title: A physico-chemical assessment of the thermal stability of pneumococcal conjugate vaccine components.
abstract: Physico-chemical analysis of pneumococcal polysaccharide (PS)-protein conjugate vaccine components used for two commercially licensed vaccines was performed to compare the serotype- and carrier protein-specific stabilities of these vaccines. Nineteen different monovalent pneumococcal conjugates from commercial vaccines utilizing CRM197, diphtheria toxoid (DT), Protein D (PD) or tetanus toxoid (TT) as carrier proteins were incubated at temperatures up to 56°C for up to eight weeks or were subjected to freeze-thawing (F/T). Structural stability was evaluated by monitoring their size, integrity and carrier protein conformation. The molecular size of the vaccine components was well maintained for Protein D, TT and DT conjugates at -20°C, 4°C and F/T, and for CRM197 conjugates at 4°C and F/T. It was observed that four of the eight serotypes of Protein D conjugates tended to form high molecular weight complexes at 37°C or above. The other conjugated carrier proteins also appeared to form oligomers or 'aggregates' at elevated temperatures, but rarely when frozen and thawed. There was evidence of degradation in some of the conjugates as evidenced by the formation of lower molecular weight materials which correlated with measured free saccharide. In conclusion, pneumococcal-Protein D/TT/DT and most CRM197 bulk conjugate vaccines were stable when stored at 2-8°C, the recommended temperature. In common between the conjugates produced by the two manufacturers, serotypes 1, 5, and 19F were relatively less stable and 6B was the most stable, with types 7F and 23F also showing good stability.
authors.affiliation: a Division of Bacteriology ; National Institute for Biological Standards and Control ; Hertfordshire , UK.
authors.forename: Fang
authors.initials: F
authors.lastname: Gao
authors.forename: Kay
authors.initials: K
authors.lastname: Lockyer
authors.forename: Karena
authors.initials: K
authors.lastname: Burkin
authors.forename: Dennis T
authors.initials: DT
authors.lastname: Crane
authors.forename: Barbara
authors.initials: B
authors.lastname: Bolgiano
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry*; D055598:Chemical Phenomena; D004355:Drug Stability; D006801:Humans; D022242:Pneumococcal Vaccines / Q000737:chemistry*; D055550:Protein Stability; D013696:Temperature; D018074:Vaccines, Conjugate / Q000737:chemistry
chemical_list: D002352:Carrier Proteins; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate
keywords: CRM197, Cross-Reacting Material- 197; DT, diphtheria toxoid; F/T, freeze-thawing, HPAEC-PAD, high pH anion-exchange chromatography with pulsed amperometric detection; HPAEC-PAD; HPLC; MW, molecular weight; PD, Protein D; PS, polysaccharide; Pn, pneumococcal; Protein D; SEC, size-exclusion chromatography; Streptococcus pneumoniae; TT, tetanus toxoid; conjugate vaccine; fluorescence spectroscopy; pneumococcal; polysaccharide; stability