Vaccine and Immunotherapy Center, Massachusetts General Hospital, Boston, MA, United States.
InnatOss Laboratories B.V., Oss, Netherlands.
Front Immunol. 2022 Jun 23;13:886698. doi: 10.3389/fimmu.2022.886698. eCollection 2022.
Q fever is a zoonotic disease caused by the highly infectious Gram-negative coccobacillus, (). The Q fever vaccine Q-VAX is characterised by high reactogenicity, requiring individuals to be pre-screened for prior exposure before vaccination. To date it remains unclear whether vaccine side effects in pre-exposed individuals are associated with pre-existing adaptive immune responses to or are also a function of innate responses to Q-VAX. In the current study, we measured innate and adaptive cytokine responses to and compared these among individuals with different pre-exposure status. Three groups were included: n=98 Dutch blood bank donors with unknown exposure status, n=95 Dutch village inhabitants with known natural exposure status to during the Dutch Q fever outbreak of 2007-2010, and n=96 Australian students receiving Q-VAX vaccination in 2021. Whole blood cytokine responses following stimulation with heat-killed were assessed for IFNγ, IL-2, IL-6, IL-10, TNFα, IL-1β, IP-10, MIP-1α and IL-8. Serological data were collected for all three cohorts, as well as data on skin test and self-reported vaccine side effects and clinical symptoms during past infection. IFNγ, IP-10 and IL-2 responses were strongly elevated in individuals with prior antigen exposure, whether through infection or vaccination, while IL-1β, IL-6 and TNFα responses were slightly increased in naturally exposed individuals only. High dimensional analysis of the cytokine data identified four clusters of individuals with distinct cytokine response signatures. The cluster with the highest levels of adaptive cytokines and antibodies comprised solely individuals with prior exposure to , while another cluster was characterized by high innate cytokine production and an absence of -induced IP-10 production paired with high baseline IP-10 levels. Prior exposure status was partially associated with these signatures, but could not be clearly assigned to a single cytokine response signature. Overall, Q-VAX vaccination and natural infection were associated with comparable cytokine response signatures, largely driven by adaptive cytokine responses. Neither individual innate and adaptive cytokine responses nor response signatures were associated retrospectively with clinical symptoms during infection or prospectively with side effects post-vaccination.
Q 热是一种由高度传染性的革兰氏阴性球杆菌引起的人畜共患病。Q 热疫苗 Q-VAX 的特点是高反应原性，需要对个体进行预先筛选，以确定其在接种疫苗前是否有暴露史。迄今为止，尚不清楚预先暴露个体的疫苗副作用是否与预先存在的对的适应性免疫反应有关，还是对 Q-VAX 的固有反应也是一个功能。在本研究中，我们测量了对和的先天和适应性细胞因子反应，并比较了不同预先暴露状态个体之间的差异。包括三组：n=98 名荷兰献血者，其暴露状态未知；n=95 名荷兰村民，他们在 2007-2010 年荷兰 Q 热爆发期间有已知的自然暴露于的状态；n=96 名澳大利亚学生，他们在 2021 年接种了 Q-VAX 疫苗。用热灭活刺激后，评估全血细胞因子对 IFNγ、IL-2、IL-6、IL-10、TNFα、IL-1β、IP-10、MIP-1α 和 IL-8 的反应。对所有三组都收集了血清学数据，以及皮肤试验数据、自我报告的疫苗副作用数据和过去感染期间的临床症状数据。在有先前抗原暴露的个体中，无论是通过感染还是接种疫苗，IFNγ、IP-10 和 IL-2 反应均强烈升高，而仅在自然暴露个体中，IL-1β、IL-6 和 TNFα 反应略有升高。细胞因子数据的高维分析确定了四个具有不同细胞因子反应特征的个体群。具有最高水平的适应性细胞因子和抗体的群体仅由先前接触过的个体组成，而另一个群体的特点是高固有细胞因子产生和缺乏诱导的 IP-10 产生，同时基础 IP-10 水平较高。先前的暴露状态与这些特征部分相关，但不能明确分配给单个细胞因子反应特征。总体而言，Q-VAX 疫苗接种和自然感染与类似的细胞因子反应特征相关，主要由适应性细胞因子反应驱动。个体的先天和适应性细胞因子反应以及反应特征均与感染期间的临床症状无关，也与接种疫苗后的副作用无关。
