The Feasibility of Using Coxiella burnetii Avirulent Nine Mile Phase II Viable Bacteria as a Live Attenuated Vaccine Against Q fever.
The Feasibility of Using Coxiella burnetii Avirulent Nine Mile Phase II Viable Bacteria as a Live Attenuated Vaccine Against Q fever.
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DOI：
10.3389/fimmu.2021.754690
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发表时间：
2021
影响因子：
7.3
通讯作者：
Zhang G
中科院分区：
文献类型：
--
作者：
Kumaresan V;Alam S;Zhang Y;Zhang G
本研究旨在探讨活的伯内特念珠菌无毒力的九英里 II 期 (NMII) 是否能够引发针对强毒 NM I 期 (NMI) 感染的保护性免疫。有趣的是，用活 NMII 免疫的小鼠在免疫后的不同时间点对 NMI 感染产生了显着的保护作用。活的 NMII 在小鼠中诱导剂量依赖性 NMI 特异性 IgG 反应，但所有剂量的 NMII 免疫小鼠都提供相似水平的保护。比较不同的免疫途径表明，鼻内免疫的小鼠表现出明显高于其他免疫途径的保护水平。存活的 NMII 诱导与福尔马林灭活的 NMI 疫苗 (PIV) 类似水平的针对 NMI 攻击的长期保护的观察表明，存活的 NMII 细菌可以诱导与 PIV 类似水平的针对有毒 NMI 攻击的长期保护。活的 NMII 还诱导显着的保护作用，以抵抗有毒的 Priscilla 和 Scurry 菌株的攻击，这表明活的 NMII 可以引起广泛的保护。来自活的 NMII 免疫小鼠的免疫血清和脾细胞对 NMI 感染有保护作用，但接受免疫血清的小鼠不能控制 NMI 复制。此外，活的 NMII 对野生型、CD4+ T 细胞缺陷和 CD8+ T 细胞缺陷小鼠提供了相当水平的保护，对 B 细胞缺陷小鼠提供了部分保护。然而，NMII 免疫的 T 细胞缺陷小鼠无法阻止伯氏念珠菌复制。因此，B 细胞和 T 细胞都是 NMII 诱导的保护性免疫所需的，但 T 细胞可能发挥关键作用。总的来说，这项研究证明了使用无毒 NMII 作为人类 Q 热减毒活疫苗的可行性。
This study aimed to explore if viable C. burnetii avirulent Nine Mile phase II (NMII) can elicit protective immunity against virulent NM phase I (NMI) infection. Interestingly, mice immunized with viable NMII elicited significant protection against NMI infection at different time points post-immunization. Viable NMII induced a dose-dependent NMI-specific IgG response in mice, but all doses of NMII-immunized mice conferred a similar level of protection. Comparing different routes of immunization indicated that intranasally immunized mice showed significantly higher levels of protection than other immunization routes. The observation that viable NMII induced a similar level of long-term protection against NMI challenge as the formalin-inactivated NMI vaccine (PIV) suggests that viable NMII bacteria can induce a similar level of long-term protection against virulent NMI challenge as the PIV. Viable NMII also induced significant protection against challenge with virulent Priscilla and Scurry strains, suggesting that viable NMII can elicit broad protection. Immune sera and splenocytes from viable NMII-immunized mice are protective against NMI infection, but immune serum-receiving mice did not control NMI replication. Additionally, viable NMII conferred a comparable level of protection in wild-type, CD4+ T cell-deficient, and CD8+ T cell-deficient mice, and partial protection in B cell-deficient mice. However, NMII-immunized T cell-deficient mice were unable to prevent C. burnetii replication. Thus, both B cells and T cells are required for viable NMII-induced protective immunity but T cells may play a critical role. Collectively, this study demonstrates the feasibility of using avirulent NMII as a live attenuated vaccine against human Q fever.