Contributions of edema factor and protective antigen to the induction of protective immunity by Bacillus anthracis edema toxin as an intranasal adjuvant.
Contributions of edema factor and protective antigen to the induction of protective immunity by Bacillus anthracis edema toxin as an intranasal adjuvant.
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DOI：
10.4049/jimmunol.0902795
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发表时间：
2010-11-15
期刊：
影响因子：
--
通讯作者：
Boyaka PN
中科院分区：
文献类型：
--
作者：
Duverger A;Carré JM;Jee J;Leppla SH;Cormet-Boyaka E;Tang WJ;Tomé D;Boyaka PN
我们发现，炭疽杆菌保护性抗原(PA)与降低腺苷环化酶活性的炭疽杆菌水肿因子(EF)突变体(即EF-S414N)鼻腔联合应用可增强抗PAAb反应，但也可作为联合应用无关AGS的粘膜佐剂。为了阐明水肿型毒素(EdTx)在其佐剂作用中的作用，我们研究了缺乏与EF(PA-U7)结合能力的PA突变体或另一种允许细胞摄取EF但不能有效地将其转位到胞浆(PA-DFF)的突变体如何影响EdTx诱导的适应性免疫。在体外，天然EdTx可促进巨噬细胞和B淋巴细胞表达共刺激分子，并促进颈部淋巴结细胞产生广泛的细胞因子反应。当EF+PA-DFF或PA-U7替代PA处理细胞时，这些作用被减弱或消除。我们还用鼠疫耶尔森菌F1和LcrVAgs的重组融合蛋白(F1-V)以及由野生型或突变体PA和EF组成的EdTx变体经鼻免疫小鼠。对F1-V或EdTx组分(即PA和EF)的血清和粘膜抗体反应的分析表明，接受PA-U7而不是PA的小鼠没有佐剂活性。相反，与PA-DFF联合免疫可增强血清抗体反应。最后，用天然PA和缺乏腺苷环化酶活性的EF突变体(EF-K346R)免疫并不能增强抗体应答。总而言之，EdTx作为粘膜佐剂需要一个功能齐全的PA和最低限度的腺苷环化酶活性。
We have shown that intranasal coapplication of Bacillus anthracis protective Ag (PA) together with a B. anthracis edema factor (EF) mutant having reduced adenylate cyclase activity (i.e., EF-S414N) enhances anti-PAAb responses, but also acts as a mucosal adjuvant for coadministered unrelated Ags. To elucidate the role of edema toxin (EdTx) components in its adjuvanticity, we examined how a PA mutant lacking the ability to bind EF (PA-U7) or another mutant that allows the cellular uptake of EF, but fails to efficiently mediate its translocation into the cytosol (PA-dFF), would affect EdTx-induced adaptive immunity. Native EdTx promotes costimulatory molecule expression by macrophages and B lymphocytes, and a broad spectrum of cytokine responses by cervical lymph node cells in vitro. These effects were reduced or abrogated when cells were treated with EF plus PA-dFF, or PA-U7 instead of PA. We also intranasally immunized groups of mice with a recombinant fusion protein of Yersinia pestis F1 and LcrVAgs (F1-V) together with EdTx variants consisting of wild-type or mutants PA and EF. Analysis of serum and mucosal Ab responses against F1-V or EdTx components (i.e., PA and EF) revealed no adjuvant activity in mice that received PA-U7 instead of PA. In contrast, coimmunization with PA-dFF enhanced serum Ab responses. Finally, immunization with native PA and an EF mutant lacking adenylate cyclase activity (EF-K346R) failed to enhance Ab responses. In summary, a fully functional PA and a minimum of adenylate cyclase activity are needed for EdTx to act as a mucosal adjuvant.
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DOI：
10.1073/pnas.93.22.12531
发表时间：
1996-10-29
影响因子：
11.1
作者：
Ballard, JD;Collier, RJ;Starnbach, MN
通讯作者：
Starnbach, MN
影响因子：
64.8
作者：
Drum, CL;Yan, SZ;Tang, WJ
通讯作者：
Tang, WJ
影响因子：
6
作者：
Fischer, R;McGhee, JR;Boyaka, PN
通讯作者：
Boyaka, PN
影响因子：
6.4
作者：
Cao, HY;Agrawal, D;Lu, YC
通讯作者：
Lu, YC
DOI：
10.1073/pnas.94.22.12059
发表时间：
1997-10-28
影响因子：
11.1
作者：
Goletz, TJ;Klimpel, KR;Berzofsky, JA
通讯作者：
Berzofsky, JA