Adenovirus-based Nanoparticle Vaccines

基于腺病毒的纳米颗粒疫苗

• 批准号: 8267684
• 负责人: Stephen Michael Kaminsky
• 金额: $ 36.52万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8267684
• 关键词: Adenoviruses; Adjuvant; Adult; Affinity; Antibodies; Antigens; Avidity; B-Lymphocytes; Behavioral; Binding; Blood; Brain; Caliber; Capsid; Carrier Proteins; Categories; Cell Nucleus; Cell Surface Receptors; Cell surface; Cells; Chemicals; Chronic Bronchitis; Cigarette; Clinical; Clinical Trials; Cocaine; Coronary heart disease; Data; Dendritic Cells; Development; Dose; Drug Addiction; Engineering; Evaluation; Exhibits; Genes; Genetic; Genome; Goals; Haptens; Health Priorities; Healthcare; Heroin; Humoral Immunities; Immune response; Immunity; Immunization; Immunomodulators; In Vitro; Infection; Inflammation; Intercept; Interleukin-15; Link; Logic; Malignant neoplasm of lung; Morphine; Mus; Nicotine; Oxidants; Peptide Vaccines; Physicians; Physiological; Property; Proteins; Pulmonary Emphysema; Rattus; Reporting; Risk; Scientist; Serum; Smoker; Smoking; Specificity; Stroke; Surgeon; T-Lymphocyte; TNFSF5 gene; Testing; Time; Transgenes; United States; United States National Center for Health Statistics; Vaccination; Vaccines; Virus; Virus-like particle; Work; abstracting; addiction; adenovirus receptor; analog; base; cigarette smoking; cigarette smoking; cost; efficacy testing; fighting; global health; immunogenic; improved; in vitro Assay; in vivo; meter; microbial; mouse model; nanoparticle; particle; pathogen; pre-clinical; preclinical study; prevent; response; small molecule; smoking cessation; therapeutic vaccine; trafficking; tumor; vector

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.

抽象的。 在过去的四分之一世纪中，“治疗性疫苗”的概念已经扩大 从最初对微生物病原体的狭义免疫到 目前，广泛的意义上的任何治疗，可以刺激有益的免疫 反应因此，科学家和医生们正在努力开发“疫苗”。 针对肿瘤和成瘾药物等深奥的目标。后一类 包括尼古丁疫苗。尼古丁疫苗的原理是， 尼古丁抗体会在尼古丁到达大脑之前拦截血液中的尼古丁， 它的生理目标所在。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， 减少戒烟后重新对尼古丁上瘾的可能性。在 与尼古丁疫苗的开发同时， 疫苗的运输工具。在这些进展中，人们认识到疫苗 作为小颗粒（“纳米颗粒”，范围从40到100十亿分之一米 直径），并且由病毒递送的疫苗比疫苗更有效 由可溶性蛋白质传递。该提案的一个中心概念是，病毒， 特别是腺病毒，代表了一种特别有效的纳米颗粒疫苗形式 由于它们的大小（80十亿分之一米）和它们与细胞表面相互作用的能力， 作为感染循环的一部分该提案旨在将以下功效联合收割机 以尼古丁为靶点的腺病毒疫苗，并将测试 假设尼古丁与腺病毒Caspid直接共价结合将 导致能够产生治疗相关的 抗尼古丁抗体水平