Adenovirus-based Nanoparticle Vaccines

抽象的。 在过去的四分之一个世纪里，“治疗性疫苗”的概念已经扩大。 从最初狭义的针对微生物病原体的免疫到 目前，任何可以激发有益免疫的治疗方法的广泛含义 回应。因此，科学家和内科医生现在正试图开发“疫苗”。 针对肿瘤和成瘾药物等深奥的目标。后一类 包括针对尼古丁的疫苗。尼古丁疫苗的逻辑是循环中的反- 尼古丁抗体将在尼古丁到达大脑之前拦截血液中的尼古丁 它的生理目标驻留在。已经，临床前和临床试验数据支持 尼古丁疫苗可以减少吸烟和吸烟的生理影响 减少戒烟后重新对尼古丁上瘾的可能性。在……里面 随着尼古丁疫苗的发展，在尼古丁疫苗方面取得了进展 疫苗的运送工具。在这些进展中，有一点是认识到疫苗 以小颗粒(从40到100亿分之一米的范围内的“纳米颗粒”)的形式提供 直径)，由病毒运送的疫苗比疫苗更有效 由可溶性蛋白质传递。该提案中的一个中心概念是病毒，并且在 特别是腺病毒，代表了一种特别有效的纳米颗粒疫苗。 由于它们的大小(80亿分之一米)和它们与细胞表面相互作用的能力 作为它们感染周期的一部分。这项建议旨在将以下各项的功效结合起来 以尼古丁为靶标的腺病毒疫苗，将测试 假设尼古丁与腺病毒caspid的直接共价偶联将 产生一种高效的疫苗，能够产生与治疗相关的 抗尼古丁抗体水平。

Abstract. Over the past quarter century, the concept of "therapeutic vaccines" has broadened from the initial, narrow meaning of a immunization against a microbial pathogen to the current, broad meaning of any treatment that can stimulate a beneficial immune response. As a result, scientists and physicians are now trying develop "vaccines" against such esoteric targets as tumors and drugs of addiction. The latter category includes vaccines against nicotine. The logic of a nicotine vaccine is that circulating anti- nicotine antibodies will intercept nicotine in the blood before it reaches the brain where its physiologic target resides. Already, pre-clinical and clinical trial data support the concept that nicotine vaccines can reduce the physiologic effects of smoking and reduce the likelihood of regaining an addiction to nicotine after smoking cessation. In parallel with the development of nicotine vaccines, there have been advances in the delivery vehicles for vaccines. Among these advances is the recognition that vaccines delivered as small particles ("nanoparticles" ranging from 40 to 100 billionths of a meter in diameter) and vaccines delivered by viruses are more efficacious than vaccines delivered by soluble proteins. A central concept in this proposal is that viruses, and in particular, adenoviruses, represent an especially effective form of nanoparticle vaccines due to their size (80 billionths of a meter) and their ability to interact with the cell surface as part of their infection cycle. This proposal seeks to combine the efficacy of adenovirus-based vaccines with the importance of nicotine as a target and will test the hypothesis that direct covalent conjugation of nicotine to the adenovirus caspid will result in a highly effective vaccine that is capable of generating therapeutically relevant levels of anti-nicotine antibodies.