a Chemistry of Biomolecules Unit, Department of Structural Biology and Chemistry , Institut Pasteur, UMR3523, CNRS , Paris , France.
b Université Paris Descartes , Paris , France.
Hum Vaccin Immunother. 2019;15(6):1338-1356. doi: 10.1080/21645515.2019.1606972.
are gram-negative bacteria that cause severe diarrhea and dysentery, with a high level of antimicrobial resistance. Disease-induced protection against reinfection in -endemic areas provides convincing evidence on the feasibility of a vaccine and on the importance of lipopolysaccharides as targets of the host humoral protective immune response against disease. This article provides an overview of the original and current strategies toward the development of a glycan-protein conjugate vaccine that would cover the most commonly detected strains. Going beyond pioneering "lattice"-type polysaccharide-protein conjugates, progress, and challenges are addressed with focus on promising alternatives, which have reached phases I and II clinical trial. Glycoengineered bioconjugates and "sun"-type conjugates featuring well-defined synthetic carbohydrate antigens are discussed with insights on the molecular parameters governing the rational design of a cost-effective glycoconjugate vaccine efficacious in preventing diseases caused by in the most at risk populations, young children living in endemic areas.
这些细菌是革兰氏阴性菌，会导致严重的腹泻和痢疾，并且具有很高的抗药性。在地方性流行地区，疾病引起的再感染保护为疫苗的可行性以及脂多糖作为宿主体液保护性免疫反应针对疾病的靶标提供了令人信服的证据。本文概述了开发糖蛋白缀合物疫苗的原始和当前策略，该疫苗将涵盖最常见的检测菌株。除了开创性的“晶格”型多糖-蛋白缀合物外，还解决了进展和挑战的问题，并重点介绍了已进入 I 期和 II 期临床试验的有前途的替代方案。本文还讨论了经过糖基工程改造的生物缀合物和“太阳”型缀合物，这些缀合物具有明确的合成碳水化合物抗原，并深入了解了控制成本效益糖缀合物疫苗设计的分子参数，该疫苗在预防最易受感染的人群（生活在地方性流行地区的幼儿）中由 引起的疾病方面非常有效。
