An adenoviral vector-based mucosal vaccine is effective in protection against botulism.

An adenoviral vector-based mucosal vaccine is effective in protection against botulism.
复制标题

基于腺病毒载体的粘膜疫苗可有效防止肉毒杆菌毒性。

DOI:
10.1038/gt.2008.181
复制
发表时间:
2009-03
期刊:
影响因子:
5.1
通讯作者:
Zeng M
Zeng M
中科院分区:
医学3区
文献类型:
--
作者:
Xu Q;Pichichero ME;Simpson LL;Elias M;Smith LA;Zeng M

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将编码C型肉毒杆菌神经毒素重链C片段(HC50)的复制失效腺病毒载体作为黏膜疫苗,在小鼠模型中进行了评价。单次鼻腔接种腺病毒载体后2周,血清和粘膜分泌物中均有高水平的HC50特异性免疫球蛋白Ig G、Ig G1和Ig G2a和Ig A。抗原特异性血清抗体至少维持到第27周的较高水平。体外毒素中和实验表明,免疫血清对BoNT/C具有较强的中和能力。单次给药2×10~7 p.f.u。(空斑形成单位)对高达104× /C的攻击具有完全保护作用,保护性免疫在10~5~2×10~7MLD/f.u之间呈剂量依赖关系。腺病毒载体。此外,动物接受单次鼻腔给药2×10~7 p.f.u。免疫后27周,腺病毒载体可抵抗100×MLD50的攻击。对腺病毒有免疫力的动物也可以鼻腔免疫,并能抵抗BoNT/C的致死性攻击。这些结果表明,腺病毒载体是一种高效的基于基因的肉毒杆菌感染的黏膜疫苗。
A replication-incompetent adenoviral vector encoding the heavy chain C-fragment (HC50) of botulinum neurotoxin type C (BoNT/C) was evaluated as a mucosal vaccine against botulism in a mouse model. Single intranasal inoculation of the adenoviral vector elicited a high level of HC50-specific IgG, IgG1 and IgG2a in sera and IgA in mucosal secretions as early as 2 weeks after vaccination. The antigen-specific serum antibodies were maintained at a high level at least until the 27th week. Immune sera showed high potency in neutralizing BoNT/C as indicated by in vitro toxin neutralization assay. The mice receiving single dose of 2 × 107 p.f.u. (plaque-forming unit) of adenoviral vector were completely protected against challenge with up to 104 × MLD50 of BoNT/C. The protective immunity showed vaccine dose dependence from 105 to 2 × 107 p.f.u. of adenoviral vector. In addition, animals receiving single intranasal dose of 2 × 107 p.f.u. adenoviral vector could be protected against 100 × MLD50 27 weeks after vaccination. Animals with preexisting immunity to adenovirus could also be vaccinated intranasally and protected against lethal challenge with BoNT/C. These results suggest that the adenoviral vector is a highly effective gene-based mucosal vaccine against botulism.
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