肉毒毒素B不同功能表位肽疫苗联合免疫的协同保护作用

Synergistic protective effect of peptide vaccines containing different functional epitopes of BoNT/B

肉毒毒素疫苗是防治肉毒中毒发生的重要预防制剂。前期研究发现,针对不同功能表位的中和保护抗体的联合应用具有协同作用。据此推测不同功能表位的多肽疫苗联合免疫也有协同保护作用。为证实该设想,我们结合结构生物学的结果,确立了分别针对BoNT/B上不同功能域的功能表位肽的序列P1(轻链底物结合域)P2(重链蛋白受体结合域)和P3(神经节苷脂结合域),并以此为疫苗,在小鼠体内证明了不同功能表位肽疫苗的联合免疫能够将多肽疫苗的免疫保护效果提高125倍。结果表明,不同功能表位肽疫苗的联合免疫具有显著的协同抵抗BoNT/B攻击的作用。

Botulinum toxin （PONT） vaccine is one of the important means of prevention against botulism. Our previous study found that the combination of different antibodies against different functional epitopes had a synergistic effect against the chal- lenge of BoNT/B. Accordingly, we speculated that the combined immunization with the peptide vaccines containing different functional epitopes may lead to synergistic protective effect. In order to confirmed this idea, we synthesized three peptides con- taining different functional domains respectively, according to the results of structural biology study： P1 （the binding domain of the light chain）, P2 （the receptor binding domain of the heavy chain protein）, and P3 （the ganglioside binding domain）. We found that simultaneous immunization of mice with the three different peptide vaccines resulted in 125-fold increase of the protective effect against BoNT/B. The results showed that the combined peptide vaccines containing different functional epitopes had a significant synergistic protective effect against the challenge of BoNT/B.