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

这一小企业技术转让第一阶段项目的更广泛影响是建立一个针对传染病的新的快速药物发现平台。一个机会是利用未知的人类抗体多样性，并将它们开发成治疗方法。这项技术旨在快速识别候选药物和选择治疗候选药物。建立的平台将准备应对新爆发的疫情和现有的顽固病原体，如耐药细菌。当务之急是当前的新冠肺炎大流行，但这可以扩大到其他潜在病原体。这一STTR第一期项目将建立一个新的人类抗体疗法的发现平台，以对抗传染病。毁灭性新病原体的崛起，如新冠肺炎(SARS-CoV-2)和抗药性细菌，要求采用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。它们既昂贵又耗时，需要包括人性化在内的多个步骤来缓解免疫中和。建议的方法只需9天就能识别出针对感兴趣病原体的人类抗体(IgG)。该方法还利用了未知的人类抗体多样性。这条管道从一组含有浆母细胞的供体细胞开始，这些浆细胞经过改造以捕获自身分泌的免疫球蛋白，从而使相关细胞得以浓缩。这些单元以高吞吐量的方式被分选在单井中。这一过程继续进行高通量克隆、抗体表达和初步结合和中和筛选。从细胞到最初的结合筛选，这条管道持续了9天，识别了数百种不同特征的抗体。最初的筛选之后是结合动力学和中和分析的进一步测试。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.