling a Cocaine Analog to a Disrupted Adenovirus
Volume: 10 Issue: 8
Author(s): George Koob, Martin J. Hicks, Sunmee Wee, Jonathan B. Rosenberg, Bishnu P. De, Stephen M. Kaminksy, Amira Moreno, Kim D. Janda and Ronald G. Crystal
Affiliation:
Keywords: dAd5GNE, Cocaine, Addiction, Adenovirus, Vaccine, Anti-coccaine antibody, passive immunity, keyhole limpet hemocyanin, EDC, E1-E3-, Sensory nerve action potential, Palmitoylethanolamide, Laser evoked potential
Abstract: The challenge in developing an anti-cocaine vaccine is that cocaine is a small molecule, invisible to the immune system. Leveraging the knowledge that adenovirus (Ad) capsid proteins are highly immunogenic in humans, we hypothesized that linking a cocaine hapten to Ad capsid proteins would elicit high-affinity, high-titer antibodies against cocaine, sufficient to sequester systemically administered cocaine and prevent access to the brain, thus suppressing cocaine-induced behaviors. 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 proteins. In pre-clinical studies, dAd5GNE evoked persistent, high titer, high affinity IgG anti-cocaine antibodies, and was highly effective in blocking cocaine-induced hyperactivity and cocaine self-administration behavior in rats. Future studies will be designed to expand the efficacy studies, carry out relevant toxicology studies, and test dAd5GNE in human cocaine addicts.
Export Options
About this article
Cite this article as:
Koob George, J. Hicks Martin, Wee Sunmee, B. Rosenberg Jonathan, P. De Bishnu, M. Kaminksy Stephen, Moreno Amira, D. Janda Kim and G. Crystal Ronald, Anti-Cocaine Vaccine Based on Coupling a Cocaine Analog to a Disrupted Adenovirus, CNS & Neurological Disorders - Drug Targets 2011; 10 (8) . https://dx.doi.org/10.2174/187152711799219334
DOI https://dx.doi.org/10.2174/187152711799219334 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Human T-Cell Lymphotropic Virus in Patients Infected with HIV-1: Molecular Epidemiology and Risk Factors for Transmission in Piaui, Northeastern Brazil
Current HIV Research Editorial: (Thematic Issue) Novel Concepts on the Blood-Brain Barrier and Brain Pathology. New Therapeutic Approaches
CNS & Neurological Disorders - Drug Targets Clinical Aspects of Melatonin Intervention in Alzheimers Disease Progression
Current Neuropharmacology Redox-inactive Analogue of Tocotrienol as a Potential Anti-cancer Agent
Anti-Cancer Agents in Medicinal Chemistry SYNTHESIS AND APPLICATIONS OF Fe3O4/SiO2 CORE-SHELL MATERIALS
Current Pharmaceutical Design Cell Type Specific Redox Status is Responsible for Diverse Electromagnetic Field Effects
Current Medicinal Chemistry Does Phosphodiesterase 11A (PDE11A) Hold Promise as a Future Therapeutic Target?
Current Pharmaceutical Design Emerging and Alternative Therapies For Parkinson Disease: An Updated Review
Current Pharmaceutical Design Inhibition of Amyloid Fibrillation by Small Molecules and Nanomaterials: Strategic Development of Pharmaceuticals Against Amyloidosis
Protein & Peptide Letters Does the Cholinesterase Inhibitor, Donepezil, Benefit Both Declarative and Non-Declarative Processes in Mild to Moderate Alzheimers Disease?
Current Alzheimer Research New Insights into the Molecular Resistance Mechanisms of Chronic Myeloid Leukemia
Current Cancer Drug Targets Ghrelin in Central Neurons
Current Neuropharmacology Discovery of New Potential Antimalarial Compounds Using Virtual Screening of ZINC Database
Combinatorial Chemistry & High Throughput Screening Nanotechnology Applications for Diffuse Intrinsic Pontine Glioma
Current Neuropharmacology An Introduction to Obesity and Dementia
Current Alzheimer Research Aspirin: from a Historical Perspective
Recent Patents on Cardiovascular Drug Discovery Current Developments for the Diagnosis and Treatment of Irritable Bowel Syndrome
Current Pharmaceutical Design Cytokines and Chemokines as Regulators of Angiogenesis in Health and Disease
Current Pharmaceutical Design A Short Historical Survey of Developments in Amyloid Research
Protein & Peptide Letters Fibrillar β-Amyloid Impairs the Late Phase of Long Term Potentiation
Current Alzheimer Research