Laser Adjuvant for Nicotine Vaccines

描述（由申请人提供）：该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。本提案的具体目的是提供概念证明证据，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诱导作为一种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，但其疗效远不能令人满意，因为即使在多次接种后，NicAb的产生水平也不足，并且接种个体的血清NicAb浓度差异很大。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，几乎没有副作用，针对一种模型蛋白抗原，小鼠卵清蛋白。我们的研究表明，在免疫前，用高重复、纳秒脉冲、非破坏性可见光对一小块皮肤进行短暂（1~2分钟）照射，可以增强抗原提呈细胞的移动性和抗原摄取，使体液免疫反应比单独注射抗原提高500%。在本提案中，我们将在小鼠和小型猪身上测试这种打破范式的方法是否能显著增强和维持现有尼古丁疫苗引起的NicAb的产生。我们还将测试激光和明矾佐剂对NicAb生产的潜在添加剂或协同效应。该开发的基于激光的疫苗佐剂平台有望很容易地转移到临床，因为在这种设置下的激光已经在临床中广泛用于各种美容和治疗目的了十年。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，而且还将为其他预防性和免疫治疗性疫苗的有效免疫反应开辟新的途径，对公众健康产生重大影响。诱导尼古丁特异性抗体（NicAb）作为一种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。进一步提高尼古丁疫苗激光佐剂治疗吸烟成瘾的疗效，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.