Pre-clinical Development of a Vaccine for the Treatment of Heroin Addiction

DESCRIPTION provided by applicant Heroin and related opioids are highly addictive drugs known for their analgesic properties Since the number of heroin users in the United States has skyrocketed reaching epidemic levels Abuse of prescription opioid pain relievers oxycodone Oxycotin and hydrocodone Vicodin which are known gateway drugs to heroin has also increased dramatically Because opioids present a significant abuse liability new therapies are needed to combat the rapid rise in opioid dependence especially since traditional pharmacological treatments such as methadone fall short at preventing relapse Immunotherapy in the form of a conjugate vaccine is a promising new therapy for opioid addiction In previous work we demonstrated that a heroin keyhole limpet hemocyanin KLH conjugate formulated with alum adjuvant generated a high titer antibody response against heroin in mice and rats Moreover in rodents we showed that anti opioid antibodies elicited by this vaccine bound heroin and its metabolites in the blood with high specificity and affinity thus
safely mitigating the psychoactive effects of heroin without binding to endogenous receptors As a result our heroin vaccine was able to block heroin self administration of dependent rats in many addiction models including conditioned place preference reinstatement and reacquisition Dose response heroin analgesia testing in mice revealed that this vaccine was able to shift EC of heroin fold however we have since improved our vaccine to produce a massive andgt fold heroin EC shift Furthermore we tested the long term performance of our optimized vaccine showing that it retains heroin immunoantagonism up to months post vaccination Our studies have indicated that this heroin vaccine is safe effective and long lasting The highly
promising nature of our vaccine for treating heroin addiction warrants further preclinical development In this STTR Fast Track application we propose to select a lead heroin vaccine candidate for advancement to clinical evaluation and conduct the IND enabling activities necessary to initiate clinical studies PUBLIC HEALTH RELEVANCE Drug abuse is the leading preventable cause of death in the United States and despite the overwhelming body of knowledge that links drug abuse with numerous diseases crime statistics and medical costs existing cessation therapies are largely unsuccessful A new type of therapy in the form of a vaccine appears to be on the horizon but existing clinical candidates have so far failed to offer broad protection This application propose to use to develop a vaccine for treatment of heroin dependence and to prevent death from heroin overdose Successful achievement of the proposed studies would thus be of significant benefit to public health