title: Carbohydrate-based ice recrystallization inhibitors increase infectivity and thermostability of viral vectors.
abstract: The inability of vaccines to retain sufficient thermostability has been an obstacle to global vaccination programs. To address this major limitation, we utilized carbohydrate-based ice recrystallization inhibitors (IRIs) to eliminate the cold chain and stabilize the potency of Vaccinia virus (VV), Vesicular Stomatitis virus (VSV) and Herpes virus-1 (HSV-1). The impact of these IRIs was tested on the potency of the viral vectors using a plaque forming unit assay following room temperature storage, cryopreservation with successive freeze-thaw cycles and lyophilization. Viral potency after storage with all three conditions demonstrated that N-octyl-gluconamide (NOGlc) recovered the infectivity of shelf stored VV, 5.6 Log₁₀ PFU mL(-1) during 40 days, and HSV-1, 2.7 Log₁₀ PFU mL(-1) during 9 days. Carbon-linked antifreeze glycoprotein analogue ornithine-glycine-glycine-galactose (OGG-Gal) increases the recovery of VV and VSV more than 1 Log₁₀ PFU mL(-1) after 10 freeze-thaw cycles. In VSV, cryostorage with OGG-Gal maintains high infectivity and reduces temperature-induced aggregation of viral particles by 2 times that of the control. In total, OGG-Gal and NOGlc preserve virus potency during cryostorage. Remarkably, NOGlc has potential to eliminate the cold chain and permit room temperature storage of viral vectors.
authors: Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
authors: Shahrokh M
authors: SM
authors: Ghobadloo
authors: Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
authors: Anna K
authors: AK
authors: Balcerzak
authors: Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
authors: Ana
authors: A
authors: Gargaun
authors: Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
authors: Darija
authors: D
authors: Muharemagic
authors: Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
authors: Gleb G
authors: GG
authors: Mironov
authors: Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
authors: Chantelle J
authors: CJ
authors: Capicciotti
authors: Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
authors: Jennie G
authors: JG
authors: Briard
authors: Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
authors: Robert N
authors: RN
authors: Ben
authors: Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
authors: Maxim V
authors: MV
authors: Berezovski
mesh_terms: D021301:Antifreeze Proteins / Q000737:chemistry*; D002478:Cells, Cultured; D015925:Cryopreservation; D003451:Cryoprotective Agents / Q000737:chemistry; D003460:Crystallization; D005612:Freeze Drying; D006020:Glycopeptides / Q000737:chemistry; D018259:Herpesvirus 1, Human; D006801:Humans; D050296:Microbial Viability; D058425:Vaccines, Virus-Like Particle; D014616:Vaccinia virus; D018116:Vesiculovirus
chemical_list: D021301:Antifreeze Proteins; D003451:Cryoprotective Agents; D006020:Glycopeptides; D058425:Vaccines, Virus-Like Particle