Quality control of pneumococcal conjugate vaccines

总结： 肺炎球菌PS通过还原胺化作用与载体蛋白共价连接。在该方法中，PS被高碘酸盐氧化以引入醛基。 高碘酸盐氧化的程度是缀合过程中重要的第一步。 因此，高碘酸活化PS的免疫化学表征可以为肺炎球菌结合疫苗的控制测试提供有用的信息。 本研究的目的是使用光散射比浊法定量分析单价和7价肺炎球菌结合疫苗中的PS含量。 用速率散射比浊法定量测定了高碘酸盐活化和还原PS的抗体结合反应。使用该方法，发现4、6 B、9V、14、18 C、19 F和23 F型PS的范围为制造商指示值的82.3%至119%。 在37 ℃下用胰蛋白酶处理缀合物导致某些类型（包括类型4和14）的PS含量测量增加。 此外，与未处理的PS相比，在高碘酸盐活化然后降低的PS中引入了更高或更低水平的抗原-抗体反应。 氧化和还原PS的使用可以提供抗原-抗体结合和缀合物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.