title: Characterization of Propylene Glycol-Mitigated Freeze/Thaw Agglomeration of a Frozen Liquid nOMV Vaccine Formulation by Static Light Scattering and Micro-Flow Imaging.
abstract: The purpose of this work was to investigate the susceptibility of an aluminum adjuvant and an aluminum-adjuvanted native outer membrane vesicle (nOMV) vaccine formulation to freeze/thaw-induced agglomeration using static light scattering and micro-flow Imaging analysis; and to evaluate the use of propylene glycol as a vaccine formulation excipient by which freeze/thaw-induced agglomeration of a nOMV vaccine formulation could be mitigated. Our results indicate that including 7% v/v propylene glycol in an nOMV containing aluminum adjuvanted vaccine formulation, mitigates freeze/thaw-induced agglomeration.
  
  
  
  We evaluated the effect of freeze-thawing on an aluminum adjuvant and an aluminum adjuvanted native outer membrane vesicle (nOMV) vaccine formulation. Specifically, we characterized the freeze/thaw-induced agglomeration through the use of static light scattering, micro-flow imaging, and cryo-electron microscopy analysis. Further, we evaluated the use of 0-9% v/v propylene glycol as an excipient which could be included in the formulation for the purpose of mitigating the agglomeration induced by freeze/thaw. The results indicate that using 7% v/v propylene glycol as a formulation excipient is effective at mitigating agglomeration of the nOMV vaccine formulation, otherwise induced by freeze-thawing.
authors.affiliation: Merck & Co., West Point, PA christopher.mensch@merck.com.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Mensch
authors.affiliation: Merck & Co., West Point, PA.
authors.forename: Harrison B
authors.initials: HB
authors.lastname: Davis
authors.affiliation: Merck & Co., West Point, PA.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Blue
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry; D000536:Aluminum Hydroxide / Q000737:chemistry; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001702:Biopharmaceutics / Q000379:methods*; D020285:Cryoelectron Microscopy; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005615:Freezing; D008027:Light; D022401:Meningococcal Vaccines / Q000737:chemistry*; D046210:Microfluidic Analytical Techniques; D009345:Neisseria meningitidis / Q000276:immunology*; D010316:Particle Size; D010710:Phosphates / Q000737:chemistry; D019946:Propylene Glycol / Q000737:chemistry*; D066329:Protein Aggregates; D012542:Scattering, Radiation; D013056:Spectrophotometry, Ultraviolet; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D001425:Bacterial Outer Membrane Proteins; D005079:Excipients; D022401:Meningococcal Vaccines; D010710:Phosphates; D066329:Protein Aggregates; D000536:Aluminum Hydroxide; C069096:aluminum hydroxyphosphate; D019946:Propylene Glycol
keywords: Agglomeration; Aluminum adjuvant; Cryo-EM; Formulation; Freeze/thaw; Micro-flow imaging; Particle sizing; Propylene glycol; Static light scattering; Vaccine; nOMV