Hydroxypropyl-ß-Cyclodextrin Preserves the Potency of Adenovirus Vectors Under Heat/Light Stress.

Adenoviral vectors represent one of the most studied vector systems currently available for use in gene therapy and/or vaccine applications. However, their long-term storage stability is a challenge to overcome for biopharmaceuticals. The selection of appropriate excipients to protect these biologics during development and final formulation is critical in ensuring product stability against various physical stresses throughout its shelf life.
Formulations of our model Adv5-CMV-Cre-GFP virus vector containing 5% hydroxypropyl-ß-cyclodextrin (HPBCD) were able to maintain a significantly higher 50% tissue culture infectious dose (TCID50) under heat (i.e., 25 °C, 40 °C) and light (i.e., white light + UV) stresses. At 25 °C, the presence of 5% HPBCD allowed for a 10-fold higher retention in potency vs. those without. At 40 °C, HPBCD-formulated Adv5 samples maintained their ability to infect above the detection threshold 20-50% (i.e., 2-6 weeks) longer than their counterparts. Lastly, our study also showed that 5% HPBCD conferred complete protection when Adv5 vectors were subjected to either white or UV light stress. When subjected to a combination of white + UV light stress, both 5% HPBCD and 0.02% polysorbate 80 provided improved protection compared to the control buffer.
This study has demonstrated the effective use of HPBCD in the stabilization of Adenovirus vectors, suggesting the function of cyclodextrins in extending the shelf life of the vaccine/gene therapy delivery vehicle and, potentially, other similar systems.