The focus of the Process Development group is to develop upstream and downstream processes to support the Antigen Discovery Unit of the Texas Children's Hospital Center for Vaccine Development. These programs include protein vaccines for hookworm (Na-GST-1, Na-APR-1), Chagas disease (Tc24, TSA-1), SARS (RBD protein), and Leishmaniasis (LdNH-36). After basic R&D has been performed and potential vaccine antigens are identified by in-vitro and in-vivo testing, the goal of the Process Development group is to optimize the expression of the target antigen to maximize protein yield (Upstream development) and to develop purification processes (Downstream development) to maximize recovery and purity of the target antigen in order to support advanced investigations of the target molecules.
To achieve these goals initial small-scale experiments are performed to 1) identify media, feeds and culture conditions to optimize production of the target molecules, and 2) buffer conditions, resins, and capture/chromatographic steps to obtain target molecule in high purity and stability. When a basic production and purification process is developed for the antigen of interest, the process is scaled up to 10-20L to achieve a true manufacturing process. Once the scaled up process has been established, reproducibility runs are performed to investigate the robustness and repeatability of the manufacturing process in order to establish overall expected protein yields to support third-party cGMP manufacture for clinical trial production.
The Process Development Unit has approximately 450 square feet of dedicated space, plus shared space in Texas Children's Hospital Center for Vaccine Development including a fermentation room equipped with two BioFlo 3000 and one CelliGen® 310 benchtop fermentors and a BioFlo 4500 Steam in Place Fermentor.
Fermentation space is currently being expanded to support three Sartorius B-CDU II fermentors. Fermentation equipment has from 5L to 25L. The laboratory is also equipped with Akta Explorer and Akta Purifier chromatography systems as well as two Acta Avant chromatography systems running Unicorn software for downstream purification.