Tunable Nicotine DNA-Nanovaccines

描述(申请人提供)：通过免疫学家、有机化学家、纳米结构化学家和神经学家的多学科互动和合作，我们将采用自下而上的策略，以可控的方式将尼古丁半抗原、T辅助细胞肽和佐剂设计到自组装的DNA纳米支架上，以诱导T细胞依赖的抗尼古丁抗体反应。各种抗原组分在DNA-纳米支架上的强健和多功能的合成和组装，以及逐步筛选，为识别纳米疫苗的“最佳组合和配置”提供了机会，以诱导强烈的抗尼古丁抗体反应，导致生产用于治疗尼古丁依赖的高滴度和高亲和力的抗尼古丁抗体。可以想象，这种方法可以很容易地扩展到任何疫苗的开发，包括那些针对滥用药物、微生物病原体和肿瘤抗原的疫苗。因此，该项目代表了对疫苗构建中一种新的非常规技术的概念验证调查。 公共卫生相关性：我们建议开发针对尼古丁的新型DNA纳米疫苗。通过合理的设计和循序渐进的筛选，我们的目标是创造有效的尼古丁疫苗来治疗尼古丁依赖，以实现减少烟草相关疾病的长期目标。

DESCRIPTION (provided by applicant): Through multidisciplinary interactions and collaborations involving immunologists, organic chemists, nanostructural chemists and neuroscientists, we will employ a bottom-up strategy to engineer nicotine hapten, T helper cell peptides and adjuvant onto self-assembling DNA nanoscaffolds in a controllable fashion to induce T-cell dependent anti-nicotine antibody responses. Robust and versatile synthesis and assembly of various antigenic components onto DNA-nanoscaffolds along with step-wise screening afford opportunities to identify "optimal combinations and configurations" of the nanovaccine for the induction of strong, anti-nicotine antibody responses, leading to production of high titer and high affinity anti-nicotine antibodies for treatment of nicotine dependence. It is conceivable that this approach can be readily extended to the development of any vaccines, including those targeting drugs of abuse, microbial pathogens and tumor antigens. Thus, the project represents a proof-of-concept investigation of a new and unconventional technology in vaccine construction. PUBLIC HEALTH RELEVANCE: We propose to develop novel DNA nanovaccines against nicotine. Through rational design and step-wise screenings, we aim to create effective nicotine vaccines to treat nicotine dependence toward a longer-term goal of reducing tobacco-related diseases.