Soluble antigens derived from Coxiella burnetii elicit protective immunity in three animal models without inducing hypersensitivity.
Soluble antigens derived from Coxiella burnetii elicit protective immunity in three animal models without inducing hypersensitivity.
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DOI：
10.1016/j.xcrm.2021.100461
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发表时间：
2021-12-21
期刊：
影响因子：
--
通讯作者：
Samuel JE
中科院分区：
文献类型：
--
作者：
Gregory AE;van Schaik EJ;Fratzke AP;Russell-Lodrigue KE;Farris CM;Samuel JE
Q热是由胞内细菌伯纳氏杆菌引起的，在美国还没有批准的疫苗。福尔马林灭活的全细胞疫苗（WCV）提供单剂量的长期保护，但对疫苗反应性的担忧仍然存在。因此，我们寻求另一种方法，即从克隆衍生的无毒NMII菌株中纯化原生伯纳蒂梭菌抗原。一种可溶性细菌提取物，称为Sol II，可诱导高滴度、高亲和力的抗体，并诱导CD4 T细胞反应，从而在幼稚小鼠中提供保护。此外，在三种动物模型中，Sol II对肺部伯氏原体的攻击有保护作用，而不会引起过敏。一种nmi衍生的提取物，Sol I，进一步增强了保护，超过了WCV金标准。总的来说，这些数据代表了一种设计高效、无反应性Q热疫苗的有希望的方法。在预致敏豚鼠中没有疫苗介导的超敏反应的证据。Q热免疫进一步提高了Q热的保护作用。Q热是一种人畜共患疾病，没有广泛批准的疫苗，对公共卫生和国家安全构成严重威胁。在这项研究中，Gregory等人表明，一种可溶性细菌提取物既安全，又对三种感染动物模型的Q热提供了显著的保护。
Q fever is caused by the intracellular bacterium Coxiella burnetii, for which there is no approved vaccine in the United States. A formalin-inactivated whole-cell vaccine (WCV) from virulent C. burnetii NMI provides single-dose long-lived protection, but concerns remain over vaccine reactogenicity. We therefore sought an alternate approach by purifying native C. burnetii antigens from the clonally derived avirulent NMII strain. A soluble bacterial extract, termed Sol II, elicits high-titer, high-avidity antibodies and induces a CD4 T cell response that confers protection in naive mice. In addition, Sol II protects against pulmonary C. burnetii challenge in three animal models without inducing hypersensitivity. An NMI-derived extract, Sol I, enhances protection further and outperforms the WCV gold standard. Collectively, these data represent a promising approach to design highly effective, non-reactogenic Q fever vaccines. Solubilized fraction is purified from C. burnetii phase II cell lysate (Sol II) Sol II elicits protection in mice, guinea pigs, and macaques against Q fever No evidence of vaccine-mediated hypersensitivity in pre-sensitized guinea pigs Q fever protection improved further by Sol I immunization Q fever is a zoonotic disease with no widely approved vaccine that poses a serious threat to public health and national security. In this study, Gregory et al. show that a soluble bacterial extract is both safe and provides significant protection against Q fever in three animal models of infection.
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