Q-VAX®, a whole cell, formalin-inactivated vaccine, is the only vaccine licensed for human use to protect against Coxiella burnetii, the cause of Q fever. Although this vaccine provides long-term protection, local and systemic reactogenic responses are common in previously sensitized individuals which prevents its use outside of Australia. Despite the importance of preventing these adverse reactions to develop widely accepted, novel vaccines against C. burnetii, little is understood about the underlying cellular mechanisms. This is mostly attributed to the use of a guinea pig reactogenicity model where complex cellular analysis is limited. To address this, we compared three different mouse strains develop a model of C. burnetii whole cell vaccine reactogenic responses. SKH1 and C57Bl/6, but not BALBc mice, develop local granulomatous reactions after either infection- or vaccine-induced sensitization. We evaluated local and systemic responses by measuring T cell populations from the vaccination site and spleen during elicitation using flow cytometry. Local reaction sites showed influx of IFNγ+ and IL17a+ CD4 T cells in sensitized mice compared with controls and a reduction in IL4+ CD4 T cells. Additionally, sensitized mice showed a systemic response to elicitation by an increase in IFNγ+ and IL17a+ CD4 T cells in the spleen. These results indicate that local and systemic C. burnetii reactogenic responses are consistent with a Th1 delayed-type hypersensitivity. Our experiments provide insights into the pathophysiology of C. burnetii whole cell vaccine reactogenicity and demonstrate that C57Bl/6 and SKH1 mice can provide a valuable model for evaluating the reactogenicity of novel C. burnetii vaccine candidates.

Q-VAX® 是一种全细胞福尔马林灭活疫苗，是唯一一种获准用于人类预防感染的疫苗伯氏柯克氏体，Q热的原因。尽管这种疫苗提供了长期保护，但局部和全身反应原性反应在以前致敏的个体中很常见，这阻止了它在澳大利亚以外的使用。尽管预防这些不良反应对于开发广泛接受的新型疫苗非常重要C.burnetii，对潜在的细胞机制知之甚少。这主要归因于使用豚鼠反应原性模型，其中复杂的细胞分析受到限制。为了解决这个问题，我们比较了三种不同的小鼠品系，开发了一个模型C.burnetii全细胞疫苗反应原性反应。SKH1 和 C57Bl/6，但不是 BALBc 小鼠，在感染或疫苗诱导的致敏后发生局部肉芽肿反应。我们通过使用流式细胞术在诱导过程中测量来自疫苗接种部位和脾脏的 T 细胞群来评估局部和全身反应。与对照组相比，致敏小鼠的局部反应部位显示 IFNγ+ 和 IL17a+ CD4 T 细胞流入，IL4+ CD4 T 细胞减少。此外，致敏小鼠通过脾脏中 IFNγ+ 和 IL17a+ CD4 T 细胞的增加显示出对诱导的全身反应。这些结果表明，局部和系统C.burnetii反应原性反应与 Th1 迟发型超敏反应一致。我们的实验提供了对病理生理学的见解C.burnetii全细胞疫苗反应原性并证明 C57Bl/6 和 SKH1 小鼠可以为评估新型疫苗的反应原性提供有价值的模型C.burnetii候选疫苗。