Adenovirus-based Nanoparticle Vaccines

描述（由申请人提供）：在过去的四分之一世纪中，“治疗性疫苗”的概念已经从最初的针对微生物病原体的免疫的狭义扩大到目前的可以刺激有益免疫应答的任何治疗的广义。因此，科学家和医生现在正试图开发针对肿瘤和成瘾药物等深奥目标的“疫苗”。后一类包括尼古丁疫苗。尼古丁疫苗的原理是，循环中的抗尼古丁抗体将在尼古丁到达其生理靶点所在的大脑之前拦截血液中的尼古丁。临床前和临床试验数据已经支持尼古丁疫苗可以减少吸烟的生理效应并降低戒烟后重新对尼古丁成瘾的可能性。在尼古丁疫苗开发的同时，疫苗运载工具也取得了进展。在这些进展中，人们认识到，作为小颗粒（直径为40至100亿分之一米的“纳米颗粒”）递送的疫苗和由病毒递送的疫苗比由可溶性蛋白递送的疫苗更有效。本申请中的中心概念是病毒，特别是腺病毒，由于它们的大小（80亿分之一米）和它们作为其感染周期的一部分与细胞表面相互作用的能力，代表了特别有效的纳米颗粒疫苗形式。本申请试图将基于腺病毒的疫苗的功效与尼古丁作为靶标的重要性联合收割机结合，并将测试尼古丁与腺病毒胱天蛋白的直接共价缀合将产生能够产生治疗相关水平的抗尼古丁抗体的高效疫苗的假设。 公共卫生相关性：项目叙述。最近的研究表明，如果疫苗以微小颗粒（纳米颗粒）而不是可溶性蛋白质的形式递送，它们会更有效。目前的研究将测试腺病毒，一种大约80亿分之一米宽的纳米颗粒，是否可以用来创造一种新的，甚至更有效的纳米颗粒疫苗。研究将集中在尼古丁疫苗上，这可能有助于吸烟者戒烟。

DESCRIPTION (provided by applicant): 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 to 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 application 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 application 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. PUBLIC HEALTH RELEVANCE: Project Narrative. Recent studies suggest that vaccines are more effective if they are delivered as tiny particles (nanoparticles) instead of soluble proteins. The present study will test whether adenovirus, a nanoparticle that is approximately 80 billionths of a meter wide, can be used to create a new, even more effective class of nanoparticle vaccines. Studies will focus on a vaccine against nicotine, which may help smokers to quit smoking.