Orthogonal ligation strategies for making well defined glycoconjugate vaccines

背景：传染病糖结合疫苗代表着一个强大的新兴市场，葛兰素史克最近收购了GlycoVaxyn和诺华疫苗就是明证。利用细菌被膜多糖作为疫苗成分具有广泛的适用性，可以作为预防治疗来保护人和动物的健康。然而，多糖通常不能产生良好的免疫原性，而糖蛋白/糖结合物很难制造出通过监管审查所需的同质形式。在这个项目中，我们将开发新的化学和酶学方法来制备糖结合疫苗，在这种疫苗中，多个不同的多糖表位连接到蛋白质载体上的特定位置。

Background: Glycoconjugate vaccines for infectious diseases represent a strong emerging market, as evidenced by the recent GSK acquisition of Glycovaxyn and Novartis Vaccines. The use of bacterial capsular polysaccharides as vaccine components has general applicability as prophylactic treatments to protect human and animal health. However, glycans generally make poor immunogens and glycoproteins/glycoconjugates are difficult to manufacture in the homogenous form necessary to pass regulatory scrutiny. In this project we will develop new chemical and enzymatic approaches for the preparation of glycoconjugate vaccines in which multiple different polysaccharide epitopes are attached to specific sites on protein carriers.