Influenza vaccination using a microneedle patch

使用微针贴片进行流感疫苗接种

• 批准号: 8324486
• 负责人: MARK R. PRAUSNITZ
• 金额: $ 202.63万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8324486
• 关键词: Address; Adopted; Animal Model; Animals; Antibodies; Antigen Targeting; Antigen-Presenting Cells; Antigens; Cadaver; Cavia; Cells; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinic; Clinical Trials; Consultations; Contractor; Contracts; Cost Effectiveness Analysis; Dendritic Cells; Development; Devices; Dose; Drug Formulations; Drug usage; Engineering; Exhibits; Ferrets; Future; Generations; Goals; Good Clinical Practice; Hemagglutination; Hospitalization; Human; Immune response; Immune system; Immunity; Immunologics; In Vitro; Infection prevention; Influenza; Influenza vaccination; Investigational Drugs; Investigational New Drug Application; Laboratories; Legal; Licensure; Logistics; Manufacturer Name; Measurement; Measures; Mediating; Medical; Medical Economics; Methods; Monitor; Morbidity - disease rate; Mus; Needles; New Drug Approvals; Outcome; Outcomes Research; Painless; Pathway interactions; Patients; Phase I Clinical Trials; Policies; Process; Production; Prophylactic treatment; Protocols documentation; Refrigeration; Relative (related person); Route; Safety; Sagittaria; Self Administration; Self-Administered; Skin; Solid; System; Technology; Technology Transfer; Time; Universities; Vaccination; Vaccine Antigen; Vaccines; Work; analytical method; antigen processing; base; clinical practice; cost; design; experience; good laboratory practice; human study; human subject; immunogenicity; improved; in vivo; influenza virus vaccine; minimally invasive; mortality; novel; policy implication; preclinical study; public health relevance; quantum; response; seasonal influenza; social; wasting

DESCRIPTION (provided by applicant): Influenza is a major cause of morbidity and mortality worldwide. Although vaccination is the most effective Strategy to prevent infection, influenza vaccination coverage is insufficient and improved vaccine immunogenicity is needed. We propose development of a microneedle patch that is simple enough to increase vaccination coverage by enabling self-administration and specifically designed to improve immunogenicity by targeting dendritic cells in skin. Microneedles (MN) are micron-scale, solid needles that administer vaccine directly into skin using a simple, painless and minimally invasive approach. The patch is designed to enable skin vaccination with a patch application time of just seconds, generation of no sharp biohazardous waste, and antigen stability during storage without refrigeration. The goal of this milestone-driven project is to develop a MN patch for influenza vaccination and assess its safety and immunogenicity in a Phase I clinical trial. In Aim 1, based at Georgia Tech, we will design, formulate, and fabricate MN for simple, rapid application and long-term stability. In Aim 2, based at Emory, we will assess MN vaccination in three animal models with the goals of validating suitability for human trials and enhancing immunogenicity. Aim 3 will be achieved with external contractors and consultants to develop and validate cGMP manufacturing, conduct GLP preclinical studies and obtain an IND. This work will culminate in a Phase I clinical trial carried out in Aim 4 at Emory's Hope Clinic to assess safety, tolerability, immunogenicity and acceptability of influenza vaccination using a MN patch. Finally, Aim 5 will be based at PATH to assess regulatory, cost and policy issues associated with self-administered influenza vaccination. Expected outcomes from this research are (i) development of a low-cost MN patch that administers influenza vaccine in a simple, rapid manner, (ii) identification of immunologic differences and advantages of MN-based influenza vaccination compared to IM vaccination that will be used to improve the MN patch, (iii) production of MN patches for influenza vaccination under cGMP and IND approval from FDA, (iv) completion of a Phase I clinical trial assessing safety, tolerability, immunogenicity and acceptability of influenza vaccination using MN and (v) identification of regulatory, cost and policy issues to guide development and future introduction of our MN patch into clinical practice. These outcomes not only impact influenza vaccination, but also provide a basis for delivery of other vaccines and drugs using MN patches. PUBLIC HEALTH RELEVANCE: Despite annual influenza vaccination campaigns, CDC attributes 36,000 deaths and 226,000 hospitalizations per year in the US to influenza, with an associated cost of ~$100 billion per year. As a quantum advance, this project will develop a novel microneedle patch designed to increase vaccination coverage by enabling simple, self-vaccination and increase vaccine immunogenicity by targeting antigen delivery to skin. The proposed Phase I clinical trial will provide the first human study of this technology.

描述（由申请人提供）：流感是全世界发病和死亡的主要原因。尽管疫苗接种是预防感染最有效的策略，但流感疫苗接种覆盖率不足，需要提高疫苗的免疫原性。我们建议开发一种微针贴片，该贴片足够简单，可以通过自我给药来提高疫苗接种覆盖率，并且专门设计用于通过靶向皮肤中的树突状细胞来提高免疫原性。微针 (MN) 是微米级的实心针，可通过简单、无痛和微创的方法将疫苗直接注射到皮肤中。该贴片旨在实现皮肤疫苗接种，贴片应用时间仅需几秒钟，不会产生尖锐的生物危害废物，并且在无需冷藏的情况下储存期间抗原稳定。 这个具有里程碑意义的项目的目标是开发用于流感疫苗接种的 MN 贴片，并在 I 期临床试验中评估其安全性和免疫原性。在目标 1 中，我们将在佐治亚理工学院设计、配制和制造 MN，以实现简单、快速的应用和长期稳定性。在埃默里大学的目标 2 中，我们将在三种动物模型中评估 MN 疫苗接种，目的是验证人体试验的适用性并增强免疫原性。目标 3 将通过外部承包商和顾问来实现，以开发和验证 cGMP 生产、进行 GLP 临床前研究并获得 IND。这项工作将在埃默里大学希望诊所的目标 4 中进行 I 期临床试验，以评估使用 MN 贴片进行流感疫苗接种的安全性、耐受性、免疫原性和可接受性。最后，目标 5 将基于 PATH 评估与自我管理流感疫苗接种相关的监管、成本和政策问题。 这项研究的预期成果是 (i) 开发一种低成本的 MN 贴片，以简单、快速的方式接种流感疫苗，(ii) 确定基于 MN 的流感疫苗接种与 IM 疫苗接种相比的免疫学差异和优势，用于改进 MN 贴片，(iii) 根据 FDA 的 cGMP 和 IND 批准生产用于流感疫苗接种的 MN 贴片，(iv) 完成 I 期临床试验，评估使用 MN 进行流感疫苗接种的安全性、耐受性、免疫原性和可接受性，以及 (v) 确定监管、成本和政策问题，以指导我们的 MN 贴片的开发和未来将其引入临床实践。这些结果不仅影响流感疫苗接种，还为使用 MN 贴片提供其他疫苗和药物提供基础。 公共卫生相关性：尽管每年都会开展流感疫苗接种活动，但 CDC 将美国每年 36,000 例死亡和 226,000 例住院归因于流感，每年的相关成本约为 1000 亿美元。作为一项重大进展，该项目将开发一种新型微针贴片，旨在通过实现简单的自我疫苗接种来提高疫苗接种覆盖率，并通过将抗原递送到皮肤来提高疫苗的免疫原性。拟议的一期临床试验将提供该技术的首次人体研究。