VACCINATION FOR TREATMENT OF NICTOTINE DEPENDENCE

已经研制出一种尼古丁疫苗（NincVax或3'-免疫原），可在实验动物中引起高滴度的尼古丁特异性抗体。大鼠免疫可显著降低尼古丁剂量到达大脑的比例，防止尼古丁引起的血压升高，防止尼古丁引起的运动活动刺激，抑制与尼古丁依赖相关的介导行为的缓解。这些影响是在临床相关的尼古丁剂量和尼古丁特异性IgG滴度下观察到的，在人类中应该是可以实现的。目前的提案是该SPIRCAP申请的四个组成部分之一，其目的是进行后期临床前和人体临床研究，评估尼古丁疫苗作为尼古丁依赖的潜在治疗方法。个体和人类临床研究评估接种尼古丁疫苗作为尼古丁依赖的潜在治疗方法。SPIRCAP申请的各个组成部分是1)临床研究和血清学测试的开发和制造（Fattom博士，Nabi, Rockville）， 2)大鼠疫苗接种的行为研究（Malin博士，U. Houston-Clear Lake）， 3)大鼠疫苗接种的药代动力学和其他行为研究（Pentel博士，Minneapolis医学研究基金会）和4)疫苗接种的I/II和III期临床试验（Hatsukami博士，U. Minnesota）。行政核心将为该项目提供全面协调和行政支助（斯科特·温斯顿博士，纳比，罗克维尔）。此外，尼古丁疫苗的毒理学研究将根据与NIDA签订的另一份合同进行。该部分的目的是：1)生产两个临床批次的NicVax 2)进行临床前安全性和毒理学研究3)准备并提交用于人类临床研究的IND 4)对临床前和临床样品进行血清学测试5)进行临床现场和数据监测以支持人类临床研究

A nicotine vaccine (NincVax or 3'-immunogen) has been developed which elicits high titers of nicotine-specific antibodies in experimental animals. Immunization of rats substantially reduces the fraction of a nicotine dose reaching the brain, prevents nicotine-induced increases in blood pressure, prevents nicotine-induced stimulation of locomoter activity, and inhibits the relief of mediated behaviors relevant to nicotine dependence. These effects are observed at clinically relevant nicotine doses, and with nicotine-specific IgG titers that should be achievable in humans. The current proposal is one of four components of this SPIRCAP application, the purpose of which is to perform late preclinical and human clinical studies evaluating vaccination against nicotine as a potential treatment for nicotine dependence. The individual and human clinical studies evaluating vaccination against nicotine as a potential treatment for nicotine dependence. The individual components of the SPIRCAP application are 1) Development and manufacturing for clinical studies and serological testing (Dr. Fattom, Nabi, Rockville), 2) Behavioral studies of vaccination in rats (Dr. Malin, U. Houston-Clear Lake), 3) Pharmacokinetic and additional behavioral studies of vaccination in rats (Dr. Pentel, Minneapolis Medical Research Foundation) and 4) Phase I/II and III clinical trials of vaccination (Dr. Hatsukami, U. Minnesota). An Administrative Core will provide overall coordination and administrative support for the project (Dr. Scott Winston, Nabi, Rockville). In addition, toxicology studies of the nicotine vaccine will be performed under a separate contract with NIDA. The aims of this component of the SPIRCAP are to: 1) Manufacture two clinical lots of NicVax 2) Perform preclinical safety and toxicology studies 3) Prepare and submit IND for human clinical studies 4) Perform serological testing on preclinical and clinical samples 5) Conduct clinical site and data monitoring in support of the human clinical studies