Production of a Nanoparticle Vaccine to Aid in Smoking Cessation

总结 抗体介导的疗法是目前戒烟策略的一种有吸引力的替代方案， 抗体针对药物本身，以防止其穿过血脑屏障，同时表现出更少的副作用， 方面的影响.迄今为止，尼古丁疫苗由于其低免疫原性而在临床试验中取得了有限的成功。 像大多数亚单位疫苗一样，由于它们的单体性质，它们在历史上具有较差的功效。我们 一种方法通过使用Hafion的多价佐剂融合技术（Haf）克服了这一限制，其中 将最佳大小的透明质酸（HA）与亚单位疫苗缀合以产生多价HA抗原 设计用于被树突细胞摄取并随后运输到淋巴中的生发中心的纳米颗粒 以激发最大免疫记忆该提案将汇集来自以下国家的高级调查员 Hafion LLC、Design-Zyme LLC和堪萨斯大学。我们将联合收割机结合最近的成功 尼古丁半抗原，自噬亚单位抗原和纳米颗粒的形成， 提供长期免疫记忆的疫苗。我们的方法改进了当前的设计， 尼古丁疫苗通过有目的地引发对尼古丁的免疫记忆。为此，Hafion正在结合（1） 定制的尼古丁半抗原，其将（2）与我们的专有佐剂+HA复合物连接，已知其引起 免疫记忆（Design-Zyme LLC），通过（3）附着赋予广泛免疫记忆的载体蛋白抗原， 针对多种沙门氏菌血清型的保护。色葡萄肠道载体蛋白抗原是一种亚单位疫苗， 由采摘实验室开发。该SBIR的目标是创造一种安全，有效的尼古丁疫苗， 额外的细菌病原体保护，适用于动物试验和最终用于FDA临床试验。这 该项目将通过组装完整的尼古丁+沙门氏菌疫苗纳米颗粒来证明可行性， 然后将测试对尼古丁和沙门氏菌的功效、抗体亲和力和长期免疫原性 在第一阶段该提案的第二阶段将包括为临床试验准备候选疫苗的研究 使用GLP和GMP实践解决更大规模的生产。

SUMMARY Antibody-mediated therapies are an attractive alternative to current smoking cessation strategies because antibodies target the drug itself to prevent its crossing the blood brain barrier while exhibiting far fewer side effects. To date, nicotine vaccines have met with limited success in clinical trials due to their low immunogenicity. Like most subunit vaccines, they have historically suffered from poor efficacy due to their monomeric nature. Our approach overcomes this limitation by using Hafion’s polyvalent adjuvant fusion technology (Haf) wherein optimally sized hyaluronic acid (HA) is conjugated to a subunit vaccine to create a polyvalent HA-antigen nanoparticle designed for uptake by dendritic cells and subsequent trafficking to germinal centers in the lymph nodes to elicit maximum immunological memory. This proposal will bring together senior investigators from Hafion LLC, Design-Zyme LLC, and the University of Kansas. Together, we will combine the recent successes of a nicotine hapten, a self-adjuvating subunit antigen and the formation of nanoparticles to develop a nicotine vaccine that provides long-term immunological memory. Our approach improves upon the current design of nicotine vaccines by purposefully eliciting immunological memory to nicotine. To do this, Hafion is combining (1) a customized nicotine hapten that will be (2) linked to our proprietary adjuvant + HA complex known to elicit immunological memory (Design-Zyme LLC) by (3) the attachment of a carrier protein antigen that confers broad protection against multiple Salmonella serotypes. The S. enterica carrier protein antigen is a subunit vaccine developed by the Picking Laboratory. The goal of this SBIR is to create a safe, effective nicotine vaccine with additional bacterial pathogen protection suitable for animal testing and eventual use in FDA clinical trials. This project will demonstrate feasibility by assembling complete nicotine + Salmonella vaccine nanoparticles which will then be tested for efficacy, antibody affinity and long-term immunogenicity against nicotine and Salmonella in Phase I. Phase II of this proposal will involve studies to prepare the vaccine candidate for clinical trials as well as address larger scale production using GLP and GMP practices.