STTR Phase I: A platform for the rapid discovery of human antibodies as therapeutics for infectious disease (COVID-19)

这项小企业技术转让（STTR）第一阶段项目的更广泛影响是建立一个针对传染病的新型快速药物发现平台。一个机会是挖掘尚未开发的人类抗体的多样性，并将其开发成治疗方法。该技术旨在快速识别候选药物并选择治疗候选药物。建立的平台将准备应对新出现的疫情和现有的顽固病原体，如耐药细菌。优先考虑的是当前的COVID-19大流行，但这可以扩展到其他潜在的病原体。这个STTR一期项目将建立一个对抗传染病的人类抗体疗法的新发现平台。破坏性的新病原体，如SARS-CoV-2 （COVID-19）和耐抗生素细菌的增加，要求采取替代和快速的治疗方法。传统的治疗性抗体开发通常涉及动物模型或/和亲和选择系统。它们昂贵且耗时，需要多个步骤，包括人性化，以减轻免疫中和。该方法仅在9天内识别针对感兴趣病原体的人抗体（IgG）。这种方法还利用了人类抗体尚未开发的多样性。该管道首先收集含有浆母细胞的供体细胞，对其进行修饰以捕获自身分泌的IgG，从而使相关细胞富集。细胞在单孔中以高通量方式分类。该过程继续进行高通量克隆，抗体表达，以及初步的结合和中和筛选。从细胞到最初的结合筛选需要9天的时间，识别出数百种不同特征的抗体。初始筛选之后是进一步的结合动力学测试和中和试验。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impacts of this Small Business Technology Transfer (STTR) Phase I project are to establish a novel and rapid drug-discovery platform aimed at infectious diseases. An opportunity is to tap into an unexplored diversity of human antibodies and develop them into therapies. This technology aims to identify drug candidates and select therapeutic candidates quickly. The established platform will be poised to counter emerging outbreaks and existing stubborn pathogen such as drug-resistant bacteria. The priority is the current COVID-19 pandemic, but this can be expanded to other potential pathogens. This STTR Phase I project will establish a novel discovery platform of human antibody therapeutics to counter infectious diseases. The rise of devastating new pathogens, such as SARS-CoV-2 (COVID-19) and antibiotic-resistant bacteria, calls for alternative and rapid therapeutic approaches. Traditional therapeutic antibody development generally involves animal models or/and affinity selection systems. They are expensive and lengthy, requiring multiple steps, including humanization, to mitigate immune neutralization. The proposed method identifies human antibodies (IgG) targeting a pathogen of interest in only nine days. The approach also capitalizes on an unexplored diversity of human antibodies. The pipeline begins with a collection of donor cells containing plasmablasts, which are modified to capture own-secreted IgG allowing for the enrichment of the relevant cells. The cells are sorted in single wells in a high throughput fashion. The process continues with high throughput cloning, antibody expression, and a preliminary binding and neutralization screen. The pipeline lasts nine days from cells to the initial binding screen, identifying hundreds of antibodies of varying characteristics. The initial screen is followed by further tests of binding kinetics and neutralization assays.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.