Yiyue Zhang, Xiaotong Wang, Youling Liang, Liangliang Zhang, Jiahao Fan, You Yang
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引用次数: 0
摘要
铜绿假单胞菌是造成医院内感染的主要原因之一,而且对多种抗生素的耐药性越来越强。然而,开发针对耐多药铜绿假单胞菌的新型抗菌剂极其困难。在此,我们开发了一种基于低聚甘露糖醛酸的半合成糖结合疫苗,该疫苗能对粘液和非粘液铜绿假单胞菌菌株的感染产生广泛的保护作用。用弗罗因德佐剂(Freund's adjuvant,FA)配制的定义明确的糖结合疫苗采用了高度保守的抗原,能引起强烈的特异性免疫反应,保护小鼠免受铜绿假单胞菌粘液菌株和非粘液菌株的感染。由此产生的抗体能识别不同的铜绿假单胞菌菌株,并根据菌株表面藻酸盐的表达量,以不同的水平介导对细菌的杀灭。接种糖结合疫苗加 FA 能显著促进肺部和血液对铜绿假单胞菌粘液 PAC1 株的清除,并大大提高小鼠对铜绿假单胞菌非粘液 PAO1 株的存活率。因此,半合成糖轭合物是一种很有前景的疫苗,可针对两种类型的铜绿假单胞菌提供广泛的保护。
A Semisynthetic Oligomannuronic Acid-Based Glycoconjugate Vaccine against Pseudomonas aeruginosa
Pseudomonas aeruginosa 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 P. aeruginosa 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 P. aeruginosa. 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 P. aeruginosa. The resulting antibodies recognized different strains of P. aeruginosa 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 P. aeruginosa and considerably improved the survival rates of mice against the nonmucoid PAO1 strain of P. aeruginosa. Thus, the semisynthetic glycoconjugate is a promising vaccine that may provide broad protection against both types of P. aeruginosa.
期刊介绍:
ACS Central Science publishes significant primary reports on research in chemistry and allied fields where chemical approaches are pivotal. As the first fully open-access journal by the American Chemical Society, it covers compelling and important contributions to the broad chemistry and scientific community. "Central science," a term popularized nearly 40 years ago, emphasizes chemistry's central role in connecting physical and life sciences, and fundamental sciences with applied disciplines like medicine and engineering. The journal focuses on exceptional quality articles, addressing advances in fundamental chemistry and interdisciplinary research.