Transcutaneous Immunization for an Anthrax Vaccine

炭疽疫苗的经皮免疫

• 批准号: 6789136
• 负责人: GREGORY M GLENN
• 金额: $ 100万
• 依托单位: IOMAI CORPORATION
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6789136
• 关键词: Bacillus anthracis; Langerhans' cell; active immunization; anthrax; anthrax vaccines; bacterial antigens; bioterrorism /chemical warfare; drug delivery systems; enterotoxins; immunity; immunomodulators; immunopharmacology; laboratory mouse; laboratory rabbit; pharmacokinetics; topical drug application; transdermal drug delivery; vaccine development; vaccine evaluation; vector vaccine

DESCRIPTION (provided by applicant): Vaccination plays a central role in a biodefense strategy and is the established intervention against anthrax. Further development of both existing and new biodefense vaccines is required to improve the anthrax vaccine acceptability and better tailor the means of delivery to make the utilization of the vaccine in mass immunization campaigns more feasible. 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 II SBIR proposal will focus on the development of a dry self-adhesive anthrax 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 anthrax vaccine in adhesive blends containing both LT and rPA; to characterize the in vitro release and recovery of rPA and LT from formulated dry patches; to screen antigen release, delivery and adjuvanticity by assessing the systemic immune responses elicited by LT/rPA adhesive patches; to test the functionality of antigen released form LT/rPA adhesive patches in rabbit challenge models; to assess the stability of rPA and LT in dry adhesive patch formulations; to develop a pilot scale (lot size >1,000 patches) manufacturing process for cGMP production of rPNLT patches that could support clinical trials. These activities will prepare the groundwork for clinical evaluation of an anthrax patch in a parallel clinical development program, funded outside of this Phase II SBIR. The development of a formulated, manufacturable dry adhesive patch anthrax vaccine that is simple to apply and has strong patient acceptance will significantly advance the transcutaneous immunization technology and lead to broadening of this promising approach to vaccination.

描述（由申请人提供）：疫苗接种在生物防御战略中起着核心作用，是针对炭疽的既定干预措施。 需要进一步开发现有的和新的生物防御疫苗，以提高炭疽疫苗的可接受性，并更好地调整接种手段，使疫苗在大规模免疫接种活动中的使用更加可行。经皮免疫是一种新的无针和无装置免疫方法，使用贴片来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，导致安全和有效的全身免疫应答。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背景下的免疫应答。SBIR第二阶段的建议将侧重于开发一种干的自粘性炭疽疫苗贴片，这种贴片可以生产（cGMP），并可在临床上实际应用。干燥的粘性贴片已被证明在临床环境中有效且安全地递送LT。该提案的具体目的是评估LT与炭疽疫苗一起配制在含有LT和rPA的粘合剂混合物中时的生物活性和效力;表征rPA和LT从配制的干贴剂中的体外释放和回收;通过评估LT/rPA粘合剂贴剂引起的全身免疫应答来筛选抗原释放、递送和佐剂性;在家兔激发模型中测试从LT/rPA粘合剂贴剂释放的抗原的功能性;评估干燥粘合剂贴剂制剂中rPA和LT的稳定性;开发可支持临床试验的rPNLT贴剂cGMP生产的中试规模（批量> 1，000片贴剂）生产工艺。这些活动将为在本II期SBIR之外资助的平行临床开发项目中对炭疽贴剂进行临床评价奠定基础。开发一种配制的、可制造的、易于施用且具有很强的患者接受性的干粘性贴剂炭疽疫苗将显著推进经皮免疫技术，并导致这种有希望的接种方法的拓宽。