Quality control of polyvalent pneumococcal polysaccharide-protein conjugate vaccine by nephelometry.
A nephelometric method was used for quantitative analysis of individual polysaccharides (PSs) in a polyvalent pneumococcal conjugate vaccine using CRM(197) as carrier protein. Using this method, the individual types 4, 6B, 9V, 14, 18C, 19F and 23F PSs were found to range between 82.3 to 119% of the manufacturer's indicated values. During conjugation using reductive amination, pneumococcal PS was first oxidized to introduce aldehyde groups. Higher or lower levels of antigen-antibody reaction were observed in periodate activated and then reduced PS of some serotypes compared to non-treated PS. Use of oxidized and reduced PS may provide an early indication of change in conjugation process. Furthermore, since the final monovalent and polyvalent conjugate vaccines gradually change during the storage period, the nephelometry provides an useful analytical method for stability study of these vaccines.
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, U.S.A.
Chi Jen
CJ
Lee
D000907:Antibodies, Bacterial / Q000032:analysis; D001894:Borohydrides / Q000378:metabolism; D002240:Carbohydrate Sequence; D004305:Dose-Response Relationship, Drug; D008027:Light; D008969:Molecular Sequence Data; D009391:Nephelometry and Turbidimetry / Q000379:methods; D010100:Oxygen / Q000378:metabolism; D010504:Periodic Acid / Q000378:metabolism; D022242:Pneumococcal Vaccines / Q000737:chemistry*; D011135:Polysaccharides, Bacterial / Q000032:analysis*; D011485:Protein Binding; D012542:Scattering, Radiation
D000907:Antibodies, Bacterial; D001894:Borohydrides; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D010504:Periodic Acid; C009288:metaperiodate; D010100:Oxygen