An improved vaccine for prevention of respiratory tularemia caused by Francisella tularensis SchuS4 strain.
An improved vaccine for prevention of respiratory tularemia caused by Francisella tularensis SchuS4 strain.
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DOI：
10.1016/j.vaccine.2008.07.051
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发表时间：
2008-09-26
期刊：
影响因子：
5.5
通讯作者：
Metzger DW
中科院分区：
文献类型：
--
作者：
Bakshi CS;Malik M;Mahawar M;Kirimanjeswara GS;Hazlett KR;Palmer LE;Furie MB;Singh R;Melendez JA;Sellati TJ;Metzger DW
到目前为止，用图拉氏弗朗西斯杆菌活疫苗株(LVS)突变株免疫小鼠未能诱导C57BL/6小鼠免受图拉氏杆菌强毒株SchuS4的攻击。我们以前曾报道过一株缺乏铁超氧化物歧化酶(SodBFt)的图拉氏F菌突变体对小鼠的氧化应激敏感，并使其毒力减弱。在此，我们评估了该突变体作为疫苗候选对由图拉氏福氏杆菌SchuS4引起的呼吸性图拉热症的有效性。C57BL/6小鼠鼻腔免疫(I.N.)与苏打突变体和挑战I.N。致死剂量的图拉氏酵母SchuS4。SodBFt免疫组对SchuS4攻击的保护力高于LVS免疫组。在SchuS4攻击后，SodBFt接种的小鼠的肺、肝和脾中的细菌负荷显著减少，促炎细胞因子的调节产生，以及较轻的组织病理损害。SodBFt疫苗能诱导小鼠产生较强的体液免疫应答，对SchuS4的保护需要免疫小鼠体内的CD4和CD8T细胞。SodBFt突变体显示伴侣蛋白DNAK、GroEL和BfR水平上调，已被证明对产生针对Francisella感染的有效免疫反应是重要的。总而言之，这项研究描述了一种针对呼吸性图拉热症的改进的活疫苗候选，它具有比LVS更弱的毒力和更强的保护效力。
Vaccination of mice with Francisella tularensis live vaccine strain (LVS) mutants described so far have failed to induce protection in C57BL/6 mice against challenge with the virulent strain F. tularensis SchuS4. We previously have reported that a mutant of F. tularensis LVS deficient in iron superoxide dismutase (sodBFt) is hypersensitive to oxidative stress and attenuated for virulence in mice. Herein, we evaluated the efficacy of this mutant as a vaccine candidate against respiratory tularemia caused by F. tularensis SchuS4. C57BL/6 mice were vaccinated intranasally (i.n.) with the sodBFt mutant and challenged i.n. with lethal doses of F. tularensis SchuS4. The level of protection against SchuS4 challenge was higher in sodBFt vaccinated group as compared to the LVS vaccinated mice. SodBFt vaccinated mice following SchuS4 challenge exhibited significantly reduced bacterial burden in lungs, liver and spleen, regulated production of pro-inflammatory cytokines and less severe histopathological lesions compared to the LVS vaccinated mice. The sodBFt vaccination induced a potent humoral immune response and protection against SchuS4 required both CD4 and CD8 T cells in the vaccinated mice. SodBFt mutants revealed upregulated levels of chaperonine proteins DnaK, GroEL and Bfr that have been shown to be important for generation of a potent immune response against Francisella infection. Collectively, this study describes an improved live vaccine candidate against respiratory tularemia that has an attenuated virulence and enhanced protective efficacy than the LVS.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1073/pnas.0602582103
发表时间：
2006-08-22
影响因子：
11.1
作者：
Gil, Horacio;Platz, Gabrielle J.;Thanassi, David G.
通讯作者：
Thanassi, David G.
影响因子：
30.8
作者：
Larsson, P;Oyston, PCF;Titball, RW
通讯作者：
Titball, RW
影响因子：
3.1
作者：
Lee, Bai-Yu;Horwitz, Marcus A.;Clemens, Daniel L.
通讯作者：
Clemens, Daniel L.
影响因子：
5.5
作者：
KuoLee, Rhonda;Harris, Greg;Chen, Wangxue
通讯作者：
Chen, Wangxue