Transcutaneous Immunization for an Anthrax Vaccine

描述（由申请人提供）：疫苗接种在生物防御策略中起着核心作用，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，并更好地定制递送手段，使疫苗在大规模免疫运动中的利用更加可行。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。该II期SBIR提案将侧重于开发一种干燥的自粘炭疽疫苗贴片，该贴片可生产（cGMP）并可实际应用于临床。在临床环境中，干燥的粘接贴片已被证明可以有效和安全地输送肝移植。本建议的具体目的是评估在含有LT和rPA的粘合剂混合物中与炭疽疫苗配制时LT的生物活性和效力；表征配制干贴剂中rPA和LT的体外释放和恢复；通过评估LT/rPA贴片引发的全身免疫反应，筛选抗原释放、传递和佐剂性；在家兔攻毒模型中检测LT/rPA贴片释放抗原的功能；评估rPA和LT在干胶贴片配方中的稳定性；开发可支持临床试验的rPNLT贴片cGMP生产的中试规模（批量为1000片）生产工艺。这些活动将为在该II期SBIR之外资助的平行临床开发项目中对炭疽贴片进行临床评估奠定基础。开发一种配制的、可制造的、操作简单且患者接受度高的干粘贴剂炭疽疫苗，将大大推进经皮免疫技术，并扩大这种有前途的疫苗接种方法。

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.