Quality control of pneumococcal conjugate vaccines

摘要：肺炎球菌的ps通过还原性胺化作用与载体蛋白共价连接。该方法采用高碘酸盐氧化PSs以引入醛基。高碘酸盐的氧化程度是共轭过程中重要的第一步。因此，高碘酸盐活化PSs的免疫化学特性可以为肺炎球菌结合疫苗的对照试验提供有用的信息。采用光散射比浊法对单价和7价肺炎球菌结合疫苗中PS的含量进行了定量分析。检测了高碘酸盐活化后再还原PS的抗体结合反应，应用速率比浊法定量测定PS的含量。使用这种方法，单个类型4,6b, 9V, 14,18c， 19F和23F的ps被发现在制造商指示值的82.3到119%之间。用胰蛋白酶在37℃下处理偶联物导致某些类型的PS含量增加，包括4型和14型。此外，与未处理的PS相比，高碘酸盐激活和还原的PS在某些血清型中引入了更高或更低水平的抗原-抗体反应。使用氧化和还原的PS可以提供抗原-抗体结合和偶联稳定性变化的早期指示。

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.