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: 10194440
• 负责人: Sean K Whittier
• 金额: $ 12.89万
• 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 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10194440
• 关键词: Address; Adjuvant; Affinity; American Cancer Society; Animal Model; Animal Testing; Animals; Antibodies; Antibody Affinity; Antibody Avidity; Antibody Formation; Antibody-mediated protection; 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 intervention; design; 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.

概括 抗体介导的疗法是当前戒烟策略的有吸引力的替代品，因为 抗体针对药物本身，以防止其越过血脑屏障，而表现出较少的一面 效果。迄今为止，由于免疫原性低，尼古丁疫苗在临床试验中取得了有限的成功。 像大多数亚基疫苗一样，由于其单体性质，它们历史上的效率较差。我们的 通过使用Hafion的多价调整融合技术（HAF）来克服此限制的方法 将最佳尺寸的透明质酸（HA）偶联到亚基疫苗，以产生多价HA抗原 纳米颗粒专为树突状细胞摄取，随后运输到淋巴的生发中心 节点以引起最大的免疫记忆。该提议将把来自 Hafion LLC，Design-Zyme LLC和堪萨斯大学。一起，我们将结合最近的成功 尼古丁触觉，自我添加亚基抗原和形成纳米颗粒以发展尼古丁 提供长期免疫记忆的疫苗。我们的方法改进了当前的设计 尼古丁疫苗是有目的地引起尼古丁的免疫记忆的。为此，Hafion正在结合（1） （2）与我们专有的调整 + HA复合物相关的定制尼古丁触觉 免疫记忆（Design-Zyme LLC）通过（3）供认广泛的载体蛋白抗原的附着 保护多种沙门氏菌血清型。 S. enterica载体蛋白抗原是亚基疫苗 由采摘实验室开发。该SBIR的目的是与 其他细菌病原体保护适用于动物测试和最终在FDA临床试验中使用。这 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 然后将测试针对尼古丁和沙门氏菌的效率，抗体亲和力和长期免疫原性 在第一阶段中，该提案的第二阶段将涉及研究以准备临床试验的疫苗候选者 作为使用GLP和GMP实践来解决更大规模的生产。