抗肉毒中毒重组类毒素疫苗。
Recombinant holotoxoid vaccine against botulism.
作者信息
Pier Christina L, Tepp William H, Bradshaw Marite, Johnson Eric A, Barbieri Joseph T, Baldwin Michael R
机构信息
Food Research Institute, University of Wisconsin, Madison, Wisconsin, USA.
出版信息
Infect Immun. 2008 Jan;76(1):437-42. doi: 10.1128/IAI.00843-07. Epub 2007 Oct 29.
The botulinum neurotoxins (BoNT) are the most toxic proteins for humans and designated "Category A Select Agents." The current vaccine against botulism is in limited supply, and there is a need to develop new vaccine strategies. A recombinant BoNT/A toxoid was produced in Clostridium botulinum that contained a double amino acid substitution, R363A Y365F (termed BoNT/A(RYM)). BoNT/A(RYM) was noncatalytic for SNAP25 and nontoxic for mice. Immunization with BoNT/A(RYM) protected mice from challenge at levels that were similar to chemically inactivated BoNT/A toxoid. BoNT/A(RYM) elicited an immune response against the light-chain and heavy-chain components of the toxin. Neutralizing anti-BoNT/A(RYM) sera blocked BoNT toxicity in primary cortical neurons and blocked ganglioside binding by the heavy chain. BoNT/A(RYM) represents a viable vaccine candidate for a holotoxoid against botulism.
肉毒杆菌神经毒素（BoNT）是对人类毒性最强的蛋白质，被指定为“A类选择性制剂”。目前的抗肉毒中毒疫苗供应有限，因此需要开发新的疫苗策略。在肉毒梭菌中产生了一种重组BoNT/A类毒素，其含有双氨基酸取代，即R363A Y365F（称为BoNT/A(RYM)）。BoNT/A(RYM)对SNAP25无催化活性，对小鼠无毒。用BoNT/A(RYM)免疫可保护小鼠免受攻击，其保护水平与化学灭活的BoNT/A类毒素相似。BoNT/A(RYM)引发了针对毒素轻链和重链成分的免疫反应。中和抗BoNT/A(RYM)血清可阻断原代皮质神经元中的BoNT毒性，并阻断重链与神经节苷脂的结合。BoNT/A(RYM)是一种可行的抗肉毒中毒全类毒素疫苗候选物。
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