POLYMERS FOR AUGMENTING R BOTULINUM VACCINE EFFICACY

描述（改编自申请人摘要）：肉毒杆菌中毒是一种 由梭菌神经毒素引起的神经肌肉中毒。 人类是 通过食物接触肉毒梭菌产生的神经毒素 中毒伤口肉毒杆菌中毒和细菌定植感染的发生率 新生儿肉毒杆菌中毒是罕见的。 虽然感染 微生物可以用抗生素治疗，不存在特异性 肉毒杆菌毒素的药物治疗类毒素，如福尔马林灭活的 疫苗，可制备用于以下个体的主动免疫： 可能接触到C。植物或其毒素。 但问题 与这种免疫有关的问题，包括需要 单剂量昂贵的多价类毒素，以及对 类毒素向毒素的逆转需要单剂量 用安全的疫苗进行免疫。 重组体的最新可用性 片段C肉毒杆菌（r-FCBt）疫苗和可吸收凝胶形成 运营商有理由推行拟议的计划。 的目标 第一阶段是确定使用可吸收凝胶形成的可行性 和微球聚酯载体在开发r-FCBt疫苗中的应用 用于鼻内和皮下免疫。 第一阶段需要（1） 制备和表征聚合物载体;（2）配制和 在小鼠中评价使用E型的候选控释系统， 和F r-FCBt疫苗;（3）确定抗体应答;和（4） 用个别同源血清型进行攻击研究。 第一阶段的结果将用于设计第二阶段的计划，包括（1） 研究所有r-FCBt疫苗的免疫和保护（A，B，C， D、E、F和G）对最高剂量的同源和可能的 异源毒素血清型;（2）开发、放大和评估 多价r-FCBt疫苗;以及（3）进行简短的安全性研究 在多价疫苗上。 拟议商业应用：不可用

DESCRIPTION (Adapted from the applicant's abstract): Botulism is a neuromuscular poisoning caused by clostridial neurotoxins. Humans are exposed to neurotoxins produced by Clostridial botulinum through food poisoning. Incidences of wound botulism and a colonizing infection of neonates known as infant botulism are rare. Although the infective microorganism can be treated by antibiotics, there exists no specific drug therapy for botulinum toxins. Toxoids, as in formalin-inactivated vaccines, can be prepared for active immunization of individuals who are likely to be exposed to C. Botulinum or its toxins. However, problems associated with such immunization, including the need for more than a single dose of expensive, multivalent toxoids, and concerns about reversion of the toxoids to toxins created a need for single-dose immunization with a safe vaccine. Recent availability of recombinant fragment C botulinum (r-FCBt) vaccine and absorbable gel-forming carriers justified pursuing the proposed program. The objective of Phase I is to determine the feasibility of using absorbable gel-forming and micro-spherical polyester carriers in developing a r-FCBt vaccine for intranasal and subcutaneous immunization. Phase I entails (1) preparing and characterizing the polymeric carriers; (2) formulating and evaluating, in mice, candidate controlled release systems using Type E and F r-FCBt vaccines; (3) determining the antibody response; and (4) conducting challenge studies with individual homologous serotypes. Phase I results will be used to design Phase II plans that include (1) studying immunization and protection of all r-FCBt vaccines (A, B, C, D, E, F, and G) against highest dose of homologous and possibly heterologous toxin serotypes; (2) developing, scaling-up, and evaluating a multivalent r-FCBt vaccine; and (3) conducting a brief safety study on the multivalent vaccine. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE