Zhang Yiyue, Wang Xiaotong, Liang Youling, Zhang Liangliang, Fan Jiahao, Yang You
Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
ACS Cent Sci. 2024 Jul 10;10(8):1515-1523. doi: 10.1021/acscentsci.4c00387. eCollection 2024 Aug 28.
is one of the leading causes of nosocomial infections and has become increasingly resistant to multiple antibiotics. However, development of novel classes of antibacterial agents against multidrug-resistant is extremely difficult. Herein we develop a semisynthetic oligomannuronic acid-based glycoconjugate vaccine that confers broad protection against infections of both mucoid and nonmucoid strains of . The well-defined glycoconjugate vaccine formulated with Freund's adjuvant (FA) employing a highly conserved antigen elicited a strong and specific immune response and protected mice against both mucoid and nonmucoid strains of . The resulting antibodies recognized different strains of and mediated the opsonic killing of the bacteria at varied levels depending on the amount of alginate expressed on the surface of the strains. Vaccination with the glycoconjugate vaccine plus FA significantly promoted the pulmonary and blood clearance of the mucoid PAC1 strain of and considerably improved the survival rates of mice against the nonmucoid PAO1 strain of . Thus, the semisynthetic glycoconjugate is a promising vaccine that may provide broad protection against both types of .
是医院感染的主要原因之一，并且对多种抗生素的耐药性日益增强。然而，开发针对多重耐药菌的新型抗菌剂极为困难。在此，我们开发了一种基于半合成寡聚甘露糖醛酸的糖缀合物疫苗，它能为黏液型和非黏液型菌株感染提供广泛保护。用弗氏佐剂（FA）配制的明确糖缀合物疫苗采用高度保守的抗原，引发了强烈而特异的免疫反应，并保护小鼠免受黏液型和非黏液型菌株感染。产生的抗体识别不同菌株，并根据菌株表面表达的藻酸盐量在不同水平介导细菌的调理吞噬杀伤作用。用糖缀合物疫苗加FA进行疫苗接种显著促进了黏液型PAC1菌株在肺部和血液中的清除，并显著提高了小鼠抵抗非黏液型PAO1菌株的存活率。因此，这种半合成糖缀合物是一种有前景的疫苗，可能为两种类型的菌株感染提供广泛保护。
