Production of a Nanoparticle Vaccine to Aid in Smoking Cessation

生产有助于戒烟的纳米颗粒疫苗

基本信息

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
项目类别：
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

项目摘要

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方案，因为抗体以药物本身为目标，以防止其穿过血脑屏障，同时表现出更少的副作用迄今为止，尼古丁疫苗由于其免疫原性低，在临床试验中取得的成功有限。与大多数亚单位疫苗一样，由于其单体性质，它们历来效力不佳。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。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状细胞摄取并随后运输至淋巴生发中心的纳米颗粒该提案将汇集来自各领域的高级研究人员。 Hafion LLC、Design-Zyme LLC 和堪萨斯大学将共同结合最近的成功。尼古丁半抗原、自我辅助亚基抗原的形成以及纳米颗粒的形成以开发尼古丁我们的方法改进了目前的设计。通过有目的地引发对尼古丁的免疫记忆来开发尼古丁疫苗为此，Hafion 正在结合 (1)。定制的尼古丁半抗原，将 (2) 连接到我们已知可引发的专有佐剂 + HA 复合物免疫记忆（Design-Zyme LLC）通过（3）附着载体蛋白抗原，赋予广泛的记忆针对多种沙门氏菌血清型的保护肠沙门氏菌载体蛋白抗原是一种亚单位疫苗。该 SBIR 的目标是开发一种安全、有效的尼古丁疫苗。额外的细菌病原体保护适用于动物测试并最终用于 FDA 临床试验。该项目将通过组装完整的尼古丁+沙门氏菌疫苗纳米粒子来证明可行性然后将测试针对尼古丁和沙门氏菌的功效、抗体亲和力和长期免疫原性该提案的第二阶段将涉及为临床试验准备候选疫苗的研究使用 GLP 和 GMP 实践解决大规模生产问题。