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

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 andgt; $280M by 2023.Public Health Relevance Statement Influenza affects from 5 to 20 percent of the U.S. population each year. Recombinant hemagglutinin influenza vaccine is promising for its efficacy and unique ability to respond rapidly to pandemics; however, lack of a high- affinity purification technology presents a major challenge for its commercial scale implementation. The goal of this SBIR Phase I project is to develop a hemagglutinin-specific affinity membrane chromatography product for the rapid and improved purification of recombinant hemagglutinin influenza vaccine.