(582an) Stabilization of a Fiberless Adenovirus Gene Vector

The ubiquitous nature of the coxsackie adenovirus receptor (CAR) and undesirable interactions between cell surface proteins and the adenovirus fiber and capsid proteins lead to a vector that has both limited and promiscuous tropism. Fiberless adenovirus, however, has the potential to reduce the promiscuous tropism commonly associated with adenoviral-based gene vectors but removal of the fiber protein has been shown to negatively affect the virus stability. To identify the most stable conditions for formulation and storage, we explored the effects of pH and temperature on stability of the virus particle. Our results indicated that the stability of fiberless adenovirus was significantly increased when the virus was kept in mildly acidic conditions, around pH 6. Further, the stability of fiberless adenovirus could be improved by including excipients. The results from screening a library of GRAS excipients showed that non-ionic surfactants and amino acids tended to increase the thermal transition temperature of the virus particle, and more importantly, improved biological activity after prolonged thermal stress. In conclusion, our data demonstrated that instability of fiberless adenovirus could be ameliorated by carefully controlling the pH and stabilizing excipients, thereby leading the way to development of gene vectors or vaccines based on fiberless adenovirus.