Laser Adjuvant for Nicotine Vaccines

描述（由申请人提供）： 本申请涉及广泛的挑战领域（15）转化科学和特定的挑战主题，15-DA-101*：提高小分子疫苗免疫原性的新方法。该提案的具体目的是提供概念证据证明，新开发的激光系统可以在必要的时间内显著增加现有尼古丁疫苗引起的尼古丁特异性抗体（NicAb）的产生。NicAb诱导作为治疗烟草依赖的替代方法在临床试验中显示出很大的希望，但由于即使在多次接种疫苗后NicAb产生水平不足以及接种疫苗个体之间血清NicAb浓度的较大变化，其功效远不能令人满意。我们已经开发了一种原型激光系统，能够增强和延长体液免疫反应，副作用少，对模型蛋白抗原，卵清蛋白在小鼠。我们的研究表明，在免疫前用高重复、纳秒脉冲、非破坏性可见光短暂（1~2分钟）照射小面积皮肤，增强了抗原呈递细胞的移动性及其抗原摄取，使体液免疫应答比单独注射抗原提高高达500%。在这项提案中，我们将测试这种突破性的方法是否可以显着增强和维持现有尼古丁疫苗在小鼠和小型猪中引起的NicAb产生。我们还将测试激光和明矾佐剂对NicAb生产的潜在加和或协同效应。正在开发的基于激光的疫苗佐剂平台预计将很容易转移到临床，因为十年来，这种设置下的激光已在临床上广泛用于各种美容和治疗目的。这项临床前研究将在两年内完成，如果成功，不仅将使烟草依赖者受益，还将为其他预防性和免疫性疫苗的有效免疫应答开辟新途径，对公共卫生产生重大影响。尼古丁特异性抗体（NicAb）的诱导作为一种替代方法来治疗烟草依赖显示出巨大的前景，在临床试验。进一步提高尼古丁疫苗在激光辅助治疗吸烟成瘾中的疗效将对公众健康产生重要影响。

DESCRIPTION (provided by the applicant): This application addresses broad Challenge Area (15) Translational Science and specific Challenge Topic, 15-DA-101*: Novel Approaches to Improve Immunogenicity of Vaccine against Small Molecules. The specific aim of this proposal is to provide proof of concept evidence that a newly-developed laser system can significantly augment the production of nicotine-specific antibody (NicAb) elicited by existing nicotine vaccines for a necessary length of time. NicAb induction as an alternative approach to treat tobacco dependence shows great promise in clinical trials, but the efficacy is far from satisfying, owing to insufficient levels of NicAb production even after multiple vaccinations and large variations in the concentration of serum NicAb among vaccinated individuals. We have developed a prototype laser system capable of enhancing and prolonging humoral immune responses, with few side effects, against a model protein antigen, ovalbumin in mice. Our investigation demonstrated that a brief (1~2 mins) illumination of a small area of the skin with a high-repetition, nanosecond pulsed, non-destructive visible light prior immunization enhanced the mobility of antigen presenting cells and their antigen-uptake, boosting humoral immune responses by up to 500% over antigen injection alone. In this proposal, we will test whether this paradigm-breaking approach can significantly enhance and sustain NicAb production provoked by existing nicotine vaccines in both mice and miniature pigs. We will also test potential additive or synergistic effects between laser and alum adjuvants on NicAb production. The laser-based vaccine adjuvant platform under the development is expected to be readily moved to the clinic, because the laser at this setting has been widely used in the clinic for a variety of cosmetic and therapeutic purposes for a decade. This preclinical study will be completed in two years, which, if successful, will not only benefit tobacco dependents, but also open a new avenue to efficiently mount immune responses for other prophylactic and immunotherapeutic vaccines, having a great impact on public health. Induction of nicotine-specific antibody (NicAb) as an alternative approach to treat tobacco dependence shows great promise in clinical trials. Further improvement of the efficacy of nicotine vaccines in treatment of smoking addiction by laser-based adjuvant will have an important impact on public health.