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首页> 外文期刊>Vaccine >Potent tetravalent replicon vaccines against botulinum neurotoxins using DNA-based Semliki forest virus replicon vectors.
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Potent tetravalent replicon vaccines against botulinum neurotoxins using DNA-based Semliki forest virus replicon vectors.

机译：使用基于DNA的Semliki森林病毒复制子载体对抗肉毒杆菌神经毒素的有效四价复制子疫苗。

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Human botulism is commonly associated with botulinum neurotoxin (BoNT) serotypes A, B, E and F. This suggests that the greatest need is for a tetravalent vaccine that provides protection against all four of these serotypes. In current study, we investigated the feasibility of generating several tetravalent vaccines that protected mice against the four serotypes. Firstly, monovalent replicon vaccine against BoNT induced better antibody response and protection than that of corresponding conventional DNA vaccine. Secondly, dual-expression DNA replicon pSCARSE/FHc or replicon particle VRP-E/FHc vaccine was well resistant to the challenge of BoNT/E and BoNT/F mixture as a combination vaccine composed of two monovalent replicon vaccines. Finally, the dual-expression DNA replicon or replicon particle tetravalent vaccine could simultaneously and effectively neutralize and protect the four BoNT serotypes. Protection correlated directly with serum ELISA titers and neutralization antibody levels to BoNTs. Therefore, replicon-based DNA or particle might be effective vector to develop BoNT vaccines, which might be more desirable for use in clinical application than the conventional DNA vaccines. Our studies demonstrate the utility of combining dual-expression DNA replicon or replicon particle vaccines into multi-agent formulations as potent tetravalent vaccines for eliciting protective responses to four serotypes of BoNTs.
机译：人肉毒杆菌中毒通常与肉毒杆菌神经毒素（BoNT）血清型A，B，E和F相关。这表明最需要的是能提供针对所有四种血清型的保护作用的四价疫苗。在当前的研究中，我们调查了产生几种保护小鼠免受四种血清型侵害的四价疫苗的可行性。首先，针对BoNT的单价复制子疫苗比相应的常规DNA疫苗诱导更好的抗体反应和保护。其次，双表达DNA复制子pSCARSE / FHc或复制子颗粒VRP-E / FHc疫苗对BoNT / E和BoNT / F混合物的攻击具有很好的抵抗力，这是由两种单价复制子疫苗组成的组合疫苗。最后，双表达DNA复制子或复制子颗粒四价疫苗可以同时有效地中和和保护四种BoNT血清型。保护与血清ELISA滴度和BoNT的中和抗体水平直接相关。因此，基于复制子的DNA或颗粒可能是开发BoNT疫苗的有效载体，与传统的DNA疫苗相比，在临床应用中可能更需要BoNT疫苗。我们的研究表明，将双表达DNA复制子或复制子颗粒疫苗组合为多剂制剂，作为有效的四价疫苗，可引起对四种血清型BoNT的保护反应。

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