Production of a Nanoparticle Vaccine to Aid in Smoking Cessation

生产有助于戒烟的纳米颗粒疫苗

• 批准号: 10006930
• 负责人: Sean K Whittier
• 金额: $ 22.01万
• 依托单位: HAFION, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10006930
• 关键词: Address; Adjuvant; Affinity; American Cancer Society; Animal Model; Animal Testing; Animals; Antibodies; Antibody Affinity; Antibody Avidity; Antibody Formation; Antigens; Antismoking; Avidity; Biotechnology; Carrier Proteins; Cessation of life; Chantix; Clinical Trials; Complex; Custom; Dendritic Cells; Development; Dose; Drug Targeting; Effectiveness; Enzyme-Linked Immunosorbent Assay; Exhibits; Glycoproteins; Goals; Haptens; Human; Hyaluronic Acid; Immune response; Immunologic Memory; Individual; Infection; Interferometry; Kansas; Laboratories; Life; Link; Mediating; Methods; Mus; Nature; Nicotine; Operative Surgical Procedures; Pharmaceutical Chemistry; Phase; Physiological; Physiology; Positioning Attribute; Preparation; Production; Protein Glycosylation; Proteins; Publishing; Rattus; Recombinant Proteins; Research; Research Personnel; Rodent; Rodent Model; Salmonella; Salmonella Vaccines; Salmonella enterica; Serotyping; Small Business Innovation Research Grant; Smoker; Smoking; Structure; Structure of germinal center of lymph node; Subunit Vaccines; Techniques; Technology; Testing; Tobacco use; Type III Secretion System Pathway; United States; Universities; Vaccines; Woman; Work; antigen L; blood-brain barrier crossing; cost effective; design; effective intervention; efficacy testing; experience; immunogenicity; improved; in vivo; large scale production; lymph nodes; men; mouse model; nanoparticle; nicotine use; nicotine vaccine; novel; novel vaccines; pathogen; pathogenic bacteria; preservation; prevent; professor; protein structure function; side effect; smoking cessation; success; trafficking; uptake; vaccine candidate; vaccine development; vaccine efficacy; vaccine evaluation

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.

摘要 抗体介导的疗法是当前戒烟策略的一个有吸引力的替代方案，因为 抗体以药物本身为靶点，防止其越过血脑屏障，同时表现出更少的副作用 效果。到目前为止，尼古丁疫苗由于免疫原性低，在临床试验中取得的成功有限。 像大多数亚单位疫苗一样，由于它们的单体性质，它们历来效力不佳。我们的 该方法通过使用Hafion的多价佐剂融合技术(HAF)克服了这一限制，其中 最佳大小的透明质酸(HA)被连接到亚单位疫苗上以产生多价HA抗原 设计用于树突状细胞摄取并随后运输到淋巴生发中心的纳米颗粒 节点，以激发最大的免疫记忆。这项提议将把来自 Hafion LLC、Design-Zyme LLC和堪萨斯大学。我们将共同努力，把最近取得的成功结合起来 尼古丁半抗原、自我调节亚单位抗原和形成形成尼古丁的纳米颗粒 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诱发对尼古丁的免疫记忆。为了做到这一点，哈菲恩正在结合(1) 一种定制的尼古丁半抗原，它将(2)连接到我们的专有佐剂+HA复合体，已知可诱导 免疫记忆(Design-Zyme LLC)通过(3)附着一种载体蛋白抗原，赋予广泛的 对多种沙门氏菌血清型的保护。肠杆菌携带蛋白抗原是一种亚单位疫苗 由采摘实验室开发。这种SBIR的目标是创造一种安全、有效的尼古丁疫苗 适用于动物试验和最终用于FDA临床试验的额外细菌病原体保护。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其可行性 然后对尼古丁和沙门氏菌的有效性、抗体亲和力和长期免疫原性进行测试 在第一阶段，这项提议的第二阶段将包括为临床试验准备候选疫苗的研究。 作为使用GLP和GMP实践的大规模生产的解决方案。