title: Stabilizing effects of excipients on dissociation of intact (146S) foot-and-mouth disease virions into 12S particles during storage as oil-emulsion vaccine.
abstract: Most conventional foot-and-mouth disease virus (FMDV) vaccines contain oil-adjuvant. Their potency decreases upon prolonged storage. Intact (146S) FMDV particles can dissociate into 12S degradation products with a concomitant decrease in immunogenicity. We therefore measured virion stability in vaccines using two previously developed ELISAs to separately quantify 12S and 146S particles. Virions completely dissociated into 12S particles within 3 months after oil-emulsification. Dissociation occurred at a much lower rate in a comparable aqueous solution that was not oil-emulsified. Thus, oil-emulsification stimulates virion dissociation, presumably due to the protein denaturing effect of the oil-water interface. In real-time stability studies the stability of oil-adjuvanted virions of four different FMDV strains was significantly increased by addition of sucrose and BSA in a synergistic manner. Contrary to BSA addition, the effect of sucrose addition was concentration dependent. This study illustrates the importance of analysing antigen integrity after oil-emulsification and provides methods for FMDV vaccine stabilization.
authors.affiliation: Central Veterinary Institute of Wageningen UR, P.O. Box 65, 8200 AB Lelystad, The Netherlands. Electronic address: Michiel.Harmsen@wur.nl.
authors.forename: M M
authors.initials: MM
authors.lastname: Harmsen
authors.affiliation: Central Veterinary Institute of Wageningen UR, P.O. Box 65, 8200 AB Lelystad, The Netherlands.
authors.forename: H P D
authors.initials: HP
authors.lastname: Fijten
authors.affiliation: Central Veterinary Institute of Wageningen UR, P.O. Box 65, 8200 AB Lelystad, The Netherlands.
authors.forename: D F
authors.initials: DF
authors.lastname: Westra
authors.affiliation: Central Veterinary Institute of Wageningen UR, P.O. Box 65, 8200 AB Lelystad, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Dekker
mesh_terms: D000818:Animals; D004355:Drug Stability; D004356:Drug Storage; D004655:Emulsions; D004797:Enzyme-Linked Immunosorbent Assay; D005079:Excipients; D005536:Foot-and-Mouth Disease / Q000517:prevention & control; D029544:Foot-and-Mouth Disease Virus / Q000648:ultrastructure*; D012710:Serum Albumin, Bovine; D013395:Sucrose; D013997:Time Factors; D014765:Viral Vaccines / Q000737:chemistry*; D014771:Virion / Q000648:ultrastructure*
chemical_list: D004655:Emulsions; D005079:Excipients; D014765:Viral Vaccines; D012710:Serum Albumin, Bovine; D013395:Sucrose
keywords: Adjuvant; Excipients; Foot-and-mouth disease; Oil emulsion; Vaccine stability; Viral integrity