Hoonakker M E, Verhagen L M, Hendriksen C F M, van Els C A C M, Vandebriel R J, Sloots A, Han W G H
Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands; Faculty of Veterinary Medicine, Department Animals in Science and Society, Utrecht University, The Netherlands.
Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands; Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Biologicals. 2015 Mar;43(2):100-9. doi: 10.1016/j.biologicals.2014.12.002. Epub 2015 Jan 26.
Lot release testing of vaccines is primarily based on animal models that are costly, time-consuming and sometimes of questionable relevance. In order to reduce animal use, functional in vitro assays are being explored as an alternative approach for the current lot release testing paradigm. In this study, we present an evaluation of APC platforms assessing innate immune activation by whole cell Bordetella pertussis (wP) vaccines. Primary monocytes, monocyte-derived DC (moDC) and human monocyte/DC cell lines (MonoMac6 and MUTZ-3) were compared for their capacity to respond to wP vaccines of varying quality. To produce such vaccines, the production process of wP was manipulated, resulting in wP vaccines covering a range of in vivo potencies. The responses of MUTZ-3 cells and primary monocytes to these vaccines were marginal and these models were therefore considered inappropriate. Importantly, moDC and MonoMac6 cells responded to the wP vaccines and discriminated between vaccines of varying quality, although slight variations in the responses to wP vaccines of similar quality were also observed. This study provides a proof of principle for the use of in vitro APC platforms as part of a new strategy to assess wP vaccine lot consistency, though careful standardisation of assay conditions is necessary.
疫苗的批量放行检测主要基于动物模型，这些模型成本高、耗时且有时相关性存疑。为了减少动物使用，正在探索功能性体外检测作为当前批量放行检测模式的替代方法。在本研究中，我们对评估全细胞百日咳博德特氏菌（wP）疫苗诱导先天免疫激活的抗原呈递细胞（APC）平台进行了评估。比较了原代单核细胞、单核细胞衍生的树突状细胞（moDC）和人单核细胞/树突状细胞系（MonoMac6和MUTZ-3）对不同质量wP疫苗的反应能力。为生产此类疫苗，对wP的生产工艺进行了操控，从而得到了一系列体内效力不同的wP疫苗。MUTZ-3细胞和原代单核细胞对这些疫苗的反应微弱，因此这些模型被认为不合适。重要的是，moDC和MonoMac6细胞对wP疫苗有反应，并能区分不同质量的疫苗，不过对质量相似的wP疫苗的反应也存在细微差异。本研究为使用体外APC平台作为评估wP疫苗批次一致性新策略的一部分提供了原理证明，不过检测条件的仔细标准化是必要的。
