Côté-Cyr Mélanie, Gauthier Laurie, Zottig Ximena, Bourgault Steve, Archambault Denis
Chemistry Department, Université du Québec à Montréal, Montréal, Canada; Quebec Network for Research on Protein Function, Engineering and Applications (PROTEO), Québec, Canada; Department of Biological Sciences, Université du Québec à Montréal, Montréal, Canada; The Swine and Poultry Infectious Diseases Research Centre (CRIPA), Saint-Hyacinthe, Canada.
Quebec Network for Research on Protein Function, Engineering and Applications (PROTEO), Québec, Canada; Department of Biological Sciences, Université du Québec à Montréal, Montréal, Canada; The Swine and Poultry Infectious Diseases Research Centre (CRIPA), Saint-Hyacinthe, Canada.
Vaccine. 2022 Jan 3;40(1):11-17. doi: 10.1016/j.vaccine.2021.11.049. Epub 2021 Nov 26.
Flagellin constitutes a potential adjuvant for vaccines owing to its robust immunostimulatory properties. However, clinical trials have revealed that flagellin derived from Salmonella enterica serovar Typhimurium induces high levels of proinflammatory markers and substantial adverse effects. The flagellin from Bacillus subtilis, Hag, shares high sequence homology with Salmonella FljB within the D0 and D1 domains responsible for TLR5 engagement, while the D2 and D3 domains associated with an off-target immune response are absent. Accordingly, we compared the immunostimulatory and proinflammatory properties of Hag with FljB by harnessing an epitope from the matrix 2 protein (M2e) of the influenza virus. Both flagellins engaged TLR5, with FljB showing a 2.5-fold higher potency than Hag. Mice inoculation showed a robust FljB- or Hag-induced M2e-specific antibody response, with Hag demonstrating a decreased secretion of proinflammatory markers and reduced weight loss. This study revealed that flagellin Hag is a potent immunoadjuvant with reduced proinflammatory properties.
鞭毛蛋白因其强大的免疫刺激特性而成为疫苗的潜在佐剂。然而，临床试验表明，鼠伤寒沙门氏菌的鞭毛蛋白会诱导高水平的促炎标志物并产生严重的不良反应。枯草芽孢杆菌的鞭毛蛋白Hag与沙门氏菌FljB在负责与TLR5结合的D0和D1结构域具有高度序列同源性，而与脱靶免疫反应相关的D2和D3结构域则不存在。因此，我们利用流感病毒基质2蛋白（M2e）的一个表位，比较了Hag与FljB的免疫刺激和促炎特性。两种鞭毛蛋白均与TLR5结合，其中FljB的效力比Hag高2.5倍。小鼠接种显示，FljB或Hag均可诱导强烈的M2e特异性抗体反应，其中Hag表现出促炎标志物分泌减少和体重减轻减轻。这项研究表明，鞭毛蛋白Hag是一种具有降低促炎特性的有效免疫佐剂。
