NASAL ANTHRAX VACCINE DELIVERY FORMULATIONS

描述（由申请人提供）：2001年美国发生的炭疽紧急事件促使公共卫生当局考虑，如果面临生物恐怖主义事件，他们如何开展大规模免疫运动。目前在美国使用的炭疽疫苗需要在18个月内进行6次皮下注射，加上每年一次的加强注射。我们建议开发一种新的，鼻腔给药，延长释放的炭疽疫苗用于初级或加强免疫。我们的炭疽抗原鼻腔配方将有几个重要的优势：它将(1)允许简单，无创给药；(2)提高免疫应答，减少注射次数；(3)具有生物黏附性，具有较长的停留时间，因为制剂将能够粘附在鼻子的后部，在那里粘膜纤毛活性导致更快的药物清除，从而提高疫苗的生物利用度；(4)增加抗原递送，增强抗原稳定性，起到抗原储存库或贮存库的作用；(5)消除了明矾作为佐剂的需要。建议的制剂将是基于聚合物的两组分制剂，将在给药前在手持给药装置中混合。（该输送装置不在本项目范围内，尽管此类装置已用于其他疫苗）。该研究将涉及具有药物配方、疫苗生物学和免疫学专业知识的研究人员的合作研究。长期目标是一种快速、易于施用、缓释的炭疽疫苗。

DESCRIPTION (provided by applicant): The 2001 anthrax emergency in the United States has prompted public health authorities to consider how they might conduct mass immunization campaigns if confronted by a bioterrorism event. The anthrax vaccine now used in the United States requires six subcutaneous injections over an 18-month period, plus yearly boosters. We propose to develop a new, nasally administered, extended-release anthrax vaccine for use as primary or booster immunizations. Our nasal formulation for anthrax antigen will have several important advantages: it will (1) allow easy, non-invasive administration; (2) improve the immune response and reduce the number of shots; (3) be bioadhesive, with a longer residence time because the formulation will be able to adhere to the posterior portion of the nose, where mucociliary activity results in faster clearance of medications and thus increases the bioavailability of the vaccine; (4) increase antigen delivery, enhance antigen stability, and act as an antigen reservoir or depot; and (5) eliminate the need for alum as an adjuvant. The proposed formulation will be a polymer-based, two-part formulation that will be mixed in a hand-held delivery device just prior to administration. (The delivery device is beyond the scope of this project, although such devices have already been used for other vaccines). The study will involve collaborative studies by investigators with expertise in pharmaceutical formulation, vaccine biology, and immunology. The long-term goal is a fast-acting, easily administered, extended-release anthrax vaccine.