School of Chemical and Physical Sciences, Victoria University of Wellington, PO Box 600, Wellington, New Zealand; Centre for Biodiscovery, Victoria University of Wellington, PO Box 600, Wellington, New Zealand.
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
Bioorg Chem. 2021 May;110:104747. doi: 10.1016/j.bioorg.2021.104747. Epub 2021 Mar 4.
Many studies have investigated how trehalose glycolipid structures can be modified to improve their Macrophage inducible C-type lectin (Mincle)-mediated adjuvanticity. However, in all instances, the ester-linkage of α,ά-trehalose to the lipid of choice remained. We investigated how changing this ester-linkage to an amide influences Mincle signalling and agonist activity and demonstrated that Mincle tolerates this functional group change. In in vivo vaccination studies in murine and ovine model systems, using OVA or Mannheimia haemolytica and Mycoplasma ovipneumoniae as vaccine antigens, respectively, it was demonstrated that a representative trehalose diamide glycolipid was able to enhance antibody-specific immune responses. Notably, IgG titres against M. ovipneumoniae were significantly greater when using trehalose dibehenamide (A-TDB) compared to trehalose dibehenate (TDB). This is particularly important as infection with M. ovipneumoniae predisposes sheep to pneumonia.
许多研究都探讨了如何修饰海藻糖糖脂结构以提高其巨噬细胞诱导 C 型凝集素 (Mincle) 介导的佐剂活性。然而，在所有情况下，都保持了 α,α-海藻糖与所选脂质的酯键连接。我们研究了将这种酯键改变为酰胺如何影响 Mincle 信号传导和激动剂活性，并证明 Mincle 可以耐受这种功能基团的变化。在使用 OVA 或 Mannheimia haemolytica 和 Mycoplasma ovipneumoniae 作为疫苗抗原的小鼠和绵羊模型系统的体内疫苗接种研究中，分别表明代表性的海藻糖二酰胺糖脂能够增强针对抗体的免疫反应。值得注意的是，与海藻糖二庚酸酯 (TDB) 相比，使用海藻糖二正癸酰胺 (A-TDB) 时针对 M. ovipneumoniae 的 IgG 滴度显著更高。这一点尤其重要，因为感染 M. ovipneumoniae 会使绵羊易患肺炎。
