SBIR Phase I: Hemagglutinin-specific affinity capture membrane for rapid purification of influenza vaccines

项目摘要 该SBIR第一阶段项目将开发一种新型亲和膜，以解决关键的纯化挑战， 生产高纯度和有效的重组血凝素（rHA）流感疫苗。在美国，每个 每年有5%到20%的人患上流感。在世界范围内，大约有3到5个 严重病例每年高达500，000例，死亡人数每年高达500，000例。血凝素（HA）是血凝素中的主要蛋白质。 流感疫苗负责产生免疫反应。由于其生产时间短（例如， 与基于细胞的疫苗和基于蛋的疫苗（例如3至6个月）相比，rHA疫苗显示 迅速应对大流行性流感毒株的巨大希望。然而，缺乏高亲和力 rHA的纯化技术。目前，耗时且多个低亲和力下游纯化 步骤用于获得足够的纯度用于商业生产。SBIR第一阶段项目的目标是 证明开发用于快速、选择性纯化的高容量亲和膜的可行性 的HA。从这一创新中衍生出来的产品将是市场上第一个一次性膜色谱 可以通过提供增加的免疫原性来简化和改进重组疫苗纯化过程的柱。 亲和性、纯度和回收率优于常规方法。I期研究的目的是（1）证明 合成HA亲和膜的可行性和（2）测试原型膜色谱 用于捕获纯化重组HA疫苗的色谱柱，并将其性能与现有的 技术.在具体目标1中，我们将评估合成条件和结合和修饰所起的作用。 缓冲液条件对性能的影响。在具体目标2中，Purilogics将 与Sciogen，LLC的研究人员合作，量化和基准性能， 由Sciogen从细胞上清液制备的重组HA疫苗。多次迭代的合成和 性能表征将改善膜性能。在第二阶段，Purilogics计划（i）建立 一个可扩展的过程，以生产原型进行全面的性能测试，确定灭菌 协议，产品保质期和可重复使用性;（ii）与潜在的工业合作伙伴进行实地研究 客户;和（iii）测试基于受体的纯化可以提高疫苗有效性的假设 通过动物研究。新色谱柱产品的市场准入将是销售给纯化科学家， 生物制药公司的工程师。预计预包装、一次性 Purilogics正在开发的HA亲和色谱柱预计到2023年将超过2.8亿美元。

Project Summary This SBIR Phase I project will develop a novel affinity membrane to address key purification challenges for producing highly pure and effective recombinant hemagglutinin (rHA) influenza vaccines. In the U.S. each year, from 5 to 20 percent of the population becomes ill with influenza. Worldwide, there are about 3 to 5 million severe cases and up to 500,000 deaths yearly. Hemagglutinin (HA) is the primary protein in the influenza vaccines responsible for producing an immune response. Due to its short production time (e.g. one month) compared to that of cell-based and egg based-vaccines (e.g. three to six months), rHA vaccines show great promise to rapidly respond to pandemic influenza strains. However, there is a lack of a high-affinity purification technology for rHAs. Currently, time consuming and multiple low-affinity downstream purification steps are used to obtain sufficient purity for commercial manufacturing. The goal of this SBIR Phase I project is to demonstrate the feasibility of developing high-capacity affinity membranes for the rapid, selective purification of HA. Products derived from this innovation will be first-in-market, disposable membrane chromatography columns that can simplify and improve the recombinant vaccine purification process by offering increased affinity, purity, and recovery over conventional methods. The aims of the Phase I study are (1) to demonstrate the feasibility of synthesizing HA affinity membranes and (2) to test prototype membrane chromatography columns for capture purification of recombinant HA vaccines and benchmark their performance against existing technology. In Specific Aim 1, we will evaluate the roles played by synthesis conditions and bind-and-elute buffer conditions on performance using high-throughput experiments. In Specific Aim 2, Purilogics will collaborate with researchers at Sciogen, LLC to quantify and benchmark performance for purification of recombinant HA vaccines prepared by Sciogen from cell supernatant. Multiple iterations of synthesis and performance characterization will improve membrane performance. In Phase II, Purilogics plans to (i) establish a scalable process to produce prototypes for comprehensive performance testing, determining sterilization protocols, product shelf life, and reusability; (ii) conduct field research with industrial partners who are potential customers; and (iii) test the hypothesis that the receptor-based purification can improve vaccine effectiveness through animal studies. Market entry for the new column products will be sales to purification scientists and engineers in biopharmaceutical companies. The estimated total addressable market for prepacked, disposable HA affinity chromatography columns under development by Purilogics is expected to be > $280M by 2023.