Hepatitis B Surface Antigen Particle Purification by Immunoaffinity Chromatography Based on CDI-CB.Hep-1 mAb Monolithic Supports

by Rodolfo Valdés, Urh Černigoj, Eduardo Sánchez, Daily Hernández, Blass Nemec, Miladys Limonta, Miguel Castillo, Bárbara Pérez, Urška Vidic, Jana Vidič, Mirjan Žorž, Andrés Tamayo, Leonardo Gómez, Williams Ferro, Yurisley Aldama, Nika Lendero Krajnc, Daniela Marc, and Aleš Štrancar
Volume 17, Open Access (June 2018)


Bead matrices have been used in affinity chromatography to purify molecules in multiple applications. For instance, the hepatitis B surface antigen (HBsAg) is one of the molecules purified by this technique for human vaccine development programs. However, the use of monolithic supports have emerged as the advantageous choice for affinity chromatography based on convective mass transfer, a high number of channels, and low backpressures at high flow rates. For this reason, several experiments were conducted to determine the suitability of CB.Hep-1 monoclonal antibody (mAb) immunosorbent developed on carboxyimidazole (CDI)-monolithic supports (ligand concentrations: 0.5, 1.0, and 7.0 mg/mL) for HBsAg particle purification. Key results from this study show the highest amounts of HBsAg adsorbed (3059.31 ± 865.71 µg HBsAg/mL immunosorbent, n = 2), and HBsAg eluted (2884.50 ± 541.01 µg HBsAg/mL immunosorbent, n = 2), were estimated in the 1.0 mg/mL-CDI-CB. Hep-1 mAb monolithic support immunosorbents. In addition, the ligand leakage was always < 3 ng mAb/µg HBsAg (approved limit) in the 1.0 mg/ mL-CDI-CB.Hep-1 mAb immunosorbents. Experiments also evidenced the high purity and molecular homogeneity of purified HBsAg particles (< 95 %) across 20 purification cycles. Therefore, the ligand concentration could be reduced up to 1.0 mg/mL, which would enable a notable decrease in the mAb amount required for vaccine manufacturing, as compared to bead matrices (4.0 mg/mL). This study demonstrated that CDI-CB.Hep-1 mAb monolithic support immunosorbents are best suited for assessing the large-scale purification performance of HBsAg particles for human vaccine development programs at low ligand concentration and high flow rates…

Citation:
Valdes R et al. Hepatitis B surface antigen particle purification by immunoaffinity chromatography based on CDI-CB.Hep-1 mAb monolithic supports. BioProcess J, 2018; 17. https://doi.org/10.12665/J17OA.Valdes

Posted online June 5, 2018.