Characterization of Classical Vaccines by Charge Detection Mass Spectrometry
Characterization of Classical Vaccines by Charge Detection Mass Spectrometry
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DOI：
10.1021/acs.analchem.1c01893
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发表时间：
2021-08-26
影响因子：
7.4
通讯作者：
Jarrold, Martin F.
中科院分区：
文献类型：
--
作者：
Miller, Lohra M.;Bond, Kevin M.;Jarrold, Martin F.
疫苗通过从单个蛋白质亚基到整个病毒的多个平台呈现疾病抗原来诱导免疫力。由于抗原大小存在巨大差异，用于疫苗表征的分析技术通常是特定于平台的。能够广泛、跨平台使用的单一、强大的分析技术将带来巨大的好处，并允许跨制造过程进行比较。跨越抗原质量范围的一种方法是电荷检测质谱法 (CDMS)。 CDMS 是一种单离子方法，可同时测量质荷比 (m/z) 和电荷，从而可以测量宽尺寸范围内异质分析物的精确质量分布。在这项工作中，CDMS 用于直接从商业样品中表征三种经典多价疫苗、灭活脊髓灰质炎疫苗 (IPOL)、RotaTeq 和 Gardasil-9 的抗原。对于每种疫苗，都检查了抗原纯度，在全病毒疫苗中检测到了空病毒颗粒。对于 IPOL，获得了有关甲醛交联程度的信息。 RotaTeq 在 61.06 MDa 处显示窄峰。双层粒子的质量略低于预期，表明大约有 10 个五角三聚体缺失。对于 Gardasil-9，疫苗的缓冲液交换导致了非常广泛的质量分布。然而，使用置换反应从铝佐剂中去除病毒样颗粒产生了具有窄峰的光谱。
Vaccines induce immunity by presenting disease antigens through several platforms ranging from individual protein subunits to whole viruses. Due to the large difference in antigen size, the analytical techniques employed for vaccine characterization are often platform-specific. A single, robust analytical technique capable of widespread, cross-platform use would be of great benefit and allow for comparisons across manufacturing processes. One method that spans the antigen mass range is charge detection mass spectrometry (CDMS). CDMS is a single-ion approach where the mass-to-charge ratio (m/z) and charge are measured simultaneously, allowing accurate mass distributions to be measured for heterogeneous analytes over a broad size range. In this work, CDMS was used to characterize the antigens from three classical multivalent vaccines, inactivated poliomyelitis vaccine (IPOL), RotaTeq, and Gardasil-9, directly from commercial samples. For each vaccine, the antigen purity was inspected, and in the whole virus vaccines, empty virus particles were detected. For IPOL, information on the extent of formaldehyde cross-linking was obtained. RotaTeq shows a narrow peak at 61.06 MDa. This is at a slightly lower mass than expected for the double-layer particle, suggesting that around 10 pentonal trimers are missing. For Gardasil-9, buffer exchange of the vaccine resulted in very broad mass distributions. However, removal of the virus-like particles from the aluminum adjuvant using a displacement reaction generated a spectrum with narrow peaks.