Transient facial nerve paralysis (Bell's palsy) following intranasal delivery of a genetically detoxified mutant of Escherichia coli heat labile toxin.
Transient facial nerve paralysis (Bell's palsy) following intranasal delivery of a genetically detoxified mutant of Escherichia coli heat labile toxin.
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DOI：
10.1371/journal.pone.0006999
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发表时间：
2009-09-16
期刊：
影响因子：
3.7
通讯作者：
Rappuoli R
中科院分区：
文献类型：
--
作者：
Lewis DJ;Huo Z;Barnett S;Kromann I;Giemza R;Galiza E;Woodrow M;Thierry-Carstensen B;Andersen P;Novicki D;Del Giudice G;Rappuoli R
此前，面神经麻痹(贝尔氏麻痹)与鼻腔注射灭活流感病毒疫苗之间存在关联，该灭活流感病毒疫苗含有一种具有酶活性的大肠杆菌不耐热毒素(LT)佐剂。导致瘫痪的个人成分(S)未被确认，疫苗被撤回。参与两项同时进行的针对人类免疫缺陷病毒和结核病的鼻腔亚单位疫苗的非随机第一阶段临床试验的受试者，都使用了一种酶失活的无毒突变LT佐剂(LTK63)，并使用日记卡片和临床检查对不良事件进行了积极的随访。两名健康受试者在被动鼻腔注射LTK63后44天和60天出现一过性周围面神经麻痹，可能是神经节苷脂结合后逆行轴突运输或炎性免疫反应的结果，但对LTK63没有过度的免疫反应。虽然面神经对压迫的独特解剖易感性表明，神经结合LT衍生佐剂的鼻腔给药是不可取的，但基于经口、经皮和其他黏膜途径的长期安全性，它们作为局部或粘膜佐剂和抗原的持续研究似乎是有必要的。
An association was previously established between facial nerve paralysis (Bell's palsy) and intranasal administration of an inactivated influenza virosome vaccine containing an enzymatically active Escherichia coli Heat Labile Toxin (LT) adjuvant. The individual component(s) responsible for paralysis were not identified, and the vaccine was withdrawn. Subjects participating in two contemporaneous non-randomized Phase 1 clinical trials of nasal subunit vaccines against Human Immunodeficiency Virus and tuberculosis, both of which employed an enzymatically inactive non-toxic mutant LT adjuvant (LTK63), underwent active follow-up for adverse events using diary-cards and clinical examination. Two healthy subjects experienced transient peripheral facial nerve palsies 44 and 60 days after passive nasal instillation of LTK63, possibly a result of retrograde axonal transport after neuronal ganglioside binding or an inflammatory immune response, but without exaggerated immune responses to LTK63. While the unique anatomical predisposition of the facial nerve to compression suggests nasal delivery of neuronal-binding LT–derived adjuvants is inadvisable, their continued investigation as topical or mucosal adjuvants and antigens appears warranted on the basis of longstanding safety via oral, percutaneous, and other mucosal routes.
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影响因子：
1.4
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