Department of Chemistry, Michigan State University, 578 S. Shaw Lane, East Lansing, MI 48824, USA.
Department of Chemistry, Michigan State University, 578 S. Shaw Lane, East Lansing, MI 48824, USA; Chemistry Department, Faculty of Science, Benha University, Benha, Qaliobiya 13518, Egypt.
Bioorg Med Chem. 2022 Nov 15;74:117066. doi: 10.1016/j.bmc.2022.117066. Epub 2022 Oct 17.
Pertussis is a highly contagious respiratory disease caused by the Gram-negative bacterial pathogen, Bordetella pertussis. Despite high global vaccination rates, pertussis is resurging worldwide. Here we discuss the development of current pertussis vaccines and their limitations, which highlight the need for new vaccines that can protect against the disease and prevent development of the carrier state, thereby reducing transmission. The lipo-oligosaccharide of Bp is an attractive antigen for vaccine development as the anti-glycan antibodies could have bactericidal activities. The structure of the lipo-oligosaccharide has been determined and its immunological properties analyzed. Strategies enabling the expression, isolation, and bioconjugation have been presented. However, obtaining the saccharide on a large scale with high purity remains one of the main obstacles. Chemical synthesis provides a complementary approach to accessing the carbohydrate epitopes in a pure and structurally well-defined form. The first total synthesis of the non-reducing end pertussis pentasaccharide is discussed. The conjugate of the synthetic glycan with a powerful immunogenic carrier, bacteriophage Qβ, results in high levels and long-lasting anti-glycan IgG antibodies, paving the way for the development of a new generation of anti-pertussis vaccines with high bactericidal activities and biocompatibilities.
百日咳是由革兰氏阴性细菌病原体百日咳博德特氏菌引起的高度传染性呼吸道疾病。尽管全球疫苗接种率很高，但百日咳在全球范围内仍呈卷土重来之势。在这里，我们讨论了当前百日咳疫苗的发展及其局限性，这突出表明需要新的疫苗来预防疾病并防止携带者状态的发展，从而减少传播。Bp 的脂寡糖是疫苗开发的有吸引力的抗原，因为抗聚糖抗体可能具有杀菌活性。已经确定了脂寡糖的结构并分析了其免疫学特性。已经提出了能够实现表达、分离和生物偶联的策略。然而，以高纯度获得大量糖仍然是主要障碍之一。化学合成提供了一种获取纯的和结构上定义良好的碳水化合物表位的互补方法。讨论了非还原端百日咳五糖的首次全合成。该合成聚糖与强大的免疫原性载体噬菌体 Qβ的缀合物导致高水平和持久的抗聚糖 IgG 抗体，为开发具有高杀菌活性和生物相容性的新一代抗百日咳疫苗铺平了道路。
