Microarray Patch for Broadly Protective Seasonal Influenza Vaccination

用于广泛保护性季节性流感疫苗的微阵列贴片

• 批准号: 10570001
• 负责人: Kathryn Kosuda
• 金额: $ 100万
• 依托单位: VAXESS TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-09 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10570001
• 关键词: Address; Age-Months; Animal Model; Animals; Antibodies; Antibody titer measurement; Antigens; Biochemical; Biocompatible Materials; Biological; Biological Assay; Body Temperature; Cavia; Cellular Immunity; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinical; Clinical Research; Clinical Trials; Custom; Cyclic GMP; Dermatologic; Dermis; Device Designs; Devices; Dose; Engineering; Ensure; Equipment; Family suidae; Fibroins; Funding; Goals; Health Benefit; Hospitalization; Human; Immune response; Immunization; Implant; Individual; Infection; Influenza; Influenza vaccination; Injections; Kinetics; Maintenance; Manuals; Manufacturer Name; Measures; Modeling; Mutation; Outcome; Perception; Performance; Persons; Phase; Phase I Clinical Trials; Population; Positioning Attribute; Preclinical Testing; Preparation; Process; Production; Protocols documentation; Public Health; Quality Control; Recording of previous events; Risk; Seasons; Silk; Site; Skin; Source; System; T cell response; T-Lymphocyte; Technology; Testing; Therapeutic; Time; Translations; Vaccine Antigen; Vaccines; Vendor; Virus; Work; World Health Organization; anti-influenza; base; burden of illness; clinical lot; clinical translation; combat; commercialization; design; design verification; flu; implementation design; improved; influenza infection; influenza virus vaccine; influenzavirus; manufacturing facility; manufacturing process; meetings; operation; phase 1 designs; pre-clinical; preclinical study; prevent; product development; response; seasonal influenza; universal vaccine; usability; vaccine delivery; vaccine efficacy

Project Summary/Abstract The World Health Organization estimates that each year influenza causes serious illness in 3 to 5 million people and up to 650,000 deaths globally. While seasonal vaccines to prevent influenza infection are available, frequent mutations in the virus require manufacturers to guess which strains will circulate each season and reformulate the vaccine annually. As a result, the public health benefit of seasonal vaccines is hampered by poor efficacy (estimated at 36% for the 2017-18 season). This challenge highlights the critical need to improve influenza vaccines to boost humoral responses (onset, magnitude, and breadth) and generate additional cellular immunity. Our technology focuses on engineering the sustained release of seasonal influenza vaccine antigen to mimic natural infection kinetics over 2 weeks, resulting in greater diversity of anti-influenza antibodies and improved T cell responses. This is accomplished using silk fibroin biomaterial in a microneedle array format that can be easily administered to the skin. After a brief 5 minute wear time, the silk microneedle tips are released from the patch and implanted within the dermis. These silk tips are engineered to stabilize vaccine antigens at body temperature while slowly releasing the antigen payload over 2 weeks. In animal studies comparing conventional injection to our sustained release approach, we demonstrated a 4-fold increase in protective T-cells, a 5-fold increase in antibody titers, and significantly higher survival following lethal challenge. Patch administration was also well tolerated in dermatological models (hairless guinea pigs and yorkshire swine). Building upon these preclinical proof-of-concept results, the objective of our proposed work is to prepare for clinical translation and commercialization of this technology through implementation of a Quality Management System, optimization and finalization of device design, establishment of GMP manufacturing and other CMC-related activities, and regulatory engagement to ensure compliance with FDA requirements. Having completed these aims, Vaxess will be positioned to file an IND and begin a Phase 1 clinical study on a path to commercialization of our microarray patch for broadly protective seasonal influenza vaccination, MIMIX-Flu.

项目摘要/摘要 世界卫生组织估计，每年有300万至500万人因流感而患上重病 全球人口和多达65万人死亡。虽然有预防流感感染的季节性疫苗可用， 病毒的频繁变异要求制造商猜测每个季节会传播哪些毒株，以及 每年重新配制疫苗。因此，季节性疫苗对公众健康的益处受到以下因素的阻碍 效果不佳(2017-18赛季估计为36%)。这一挑战突显了改进的迫切需要 流感疫苗可增强体液反应(发作、幅度和广度)，并产生额外的 细胞免疫。我们的技术专注于设计季节性流感疫苗的持续释放 模拟自然感染动力学的抗原，超过2周，导致更多的多样性的抗流感 抗体和改善的T细胞反应。这是使用丝素生物材料在微针中完成的 数组格式，可以轻松地管理到皮肤。在短短5分钟的佩戴时间后，丝绸微针 尖端从贴片中释放出来，植入真皮内。这些丝绸尖端经过精心设计，以稳定 疫苗抗原保持在体温，同时在2周内缓慢释放抗原有效载荷。在动物身上 研究比较了常规注射和我们的缓释方法，我们展示了4倍的 保护性T细胞增加，抗体效价增加5倍，并显著提高以下患者的存活率 致命的挑战。贴片给药在皮肤病模型(无毛豚鼠)中也有很好的耐受性 和约克郡猪)。基于这些临床前概念验证结果，我们建议的目标是 工作是通过实施一项 质量管理体系、设备设计的优化和定型、GMP的建立 制造和其他与CMC相关的活动，以及确保遵守FDA的监管参与 要求。在完成这些目标后，Vaxess将准备提交IND并开始第一阶段 广保护性季节性流感微阵列贴片商业化途径的临床研究 接种疫苗，MIMIX-流感。