Hoonakker M E, Verhagen L M, van der Maas L, Metz B, Uittenbogaard J P, van de Waterbeemd B, van Els C A C M, van Eden W, Hendriksen C F M, Sloots A, Han W G H
Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands; Utrecht University, Faculty of Veterinary Medicine, Department Animals in Science and Society, Utrecht, The Netherlands.
Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands; Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Vaccine. 2016 Aug 17;34(37):4429-36. doi: 10.1016/j.vaccine.2016.07.011. Epub 2016 Jul 21.
Whole cell Bordetella pertussis (wP) vaccines are still used in many countries to protect against the respiratory disease pertussis. The potency of whole-cell pertussis vaccine lots is determined by an intracerebral challenge test (the Kendrick test). This test is criticized due to lack of immunological relevance of the read-out after an intracerebral challenge with B. pertussis. The alternative in vivo test, which assesses specific antibody levels in serum after wP vaccination, is the Pertussis Serological Potency test (PSPT). Although the PSPT focuses on a parameter that contributes to protection, the protective immune mechanisms after wP vaccination includes more elements than specific antibody responses only. In this study, additional parameters were investigated, i.e. circulating pro-inflammatory cytokines, antibody specificity and T helper cell responses and it was evaluated whether they can be used as complementary readout parameters in the PSPT to assess wP lot quality. By deliberate manipulation of the vaccine preparation procedure, a panel of high, intermediate and low quality wP vaccines were made. The results revealed that these vaccines induced similar IL-6 and IP10 levels in serum 4h after vaccination (innate responses) and similar antibody levels directed against the entire bacterium. In contrast, the induced antibody specificity to distinct wP antigens differed after vaccination with high, intermediate and low quality wP vaccines. In addition, the magnitude of wP-induced Th cell responses (Th17, Th1 and Th2) was reduced after vaccination with a wP vaccine of low quality. T cell responses and antibody specificity are therefore correlates of qualitative differences in the investigated vaccines, while the current parameter of the PSPT alone was not sensitive enough to distinguish between vaccines of different qualities. This study demonstrates that assessment of the magnitude of Th cell responses and the antigen specificity of antibodies induced by wP vaccination could form valuable complementary parameters to the PSPT.
全细胞百日咳疫苗（wP）仍在许多国家用于预防呼吸道疾病百日咳。全细胞百日咳疫苗批次的效力通过脑内攻毒试验（肯德里克试验）来确定。由于用百日咳博德特氏菌进行脑内攻毒后的检测结果缺乏免疫学相关性，该试验受到批评。替代的体内试验是百日咳血清学效力试验（PSPT），它评估wP疫苗接种后血清中的特异性抗体水平。尽管PSPT关注的是有助于提供保护的一个参数，但wP疫苗接种后的保护性免疫机制包含的要素不止特异性抗体反应。在本研究中，对其他参数进行了研究，即循环促炎细胞因子、抗体特异性和辅助性T细胞反应，并评估了它们是否可用作PSPT中的补充检测参数以评估wP批次的质量。通过有意操纵疫苗制备程序，制备了一组高、中、低质量的wP疫苗。结果显示，这些疫苗在接种后4小时诱导血清中产生相似的IL-6和IP10水平（先天反应）以及针对整个细菌的相似抗体水平。相比之下，用高、中、低质量的wP疫苗接种后，诱导产生的针对不同wP抗原的抗体特异性有所不同。此外，用低质量的wP疫苗接种后，wP诱导的Th细胞反应（Th17、Th1和Th2）的强度降低。因此，T细胞反应和抗体特异性与所研究疫苗的质量差异相关，而仅PSPT的当前参数不足以灵敏地区分不同质量的疫苗。本研究表明，评估wP疫苗接种诱导的Th细胞反应强度和抗体的抗原特异性可成为PSPT中有价值的补充参数。
