Influenza vaccination using a microneedle patch

描述(申请人提供)：流感是全球发病率和死亡率的主要原因。虽然接种疫苗是预防感染的最有效策略，但流感疫苗接种覆盖面不够，需要提高疫苗的免疫原性。我们建议开发一种微针贴片，这种贴片足够简单，可以通过自我给药来增加疫苗接种覆盖率，并专门设计通过靶向皮肤中的树突状细胞来提高免疫原性。微针(MN)是一种微米级的实心针，通过一种简单、无痛和微创的方法将疫苗直接注入皮肤。该贴片旨在实现皮肤疫苗接种，贴片应用时间仅需数秒，不会产生尖锐的生物危险废物，并且在无需冷藏的情况下储存期间抗原稳定。这个里程碑式的项目的目标是开发一种用于流感疫苗接种的MN贴片，并在一期临床试验中评估其安全性和免疫原性。在目标1中，我们将以佐治亚理工学院为基础，设计、配制和制造MN，以实现简单、快速的应用和长期稳定。在埃默里大学的目标2中，我们将评估MN疫苗在三种动物模型中的接种情况，目的是验证是否适合人体试验并提高免疫原性。目标3将与外部承包商和顾问一起实现，以开发和验证cGMP制造，进行GLP临床前研究，并获得IND。这项工作将在埃默里希望诊所的目标4中进行的第一阶段临床试验中达到高潮，以评估使用MN贴片接种流感疫苗的安全性、耐受性、免疫原性和可接受性。最后，Aim 5将以Path为基础，评估与自行接种流感疫苗相关的监管、成本和政策问题。这项研究的预期结果是：(I)开发一种以简单、快速的方式管理流感疫苗的低成本MN贴片，(Ii)确定MN流感疫苗接种与IM接种的免疫学差异和优势，将用于改进MN贴片，(Iii)在cGMP和FDA的IND批准下生产用于流感疫苗接种的MN贴片，(Iv)完成第一阶段临床试验，评估使用MN接种流感疫苗的安全性、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贴片的开发和未来进入临床实践。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了基础。

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.