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脑膜炎球菌结合疫苗质量控制中热原检测试验的比较:单核细胞激活试验的适用性

A comparison of pyrogen detection tests in the quality control of meningococcal conjugate vaccines: The applicability of the Monocyte Activation Test.

作者信息

Fernandes Silva Vitor, da Silva Guedes Junior Daniel, da Silveira Ivna Alana, Santos Almeida Alessandra, de Paiva Conte Fernando, Fernandes Delgado Isabella, Caldeira Silva Cristiane, França Presgrave Octavio Augusto, Antunes de Mattos Katherine

机构信息

Departamento de Controle de Qualidade, Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.

Laboratório de Tecnologia Bacteriana, Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.

出版信息

Altern Lab Anim. 2018 Nov;46(5):255-272. doi: 10.1177/026119291804600506.

Abstract

The meningococcal C conjugate vaccine (MenCC) is an interesting model with which to test the efficacy of the Monocyte Activation Test (MAT) as an alternative method of pyrogen testing in the quality control of vaccines. The MenCC that has been produced by Bio-Manguinhos in Brazil is in the final development stage, and, as recommended in the guidelines for MenCC production, its pyrogen content must be determined by using the Limulus Amoebocyte Lysate (LAL) assay and the Rabbit Pyrogen Test (RPT). This represents an ideal opportunity to compare LAL and RPT data with data obtained by using a MAT system with cryopreserved whole blood and IL-6/IL-1β as marker readouts. In order to assess the compatibility of the MAT with MenCC, endotoxin and non-endotoxin pyrogen content was quantified by using MenCC samples spiked with lipopolysaccharide (LPS), lipoteichoic acid or zymosan standards. The presence of the aluminium-based adjuvant interfered with the MAT, increasing the readout of IL-1β in LPS-spiked MenCC batches. This infringed the product-specific validation criteria of the test, and led to IL-6 being chosen as the more suitable marker readout. No pyrogenic contaminants were identified in the MenCC batches tested, demonstrating consistency among the different systems (MAT, RPT and the LAL assay). In conclusion, the introduction of the MAT during MenCC development could contribute to the elimination of animal tests post-licensing, ensuring human protection based on an effective non-animal based method of quality control.

摘要

脑膜炎球菌C结合疫苗(MenCC)是一个有趣的模型,可用于测试单核细胞激活试验(MAT)作为疫苗质量控制中热原检测替代方法的有效性。巴西Bio-Manguinhos生产的MenCC处于最终开发阶段,按照MenCC生产指南的建议,其热原含量必须通过使用鲎试剂检测法(LAL)和家兔热原试验(RPT)来确定。这是一个将LAL和RPT数据与使用以冷冻保存的全血和IL-6/IL-1β作为标志物读数的MAT系统获得的数据进行比较的理想机会。为了评估MAT与MenCC的兼容性,通过使用添加了脂多糖(LPS)、脂磷壁酸或酵母聚糖标准品的MenCC样品来定量内毒素和非内毒素热原含量。铝基佐剂的存在干扰了MAT,增加了LPS添加的MenCC批次中IL-1β的读数。这违反了该测试的产品特异性验证标准,并导致选择IL-6作为更合适的标志物读数。在所测试的MenCC批次中未鉴定出热原性污染物,这表明不同系统(MAT、RPT和LAL检测)之间具有一致性。总之,在MenCC开发过程中引入MAT有助于在许可后消除动物试验,确保基于有效的非动物质量控制方法来保护人类。

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