Formulated Patch for Topical Influenza Vaccine

描述(由申请人提供)：经皮免疫是一种新的无针头和无设备免疫方法，使用贴片递送疫苗抗原和有效佐剂。局部皮肤免疫利用皮肤的免疫生物学原理，产生安全有效的全身免疫反应。佐剂LT的使用已被证明在临床前和临床环境中都能安全地增强皮肤的免疫反应。这一阶段的SBIR提案将重点开发一种干燥的自粘性流感疫苗贴片，该贴片可以生产(CGMP)，并可在临床上实际应用。干燥的粘合剂贴片已被证明在临床环境中有效和安全地提供LT。这项建议的具体目的是评估LT与流感疫苗在含有LT和三价裂解病毒疫苗的粘合剂中配制时的生物活性和效力；表征流感疫苗和LT从配制的干燥贴片中的体外释放和回收情况；表征临床前研究中局部注射流感疫苗与肌肉注射引起的免疫反应的比较；开发可支持临床试验的cGMP生产流感/LT贴片的中试规模(1,000个贴片)生产工艺。这些活动将为流感贴片的临床评估做好准备。目前，美国平均一个流感季节每年与2500万至3000万流感病例、15万人住院和2万至4万人死亡有关。儿童的感染率最高，但最严重的疾病和与流感相关的死亡发生在65岁的老年人中。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。灭活流感疫苗的效力取决于接受者的年龄和免疫能力，以及病毒与每个季节流通的疫苗之间的相似程度。众所周知，老年人在免疫后往往不会形成Hal抗体的保护性水平。在皮肤环境中安全使用强效佐剂可能会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。无针头也可能有助于将流感贴片的使用扩展到儿童人群，在这些人群中，流感免疫接种现在是ACIP推荐的，也将是该开发计划的后续目标。

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.