Process Analytical Technology for Recombinant Pandemic Flu Vaccines: Viral Ultrastructure, Aggregation, and Binding

Here we describe our progress to develop 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.  ES-DMA has the potential to fulfill this need.  Here we describe our efforts 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 determination of stoichiometry and vaccine efficacy.