SampleStream: A Radically Simplified Platform for Protein Sample Preparation

摘要：全球SARS-CoV-2大流行的兴起暴露了我们在应对新事物方面的严重弱点 病原体。改进的三个主要领域包括疫苗、疗法和 血清学。所有这三个领域都需要准确评估个人免疫反应的工具。 疫苗的开发需要批次到批次的质量控制，并需要抗体测试来确定是否有 特殊的配方已经在患者体内诱导了抗体的产生。同样，对抗体的深入了解 在有轻微疾病的人群中创造的可以为生物制剂提供有价值的潜在候选产品，这些产品可以迅速 制作。最后，个体体内针对病原体的抗体的特性和数量可以指示 无论一个人是否被感染，重要的是，他们是否具有持久的免疫力。 集成蛋白质技术公司开发了一种名为SampleStream的技术，可以实现快速纯化和 在交付给质谱仪之前，浓缩大的蛋白质，如抗体。在此，我们建议使用 这项技术将免疫沉淀与质谱学相结合。使用Thermo的翠鸟FLEX平台 Fisher，96份血清样本可以用包被重组Spike蛋白的磁珠同时处理 来自SARS-CoV-2。由此产生的样本将包含针对病毒的个人抗体。质量 对这些抗体的光谱分析将提供序列和丰度信息。当与患者结合时 结果数据，这将使IPT能够识别在更广泛的人群中真正中和的抗体集。 最终，这些抗体可以作为药物先导，通过确保有效的免疫来帮助疫苗的开发。 产生响应，并使全球范围内的感染/免疫监测和评估成为可能。 IPT的技术和我们的“插件”系统使我们能够以独特的方式快速集成这些平台和SampleStream 提供与质谱仪的高通量接口。我们有机会对……产生重大影响 这场危机和模板的新技术，将使更快的反应未来的病原体。

Abstract: The rise of the global SARS-CoV-2 pandemic has exposed serious weaknesses in our ability to respond to novel pathogens. Three major areas of improvement include the rapid development of vaccines, therapeutics, and serosurveillence. All three of these areas require tools that accurately assess the immune response across individuals. Vaccine development requires lot-to-lot quality control and requires an antibody test that establishes whether or not a particular formulation has elicited antibody creation in the patient. Likewise, intimate knowledge of the antibodies created in populations with mild disease can provide valuable potential candidates for biologics that can be rapidly produced. Finally, the identity and amount of antibodies specific to a pathogen within an individual can indicate whether or not an individual has been infected, and, importantly, whether or not they have lasting immunity. Integrated Protein Technologies has developed a technology called SampleStream that enables rapid purification and concentration of large proteins, such as antibodies, prior to delivery to mass spectrometry. Herein, we propose using this technology to couple immunoprecipitation to mass spectrometry. Using the KingFisher flex platform from Thermo Fisher, 96 serum samples can be processed simultaneously with magnetic beads coated with recombinant spike protein from SARS-CoV-2. The resultant samples will contain the antibodies specific to the virus on a per-individual basis. Mass spectral analysis of these antibodies will provide sequence and abundance information. When combined with patient outcome data, this will enable IPT to identify the set of antibodies that are truly neutralizing in the broader population. Ultimately, these antibodies can serve as drug leads, can aid in vaccine development by ensuring a potent immune response is generated, and enable surveillance and assessment of infection/immunity across the globe. IPT’s technology and our “plugin” system enable us to rapidly integrate these platforms and SampleStream uniquely provides the high throughput interface with mass spectrometry. We have an opportunity to have a significant impact on this crisis and template a new technology that will enable more rapid responses to future pathogens.