Abstract：
Published work has shown that glycoconjugate vaccines, based on truncated detoxified lipopolysaccharides from Moraxella catarrhalis attached through their reducing end to a carrier protein, gave good protection for all three serotypes A, B, and C in mice immunisation experiments. The (from the non-reducing end) truncated LPS structures were obtained from bacterial glycosyl transferase knock-out mutants and contained the de-esterified Lipid A, two Kdo residues and five glucose moieties. This work describes the chemical synthesis of the same outer Moraxella LPS structures, spacer-equipped and further truncated from the reducing end, i.e., without the Lipid A part and containing four or five glucose moieties or four glucose moieties and one Kdo residue, and their subsequent conjugation to a carrier protein via a five‑carbon bifunctional spacer to form glycoconjugates. Immunisation experiments both in mice and rabbits of these gave a good antibody response, being 2-7 times that of pre-immune sera. However, the sera produced only recognized the immunizing glycan immunogens and failed to bind to native LPS or whole bacterial cells. Comparative molecular modelling of three alternative antigens shows that an additional (2 → 4)-linked Kdo residue, not present in the synthetic structures, has a significant impact on the shape and volume of the molecule, with implications for antigen binding and cross-reactivity.
摘要：
已发表的工作表明，糖缀合物疫苗，基于来自粘膜炎莫拉氏菌的截短的解毒脂多糖，通过其还原端附着到载体蛋白，对所有三种血清型A都有很好的保护作用，B,和C在小鼠免疫实验中。（来自非还原端）截短的LPS结构是从细菌糖基转移酶敲除突变体中获得的，并含有去酯化的脂质A，两个Kdo残基和五个葡萄糖部分。这项工作描述了相同的外部莫拉氏菌LPS结构的化学合成，配备垫片，并从减少端进一步截断，即，没有脂质A部分，并且含有四个或五个葡萄糖部分或四个葡萄糖部分和一个Kdo残基，以及它们随后通过五碳双功能间隔子与载体蛋白缀合以形成糖缀合物。这些小鼠和兔子的免疫实验都产生了良好的抗体反应，是免疫前血清的2-7倍。然而,所产生的血清仅识别免疫化聚糖免疫原并且不能与天然LPS或整个细菌细胞结合。三种替代抗原的比较分子模型表明，额外的（2→4）连接的Kdo残基，不存在于合成结构中，对分子的形状和体积有重大影响，与抗原结合和交叉反应性有关。
