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: 10733320
• 负责人: Kathryn Kosuda
• 金额: $ 84.54万
• 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/10733320
• 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; 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; Measures; Modeling; Mutation; Needles; Outcome; Perception; Performance; Persons; Phase; Phase I Clinical Trials; Population; Positioning Attribute; Preclinical Testing; Preparation; Process; Production; Protocols documentation; Public Health; Qualifying; Quality Control; Recommendation; Recording of previous events; Risk; Seasons; Silk; Site; Skin; Source; Specific qualifier value; System; T cell response; T-Lymphocyte; Technology; Testing; Therapeutic; Time; Translations; Vaccine Antigen; Vaccines; Vendor; Virus; Work; World Health Organization; anti-influenza; burden of illness; clinical lot; clinical translation; combat; commercialization; design; design verification; flu; implementation design; improved; influenza infection; influenza virus vaccine; influenzavirus; manufacture; manufacturing facility; manufacturing process; meetings; operation; phase 1 designs; pre-Investigational New Drug meeting; pre-clinical; preclinical study; prevent; product development; response; seasonal influenza; technology platform; 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.

项目总结/摘要 世界卫生组织估计，每年流感导致300万至500万人严重患病。 全球死亡人数高达65万。虽然有预防流感感染的季节性疫苗， 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， 每年重新配制疫苗。因此，季节性疫苗的公共卫生效益受到以下因素的阻碍： 疗效差（2017-18赛季估计为36%）。这一挑战突出表明，迫切需要改进 流感疫苗，以促进体液反应（发病，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 抗原，以模拟自然感染动力学超过2周，导致更大的多样性， 抗体和改善的T细胞反应。这是通过使用丝素蛋白生物材料在微针中完成的 阵列形式，可以容易地施用到皮肤。在短暂的5分钟佩戴时间后， 尖端从贴片释放并植入真皮内。这些丝尖被设计用来稳定 疫苗抗原在体温下释放，同时在2周内缓慢释放抗原有效载荷。在动物 比较常规注射与我们的持续释放方法的研究，我们证明了4倍 保护性T细胞增加，抗体滴度增加5倍， 致命的挑战贴剂给药在皮肤病模型（无毛豚鼠）中也耐受良好 和约克郡猪）。在这些临床前概念验证结果的基础上，我们提出的目标是 目前的工作是通过实施一项 质量管理体系、装置设计的优化和定型、GMP的建立 生产和其他CMC相关活动，以及监管参与，以确保符合FDA 要求.完成这些目标后，Vaxess将提交IND并开始1期 我们的基因芯片贴片用于广泛保护性季节性流感的商业化途径的临床研究 疫苗接种，MIMIX流感。