Transcutaneous Immunization for an Anthrax Vaccine

炭疽疫苗的经皮免疫

• 批准号: 6878534
• 负责人: GREGORY M GLENN
• 金额: $ 98.58万
• 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/6878534
• 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.

说明(申请人提供)：疫苗接种在生物防御战略中发挥核心作用，是对炭疽病的既定干预措施。需要进一步开发现有和新的生物防御疫苗，以提高炭疽疫苗的可接受性，并更好地定制递送手段，使疫苗在大规模免疫活动中的使用更加可行。经皮免疫是一种利用贴片递送疫苗抗原和有效佐剂的无针无装置免疫的新方法。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。这项第二阶段的SBIR提案将专注于开发一种干燥的自粘性炭疽疫苗贴片，该贴片可以制造(CGMP)，并可在临床上实际应用。干燥、粘合的贴片已被证明在临床环境中可以有效和安全地提供LT。这项建议的具体目的是评估LT与炭疽疫苗在含有LT和RPA的粘合剂中配制时的生物活性和效力；表征配制的干贴剂中RPA和LT的体外释放和回收；通过评估LT/RPA粘贴剂引起的系统免疫反应来筛选抗原的释放、递送和佐剂；在兔攻击模型中测试LT/RPA粘贴剂释放的抗原的功能性；评估RPA和LT在干胶贴剂制剂中的稳定性；开发中试规模(批量和1,000个贴片)生产cGMP的rPNLT贴片，以支持临床试验。这些活动将为在一个平行的临床开发计划中对炭疽贴片进行临床评估奠定基础，该计划是在该第二阶段SBIR之外资助的。开发一种配方、可制造的干粘性斑贴炭疽疫苗，这种疫苗应用简单，患者接受度高，将极大地促进经皮免疫技术的发展，并导致这一有希望的疫苗接种方法的扩大。