Contributions of lipopolysaccharide and the type IVB secretion system to Coxiella burnetii vaccine efficacy and reactogenicity.
Contributions of lipopolysaccharide and the type IVB secretion system to Coxiella burnetii vaccine efficacy and reactogenicity.
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DOI：
10.1038/s41541-021-00296-6
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发表时间：
2021-03-19
期刊：
影响因子：
9.2
通讯作者：
Heinzen RA
中科院分区：
文献类型：
--
作者：
Long CM;Beare PA;Cockrell DC;Fintzi J;Tesfamariam M;Shaia CI;Heinzen RA
伯氏柯克斯体是人畜共患病Q热的病原体。目前的人类Q热疫苗Q-VAX®是一种固定的全细胞疫苗(WCV)，仅在澳大利亚获得使用许可。在对伯氏梭菌有免疫力的人中，使用伯氏梭菌WCV与皮肤过敏反应有关，从而限制了更广泛的使用。因此，需要一种反应性较低的疫苗。在这里，我们研究了伯氏梭菌Dot/ICM型IVB分泌系统(T4BSS)和脂多糖(LPS)在固定WCVS保护和反应性中的作用。在9英里I期强毒株中缺失了一个包含23个点/icm基因的32.5kb的 区域，并在豚鼠感染、疫苗攻击和疫苗后超敏反应模型中进行了评估。NmI∆Dot/icm株是无毒的，对伯氏梭菌的强烈攻击具有保护作用，并且与nmi相比，表现出潜在的改变的反应性。9株产生粗大内毒素的Mile阶段II(NMII)菌株也进行了类似的测试。作为一种WCV，NMI明显比NMII具有更强的保护作用；然而，两种疫苗表现出相似的反应原性。综上所述，我们的结果表明，与第一阶段的内毒素一样，伯氏梭菌的完全毒力需要T4BSS。相反，与第一阶段的内毒素不同，T4BSS不需要疫苗诱导的保护。LPS的长度似乎并不有助于反应性，而T4BSS可能有助于这种反应。NmiWCVDot/∆代表了一种具有完全疫苗效力的I期毒株，说明了转基因伯氏梭菌作为改良的WCVS的潜力。
Coxiella burnetii is the bacterial causative agent of the zoonosis Q fever. The current human Q fever vaccine, Q-VAX®, is a fixed, whole cell vaccine (WCV) licensed solely for use in Australia. C. burnetii WCV administration is associated with a dermal hypersensitivity reaction in people with pre-existing immunity to C. burnetii, limiting wider use. Consequently, a less reactogenic vaccine is needed. Here, we investigated contributions of the C. burnetii Dot/Icm type IVB secretion system (T4BSS) and lipopolysaccharide (LPS) in protection and reactogenicity of fixed WCVs. A 32.5 kb region containing 23 dot/icm genes was deleted in the virulent Nine Mile phase I (NMI) strain and the resulting mutant was evaluated in guinea pig models of C. burnetii infection, vaccination-challenge, and post-vaccination hypersensitivity. The NMI ∆dot/icm strain was avirulent, protective as a WCV against a robust C. burnetii challenge, and displayed potentially altered reactogenicity compared to NMI. Nine Mile phase II (NMII) strains of C. burnetii that produce rough LPS, were similarly tested. NMI was significantly more protective than NMII as a WCV; however, both vaccines exhibited similar reactogenicity. Collectively, our results indicate that, like phase I LPS, the T4BSS is required for full virulence by C. burnetii. Conversely, unlike phase I LPS, the T4BSS is not required for vaccine-induced protection. LPS length does not appear to contribute to reactogenicity while the T4BSS may contribute to this response. NMI ∆dot/icm represents an avirulent phase I strain with full vaccine efficacy, illustrating the potential of genetically modified C. burnetii as improved WCVs.
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影响因子：
6.7
作者：
Carey KL;Newton HJ;Lührmann A;Roy CR
通讯作者：
Roy CR
影响因子：
6.4
作者：
Beare PA;Gilk SD;Larson CL;Hill J;Stead CM;Omsland A;Cockrell DC;Howe D;Voth DE;Heinzen RA
通讯作者：
Heinzen RA
影响因子：
13.6
作者：
Abe, T;Yamaki, K;Hirai, K
通讯作者：
Hirai, K
影响因子：
3.1
作者：
Hoover, TA;Culp, DW;Thompson, HA
通讯作者：
Thompson, HA
DOI：
10.1177/09680519000060050701
发表时间：
2000-01-01
期刊：
JOURNAL OF ENDOTOXIN RESEARCH
影响因子：
--
作者：
Ftácek, P;Skultéty, L;Toman, R
通讯作者：
Toman, R