Beijing Institute of Biotechnology, Beijing 100071, China; Pharmaceutical College, Henan University, Kaifeng 475001, China.
Beijing Institute of Biotechnology, Beijing 100071, China.
Vaccine. 2020 Mar 23;38(14):2978-2983. doi: 10.1016/j.vaccine.2020.02.060. Epub 2020 Feb 26.
Botulinum neurotoxins (BoNTs) are highly toxic proteins that mediate their effects by binding to neuronal receptors and block the neutralizing ability of therapeutic antibodies. Vaccination is currently the most effective strategy to prevent botulism. In this study, a series of recombinant functional domain antigens of BoNT/A were prepared and identified, and their immunoprotective efficacies were explored and compared. Our results showed that all antigens produced strong humoral immune responses, although their protective effects against the toxin were different. Only the Hc and HN-L antigens produced strong protective effects and afforded complete immunoprotection. In addition, the combined vaccine groups showed that there was no synergistic effect on immune responses after antigen combination, suggesting that the integrity of the toxin antigen or domain is crucial to the immune effects. Studies of the dose-dependent immunoprotective effects further confirmed that the Hc domain antigen afforded more effective protective potency than the HN-L antigen, equivalent to the immune effect of the full-length toxin (Hc + HN-L combination group). Overall, our results demonstrated that the Hc domain elicited a strong protective immune response and also provided basic data and theoretical support for the development of Hc-based BoNT/A subunit vaccine. Therefore, the receptor binding domain Hc is implicated as a promising target antigen of the BoNT/A recombinant subunit vaccine as an alternative to the toxoid vaccine.
肉毒神经毒素（BoNTs）是高度毒性的蛋白质，通过与神经元受体结合来发挥作用，并阻止治疗性抗体的中和能力。疫苗接种是预防肉毒中毒的最有效策略。在这项研究中，制备并鉴定了一系列 BoNT/A 的重组功能结构域抗原，并探索和比较了它们的免疫保护效力。我们的结果表明，所有抗原都产生了强烈的体液免疫反应，尽管它们对毒素的保护效果不同。只有 Hc 和 HN-L 抗原产生了强烈的保护作用，并提供了完全的免疫保护。此外，联合疫苗组表明，抗原组合后免疫反应没有协同作用，这表明毒素抗原或结构域的完整性对于免疫效果至关重要。对剂量依赖性免疫保护效果的研究进一步证实，Hc 结构域抗原比 HN-L 抗原提供了更有效的保护效力，相当于全长毒素的免疫效果（Hc+HN-L 联合组）。总的来说，我们的结果表明 Hc 结构域引发了强烈的保护性免疫反应，为基于 Hc 的 BoNT/A 亚单位疫苗的开发提供了基本数据和理论支持。因此，受体结合结构域 Hc 被认为是 BoNT/A 重组亚单位疫苗的有前途的靶抗原，可替代类毒素疫苗。
