Monoclonal Antibody SEB Immunoprotectant

描述（由申请方提供）：葡萄球菌肠毒素B（SE B; B类制剂）是一种通常引起典型食物中毒并可引起非月经中毒性休克综合征（TSS）的毒素，是一种潜在的生物战剂。重要的是，SEB来源于常见的容易获得的细菌，相对容易产生，并且可以以稳定的气溶胶形式递送。SEB的袭击将对平民以及战争时期的战场造成毁灭性影响。目前，没有针对SEB的预防或治疗药物。单克隆抗体（Mab）是一类FDA批准的治疗药物，可中和毒素。由于其特异性、稳定性、高效力和多功能性，人单克隆抗体是生物防御相关对策的理想选择。该NIAID-AT-SBIR提案的产品开发目标是：（1）生成一组全人源抗SEB单抗;（2）基于小鼠中毒模型中的预防效力选择先导抗SEB单抗;（3）比较在哺乳动物细胞培养物中表达的先导单抗与在快速、高度可扩展的生产系统中表达的相同单抗的保护效力。长期目标是开发安全有效的SEB免疫保护剂产品。设想了两种产品形式：1）预防性产品，其由人抗SEB Mab组成，用于在潜在暴露于武器化SEB之前肌内施用。2)一种治疗产品，由人抗SEB单抗与抗促炎性细胞因子的单抗联合给药组成，以提供暴露后保护。解决该应用的实验将在随后的第2阶段提案中进行。公共卫生相关性：葡萄球菌肠毒素B（SE B; B类制剂）是一种常见的引起典型食物中毒的毒素，可引起非月经期中毒性休克综合征（TSS），是一种潜在的生物战剂。重要的是，SEB来源于常见的容易获得的细菌，相对容易产生，并且可以以稳定的气溶胶形式递送。目前，没有针对SEB的预防或治疗药物。Mapp生物制药的研发团队提出开发一种新型、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.