Monoclonal Antibody SEB Immunoprotectant

说明(申请人提供)：葡萄球菌肠毒素B(SEB；B类制剂)是一种潜在的生物战剂，通常会引起经典食物中毒，并可导致非经期中毒性休克综合征(TSS)。重要的是，SEB来自常见的容易接触的细菌，相对容易生产，并可以以稳定的气雾剂形式提供。SEB攻击将对平民人口以及战争期间战场上的平民造成毁灭性的打击。目前，还没有针对SEB的预防或治疗方法。单抗是FDA批准的一类治疗药物，被证明可以中和毒素。由于其特异性、稳定性、高效性和通用性，人源单抗是生物防御相关对策的理想选择。这项NIAID-AT-SBIR建议的产品开发目标是：(1)产生一组完全人类的抗SEB单抗；(2)根据小鼠中毒模型的预防效果选择铅抗SEB单抗；(3)比较在哺乳动物细胞培养中表达的铅单抗与在快速、高度可扩展的制造系统中表达的相同单抗的保护效果。长期目标是开发一种安全有效的SEB免疫保护剂产品。设想了两种产品形式：1)一种预防性产品，由人抗SEB单抗组成，用于在可能暴露于武器化SEB之前肌肉注射。2)由人抗SEB单抗和S单抗联合使用的治疗产品，以提供暴露后的保护。针对这一应用的实验将在随后的第二阶段提案中执行。公共卫生相关性：葡萄球菌肠毒素B(SEB；B类制剂)是一种潜在的生物战剂，通常会引起经典食物中毒，并可导致非经期中毒性休克综合征(TSS)。重要的是，SEB来自常见的容易接触的细菌，相对容易生产，并可以以稳定的气雾剂形式提供。目前，还没有针对SEB的预防或治疗方法。Mapp生物制药公司的研发团队建议开发一种新型、安全、低成本的免疫保护剂，用于预防和治疗SEB中毒。

DESCRIPTION (provided by applicant): Staphylococcal enterotoxin B (SEB; Category B agent), a toxin that commonly causes classic food poisoning and can cause a nonmenstrual toxic shock syndrome (TSS), is a potential biological warfare agent. Importantly, SEB is derived from common readily accessible bacteria, is relatively easily produced, and can be delivered in a stable aerosol form. An SEB attack would be devastating to civilian populations as well as on the battlefield during times of war. Currently, there are no preventatives or therapeutics available against SEB. Monoclonal antibodies (Mabs) are a class of FDA-approved therapeutics shown to neutralize toxins. Because of their specificity, stability, high potency, and versatility human Mabs are ideal for biodefense related countermeasures. The Product Development Goals of this NIAID-AT-SBIR proposal are to: (1) generate a panel of fully human anti-SEB Mabs; (2) select lead anti-SEB Mabs based upon prophylactic efficacy in mouse intoxication models; (3) compare the protective efficacy of the lead Mabs when expressed in mammalian cell culture with the identical Mab expressed in a rapid, highly scalable manufacturing system. The Long Range Objective is to develop a safe and effective immunoprotectant product for SEB. Two product modalities are envisioned: 1) A preventive product consisting of a human anti-SEB Mab for intramuscular administration prior to potential exposure to weaponized SEB. 2) A therapeutic product consisting of the human anti-SEB Mabs administered in combination with Mab(s) against pro-inflammatory cytokines to provide protection post- exposure. Experiments addressing this application will be performed in a subsequent Phase 2 proposal. PUBLIC HEALTH RELEVANCE: Staphylococcal enterotoxin B (SEB; Category B agent), a toxin that commonly causes classic food poisoning and can cause a nonmenstrual toxic shock syndrome (TSS), is a potential biological warfare agent. Importantly, SEB is derived from common readily accessible bacteria, is relatively easily produced, and can be delivered in a stable aerosol form. Currently, there are no preventatives or therapeutics available against SEB. Mapp Biopharmaceutical's R&D team proposes to develop a novel, safe, low cost immunoprotectant for preventing and treating SEB intoxication.