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Optimization of the Synthesis and Conjugation of the Methyl Rhamnan Tip of Pseudomonas aeruginosa A-Band Polysaccharide and Immunogenicity Evaluation for the Continued Development of a Potential Glycoconjugate Vaccine
ACS Infectious Diseases ( IF 5.3 ) Pub Date : 2024-03-06 , DOI: 10.1021/acsinfecdis.4c00049
Mohammad P. Jamshidi 1 , Chantelle Cairns 1 , Nam Huan Khieu 1 , Kenneth Chan 1 , Frank St. Michael 1 , Andrew Cox 1 , Janelle Sauvageau 1
Affiliation  

Pseudomonas aeruginosa is an antimicrobial-resistant bacterium that has no vaccine approved for human use. Additionally, it has been identified by the World Health Organization as a priority pathogen for novel vaccines and therapeutic development. We previously developed a synthetic mimic of the A-band polysaccharide tip that showed promise in terms of immunogenicity for use as a glycoconjugate vaccine. In this current manuscript, we improve upon the previous work to continue the development of this glycoconjugate vaccine. Herein, we report a higher-yielding synthesis of mimics containing a handle and a spacer that improved conjugation efficiency, resulting in better carbohydrate-to-protein ratios and also good immunogenicity of these conjugates in mice and rabbits. The data suggested that perhaps only a tetrasaccharide was required to induce an immune response capable of recognizing whole cells of P. aeruginosa.

中文翻译:

铜绿假单胞菌 A 带多糖甲基鼠李聚糖尖端的合成和结合优化及免疫原性评价,以继续开发潜在的糖结合疫苗

铜绿假单胞菌是一种耐药细菌,目前还没有批准用于人类使用的疫苗。此外,世界卫生组织已将其确定为新型疫苗和治疗开发的优先病原体。我们之前开发了 A 带多糖尖端的合成模拟物,其在免疫原性方面显示出用作糖复合物疫苗的希望。在当前的手稿中,我们改进了之前的工作,以继续开发这种复合糖疫苗。在此,我们报道了含有手柄和间隔基的模拟物的高产合成,该模拟物提高了缀合效率,从而导致更好的碳水化合物与蛋白质比率以及这些缀合物在小鼠和兔子中的良好免疫原性。数据表明,也许只需要四糖就可以诱导能够识别铜绿假单胞菌整个细胞的免疫反应。
更新日期:2024-03-06
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