Quality control of pneumococcal conjugate vaccines

肺炎球菌结合疫苗的质量控制

• 批准号: 6543565
• 负责人: CHI-JEN LEE
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6543565
• 关键词: Streptococcus pneumoniae vaccine; antigen antibody reaction; bacterial polysaccharides; bacterial proteins; chemical conjugate; chemical stability; drug quality /standard; immunologic substance development /preparation; immunotherapy; intermolecular interaction; nephelometry; oxidation reduction reaction; transport proteins; trypsin; vaccine development

Summary: Pneumococcal PSs have been covalently linked to carrier proteins by the reductive amination. In this method, the PSs were oxidized by periodate to introduce aldehyde groups. The degree of periodate oxidation is an important first step in the conjugation process. Thus, immunochemical characterization of periodate activated PSs can provide useful information for control tests of pneumococcal conjugate vaccines. The objective of the present study was quantitative analysis of the PS content in the monovalent and 7-valent pneumococcal conjugate vaccines using Light scattering rate nephelometry. The antibody binding reactions to periodate activated and then reduced PS were also examined, appling rate nephelometry for quantitative determination of PS content. 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. Treatment of the conjugates with trypsin at 37 C resulted in increased PS content measurements for some types, including types 4 and 14. In addition, higher or lower levels of antigen-antibody reaction were introduced in periodate activated and then reduced PS for some serotypes compared to non-treated PS. Use of oxidized and reduced PS could provide an early indication of change in antigen-antibody binding and conjugate stability.

摘要：肺炎链球菌PSS已通过还原氨化作用与载体蛋白共价连接。在该方法中，PSS用高碘酸氧化来引入醛基团。高碘酸氧化程度是偶联过程中重要的第一步。因此，高碘酸盐激活的PSS的免疫化学特征可以为肺炎球菌结合疫苗的对照试验提供有用的信息。本研究的目的是用光散射率散射比浊法定量分析单价和七价肺炎球菌结合疫苗中PS的含量。用速率散射比浊法定量测定PS的含量，并检测抗体与高碘酸盐的结合反应。使用这种方法，4、6B、9V、14、18C、19F和23F型PSS的范围在制造商指示值的82.3%到119%之间。在37℃下用胰酶处理结合物后，某些类型的PS含量增加，包括4型和14型。此外，与未处理的PS相比，在高碘酸盐激活的PS中引入了更高或更低水平的抗原-抗体反应，然后降低了某些血清型的PS。使用氧化和还原PS可以提供抗原-抗体结合和结合稳定性变化的早期迹象。