An SEB Immunoprotectant

SEB 免疫保护剂

• 批准号: 8711005
• 负责人: Kevin John Whaley
• 金额: $ 100万
• 依托单位: MAPP BIOPHARMACEUTICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-10 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8711005
• 关键词: Aerosols; Antibodies; Bacteria; Biological Response Modifier Therapy; Biological Warfare; Breathing; Categories; Cessation of life; Chemistry; Cost Savings; Data; Development; Dose; Drug Formulations; Exhibits; Exposure to; FDA approved; Failure; Food Poisoning; Funding; Investigational Drugs; Investigational New Drug Application; Military Personnel; Monoclonal Antibodies; Mus; National Institute of Allergy and Infectious Disease; Nicotiana; Pharmaceutical Preparations; Pharmacology and Toxicology; Phase; Population; Prophylactic treatment; Route; Safety; Shock; Specificity; Staphylococcal Enterotoxin B; Testing; Therapeutic; Time; Toxic Shock Syndrome; Toxic effect; Toxin; United States National Institutes of Health; War; aerosolized; base; biodefense; body system; immunogenicity; meetings; nonhuman primate; prevent; public health relevance; research clinical testing; stability testing

DESCRIPTION (provided by applicant): Staphylococcal enterotoxin B (SEB; Category B agent), a toxin that commonly causes classic food poisoning and can cause a non-menstrual toxic shock syndrome (TSS), has been studied as 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. SEB exhibits severe toxicity by the inhalation route; once inhaled it causes widespread systemic damage, multi- organ system failure, and even shock and death at microgram doses. Clearly, 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 biologics that can potently neutralize toxins. Because of their stability, specificity, versatility, and low potential for immunogenicity, mAbs are ideal for biodefense-related countermeasures. As a result of successful completion of our Phase 1 efforts, we have identified a highly potent mAb that protects mice from systemic and aerosol challenge. Further, in this proposal we are combining forces with Integrated Biotherapeutics (Gaithersburg, MD) whose team has identified an additional anti-SEB mAb via separate NIAID funding. Together we will determine which of the two mAbs is the most appropriate for continued development, resulting in cost-savings for NIH. The Long Range Objective of this project is to develop a safe and effective immunoprotectant product for SEB. We expect the initial indication will be for pre- and post-exposure prophylaxis. The Specific Aims and Milestones of this proposal are: Aim 1. Produce the two candidate mAbs using a Nicotiana benthamiana based rapid antibody manufacturing platform (RAMP). Aim 2. Evaluate the pre- and post-exposure efficacy of the two mAbs in non-human primates against aerosolized SEB. The most efficacious mAb, to be designated MB-SEB, will be chosen for continued development. Aim 3. Complete Investigational New Drug (IND) enabling studies to prepare for clinical evaluation of MB-SEB in accordance with regulatory requirements. Using RAMP mAb produced under Good Manufacturing Practice (GMP), the studies necessary (pharmacology and toxicology; chemistry, manufacturing and control data) to submit an IND application will be performed to support a Phase 1 safety trial.

描述（由申请人提供）：葡萄球菌肠毒素B （SEB； B类制剂）是一种通常引起经典食物中毒并可引起非经期中毒性休克综合征（TSS）的毒素，已被研究为潜在的生物战制剂。重要的是，SEB来源于常见的容易接触的细菌，相对容易产生，并且可以以稳定的气溶胶形式输送。SEB通过吸入途径表现出严重的毒性；一旦吸入，它会引起广泛的全身损害，多器官系统衰竭，甚至在微克剂量下休克和死亡。显然，在战争时期，SEB的袭击对平民和战场都是毁灭性的。目前，没有针对SEB的预防或治疗方法。