PA22-176, SBIR, Phase I, Development of a SARS-CoV-2 emerging variant infectivity and immune evasion panel to quantify the efficacy of vaccine booster induced neutralizing antibodies.

PA22-176，SBIR，第一阶段，开发 SARS-CoV-2 新兴变异感染性和免疫逃避小组，以量化疫苗增强剂诱导的中和抗体的功效。

• 批准号: 10699562
• 负责人: Brian Hetrick
• 金额: $ 27.32万
• 依托单位: VIRONGY BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2024-06-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10699562
• 关键词: PA22; 176; SBIR; Phase; Development

Summary As the COVID19 pandemic and vaccine deployment continue there is an urgent need to monitor emerging variants for their infectivity and ability to escape both prior infection and vaccine induced neutralizing antibodies. Currently, there is no way to rapidly quantify emerging variants infectivity and immune evading capacity. The standard for quantifying viral infectivity involves the use of harvested viral isolates and performing quantitative plaque assays, which are tedious and time consuming. Additionally, the use of infectious SARS-CoV-2 requires high-level containment in BSL-3 facilities that limits its application in common clinical and research laboratories. Pseudoviruses have been widely used to model SARS-CoV-2 infectivity and antibody neutralization. Pseudoviruses, such as those derived from lentivirus and vesicular stomatitis virus, can mimic the entry process of SARS-CoV-2. However, these pseudovirions consist of mostly non-coronavirus structural proteins and require 2-3 days to generate results. Recently, a novel hybrid alphavirus-SARS-CoV-2 pseudovirion (HA-CoV-2) has been developed by the P.I. (Hetrick) for rapid (3-6 hours) and accurate quantification of viral infectivity and sensitivity to neutralizing antibodies. The HA-CoV-2 particle is a non-replicating SARS-CoV-2 virus-like particle (VLP) composed of only SARS-CoV-2 structural proteins (S, M, N, and E) and a RNA reporter genome derived from a fast expressing alphavirus vector. Our preliminary studies have demonstrated that the HA-CoV-2 assay can rapidly quantify the differences in neutralizing antibodies from vaccinated and previously infected individuals to specific SARS-CoV-2 variants. Virongy has recently licensed the HA-CoV-2 technology from George Mason University, and plans to develop commercial kits with panels of HA-CoV-2 particles that represent the SARS- CoV-2 variants currently in circulation with the greatest infectivity and potential for immune escape. As viral variants continue to emerge there is an urgent need to monitor the infectivity and evaluate the effectiveness of the vaccines on emerging variants. The HA-CoV-2 system would provide a robust platform for rapid and accurate quantification of viral variant infectivity and the neutralizing antibody response. We propose to develop a HA- CoV-2 pseudovirus-based panel to examine infectivity and neutralizing antibody response with two specific aims. Specific Aim 1 is to screen the 50 most prevalent SARS-CoV-2 variant spike proteins in circulation and identify the emerging variants with the highest infectivity using the HA-CoV-2 pseudovirus platform. Specific aim 2 is to conduct antibody neutralization assays of each COVID variant in circulation and determine the sensitivity of each variant to both vaccine and infection induced anti-serum and convalescent plasma. For this study the WHO International Standard and Reference Panel for anti-SARS-CoV-2 antibody will be screened along with a standard recombinant RBD antibody. Following the initial screening the top 5 variants will be selected to develop a commercial panel kit for vaccine and booster developers to evaluate the efficacy of their prophylactics. As part of this screening process Virongy plans to collaborate with John Hopkins university and other non-profit public health organizations to provide all the data acquired in this study. The HA-CoV-2 pseudovirus are currently marketed on Virongy’s company website (virongy.com) for research use only.

概括 随着COVID19大流行和疫苗部署的继续，迫切需要监视新兴 其感染的变体以及逃脱先前感染和疫苗诱导中和抗体的能力。 当前，无法快速量化新兴变体感染和免疫逃避能力。这 量化病毒感染的标准涉及使用收获的病毒分离株并进行定量 斑块阿萨斯（Assas），乏味且耗时。此外，使用感染性SARS-COV-2需要 在BSL-3设施中，高级遏制限制了其在常见临床和研究实验室中的应用。 假病毒已被广泛用于模拟SARS-COV-2感染和抗体神经元化。 假病毒，例如源自病毒病毒和囊泡性气孔病毒的假病毒，可以模仿进入过程 SARS-COV-2。但是，这些伪造委员会主要由非核纳病毒结构蛋白组成，需要 2-3天生成结果。最近，一种新型的混合α-SARS-COV-2伪病毒（HA-COV-2）具有 由P.I.开发（Hetrick）快速（3-6小时），并准确地定量病毒感染和 对中和抗体的敏感性。 HA-COV-2粒子是一种非复制的SARS-COV-2病毒样粒子 （VLP）仅由SARS-COV-2结构蛋白（S，M，N和E）和RNA报告基因组得出 来自快速表达的α病毒载体。我们的初步研究表明HA-COV-2分析 可以快速量化来自接种疫苗和先前感染的个体中和抗体的差异 特定的SARS-COV-2变体。 Virongy最近从乔治·梅森（George Mason）获得了HA-COV-2技术许可 大学，并计划使用代表SARS的HA-COV-2颗粒面板开发商业套件。 COV-2的变体目前流通，具有最大的感染和免疫逃生的潜力。作为病毒 变体继续出现，迫切需要监测感染并评估 新兴变体的疫苗。 HA-COV-2系统将为快速准确提供强大的平台 定量病毒变异感染和中和抗体反应。我们建议开发一个 基于COV-2伪病毒的面板以两个特定的目的检查感染和中和抗体反应。 具体目的1是筛选50个最普遍的SARS-COV-2变体峰值蛋白，并识别 使用HA-COV-2伪病毒平台具有最高感染的新兴变体。具体目标2是 在循环中对每种共证变量进行抗体神经化评估，并确定 疫苗和感染的每种变体都会诱导抗血清和康复等离子体。在这项研究中 抗SARS-COV-2抗体的国际标准和参考面板将与 标准重组RBD抗体。初始筛选后，将选择前5个变体以开发 用于疫苗和增强开发人员的商业面板套件，以评估其预防效率。作为一部分 在此筛选过程中，Virongy计划与John Hopkins大学和其他非营利性公众合作 卫生组织提供本研究中获得的所有数据。 HA-COV-2伪病毒目前是 在Virongy公司网站（Virongy.com）上销售，仅用于研究用途。