Highly purified mutant E112K of cholera toxin elicits protective lung mucosal immunity to diphtheria toxin.

Highly purified mutant E112K of cholera toxin elicits protective lung mucosal immunity to diphtheria toxin.
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高度纯化的霍乱毒素突变体 E112K 可引发对白喉毒素的保护性肺粘膜免疫。

DOI:
10.1016/s0264-410x(01)00412-1
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发表时间:
2001
期刊:
影响因子:
5.5
通讯作者:
McGhee,JR
McGhee,JR
中科院分区:
医学3区
文献类型:
--
作者:
Ohmura,M;Yamamoto,M;Kiyono,H;Fujihashi,K;Takeda,Y;McGhee,JR

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We demonstrated that the mutant of cholera toxin (mCT) E112K which was LPS-free supported the induction of protective immunity in mucosal (e.g. lung lavage) and systemic (e.g. serum) compartments when given nasally with vaccine-grade diphtheria toxoid (DT) to mice. Significant DT-specific mucosal IgA antibody (Ab) and serum IgG, IgA and IgM Ab responses were induced when LPS-depleted mCT E112K or native CT (nCT) was co-administered nasally with DT. The analysis of DT-specific Ab-forming cell (AFC) responses supported the Ab titers and significant numbers of DT-specific IgA AFC were present in the lungs, nasal passages and submandibular glands. Furthermore, DT-specific IgG AFC in cervical lymph nodes (CLN) and the spleen were induced in mice administered with DT nasally with either mCT or nCT. The analysis of antigen-specific T cell responses revealed that increased DT-specific CD4+T cell proliferative and Th2-type cytokine responses were induced in mice nasally-immunized with DT and the LPS-free form of mCT. The neutralization of diphtheria toxin by Abs showed that DT-specific IgG Ab responses in serum and lung lavages of mice immunized with DT and mCT were protective. Furthermore, it was shown that an IgA-enriched fraction of lung lavages possessed diphtheria toxin-specific neutralizing activity. These results are the first demonstration that nasally co-administered mCT E112K can induce DT-specific protective Ab responses in mucosal compartments (e.g. lung lavages and the lungs).
DOI: 10.4049/jimmunol.155.10.4621
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作者:
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