J Pharm Sci. 2018 Jun 5. pii: S0022-3549(18)30327-7. DOI: 10.1016/j.xphs.2018.05.022 [Epub ahead of print]
VM Toprani, Y Cheng, N Wahome, H Khasa, LA Kueltzo, RM Schwartz, CR Middaugh, SB Joshi, DB Volkin
The zoonotic equine encephalitis viruses (EEV) can cause debilitating and life-threatening disease, leading to ongoing vaccine development efforts for an effective virus-like particle (VLP) vaccine based on three strains of EEV (Eastern, Western and Venezuelan or EEE, WEE and VEE VLPs, respectively). In this work, TEM and light scattering studies showed enveloped, spherical, and ∼70 nm sized VLPs. Biophysical studies demonstrated optimal VLP physical stability in the pH range of 7.5-8.5 and at temperatures below ∼50oC. Interestingly, the individual stability profiles differed notably between the three VLPs. Numerous pharmaceutical excipients were screened for their VLP stabilizing effects against thermal stress. Sucrose, sorbitol, sodium chloride and pluronic F-68 were identified as promising stabilizers and the concentrations and combinations of these additives were optimized. Candidate monovalent VLP bulk formulations were incubated at temperatures ranging from -80oC to 40oC to establish freeze-thaw, long-term (2-8°C) and accelerated stability trends. Good VLP stability was observed at each storage temperature, except for a distinct instability observed at -20°C. The interaction of monovalent and trivalent VLP formulations with aluminum adjuvants was examined, both in terms of antigen adsorption and desorption over time. The implications of these findings on future vaccine formulation development of EEV VLPs are discussed.