Process analytical technology for recombinant pandemic flu vaccines: Viral ultrastructure, aggregation, and binding

Here we describe our progress in developing electrospray differential mobility analysis (ES-DMA) into a process analytical technology (PAT) for recombinant vaccines. The threat of pandemic flu (e.g. avian influenza H5N1, swine flu H1N1, etc.) remains a significant public concern. Recombinantly produced vaccines hold significant advantages over traditional means of growing vaccines including increased production rates, shorter times between viral identification and clinical treatment, and improved safety profiles. However, accelerated production methods also require advanced process control sensors (i.e. process analytical technologies) that can rapidly and accurately detect out-of-specification intermediates. ESDMA has the potential to fulfill this need. Here we describe our efforts to use ES-DMA to (1) rapidly quantify the assembly state and integrity of recombinantly produced virus like particles (VLPs), (2) determine the viral aggregation state, and (3) quantify antibody-virus binding necessary to evaluate stoichiometry and vaccine efficacy.