VACCINATION FOR TREATMENT OF NICTOTINE DEPENDENCE

已经开发了尼古丁疫苗（NincVax或3 '-免疫原），其在实验动物中激发高滴度的尼古丁特异性抗体。对大鼠进行免疫接种可显著降低尼古丁剂量到达大脑的部分，防止尼古丁诱导的血压升高，防止尼古丁诱导的兴奋活动刺激，并抑制与尼古丁依赖相关的介导行为的缓解。在临床相关尼古丁剂量下观察到这些效应，并且尼古丁特异性IgG滴度应在人体中达到。目前的提案是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，评估尼古丁疫苗接种作为尼古丁依赖的潜在治疗方法。评价尼古丁疫苗接种作为尼古丁依赖潜在治疗方法的个体和人体临床研究。SPIRCAP应用程序的各个组成部分是1）临床研究和血清学检测的开发和生产（Fattom，Nabi，Rockville博士），2）大鼠接种疫苗的行为研究（Malin，U。Houston-Clear Lake），3）大鼠中疫苗接种的药代动力学和其他行为研究（Pentel博士，明尼阿波利斯医学研究基金会）和4）疫苗接种的I/II期和III期临床试验（Hatsukami博士，U.明尼苏达州）。一个行政核心将为项目提供全面协调和行政支持（Scott Winston博士，Nabi，Rockville）。此外，尼古丁疫苗的毒理学研究将根据与NIDA的单独合同进行。SPIRCAP的这一组成部分旨在：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）准备并提交用于人体临床研究的IND 4）对临床前和临床样本进行血清学检测5）进行临床研究中心和数据监测，以支持人体临床研究

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