Formulated Patch for Topical Influenza Vaccine

局部流感疫苗配方贴剂

• 批准号: 6788454
• 负责人: GREGORY M GLENN
• 金额: $ 47.26万
• 依托单位: IOMAI CORPORATION
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-15 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6788454
• 关键词: SDS polyacrylamide gel electrophoresis; bioengineering /biomedical engineering; biomaterial development /preparation; biomaterial interface interaction; biotechnology; dosage forms; enterotoxins; enzyme linked immunosorbent assay; immune response; immunomodulators; influenza vaccines; laboratory mouse; pharmacokinetics; transdermal drug delivery; vaccine development; vaccine evaluation

DESCRIPTION (provided by applicant): Transcutaneous immunization is a new approach to needle-free and device-free immunization using a patch to deliver vaccine antigens and potent adjuvants. Topical skin immunization takes advantage of the immunobiology of the skin leading to safe and effective systemic immune responses. The use of the adjuvant LT has been shown to safely augment the immune response in the context of the skin in both preclinical and clinical settings. This phase I SBIR proposal will focus on the development of a dry self-adhesive flu vaccine patch, which can be manufactured (cGMP) and is practical to apply in the clinic. A dry adhesive patch has been shown to effectively and safely deliver LT in clinical settings. The specific aims of this proposal are to assess the biological activity and potency of LT when formulated with the flu vaccine in adhesive blends containing both LT and trivalent split virus vaccine; to characterize the in vitro release and recovery of influenza vaccine and LT from formulated dried patches; to characterize the systemic and pulmonary mucosal immune responses elicited by topical administered influenza vaccine compared to immune responses elicited by intramuscular injection in preclinical studies; to develop a pilot scale (lot size >1,000 patches) manufacturing process for cGMP production of influenza/LT patches that could support clinical trials. These activities will prepare the groundwork for clinical evaluation of an influenza patch. An average influenza season in the United States is currently associated with 25-30 million flu cases, 150,000 hospitalizations and 20,000 to 40,000 deaths each year. Rates of infection are highest among children, but the most serious illness and influenza related deaths are among the elderly = or >=65 years. Approximately 60% of flu-related hospitalizations occur among the elderly and greater than 90% of flu related deaths are elderly. The effectiveness of inactivated influenza vaccine is dependant upon the age and immune competence of the recipient and the degree of similarity between the viruses and the vaccine in circulation each season. It is well established that the elderly often do not develop protective level of HAl antibodies post-immunization. The safe use of potent adjuvants in the context of the skin may address the relative immune deficit in the elderly and this may be the first target of future clinical evaluation. Needle-free may also aid in the extension of use of a flu patch into the pediatric population where influenza immunization is now recommended by the ACIP and will be a subsequent goal of this development program.

描述（由申请人提供）：经皮免疫是一种使用贴片递送疫苗抗原和强效佐剂的无针和无器械免疫的新方法。局部皮肤免疫利用皮肤的免疫生物学，导致安全有效的全身免疫反应。在临床前和临床环境中，佐剂LT的使用已被证明可以安全地增强皮肤的免疫反应。第一阶段SBIR提案将侧重于开发一种干式自粘流感疫苗贴片，该贴片可制造（cGMP），并可在临床应用。在临床环境中，干胶粘贴已被证明可以有效和安全地递送肝移植。本建议的具体目的是评估LT与流感疫苗在含有LT和三价分裂病毒疫苗的粘合剂混合物中配制时的生物活性和效力；描述流感疫苗和LT从配制的干燥贴剂中的体外释放和回收；在临床前研究中，与肌肉注射流感疫苗引起的免疫反应相比，局部注射流感疫苗引起的全身和肺粘膜免疫反应的特征；开发可支持临床试验的流感/LT贴片cGMP生产的中试规模（批量为1000个贴片）生产工艺。这些活动将为流感贴片的临床评价奠定基础。目前，美国平均每年流感季节有2500万至3000万流感病例，15万人住院治疗，2万至4万人死亡。儿童的感染率最高，但最严重的疾病和与流感有关的死亡发生在老年人中。大约60%的流感相关住院病例发生在老年人中，90%以上的流感相关死亡病例是老年人。灭活流感疫苗的有效性取决于接种者的年龄和免疫能力，以及每个季节流行的病毒与疫苗之间的相似程度。老年人免疫后通常不会产生保护性水平的HAl抗体。在皮肤环境下安全使用强效佐剂可以解决老年人的相对免疫缺陷，这可能是未来临床评估的第一个目标。无针也有助于将流感贴片的使用扩展到儿科人群中，目前ACIP建议儿童接种流感疫苗，这将是该开发项目的后续目标。