Streptococcus pneumoniae remains a deadly disease in small children and the elderly even though conjugate and polysaccharide vaccines based on isolated capsular polysaccharides (CPS) are successful. The most common serotypes that cause infection are used in vaccines around the world, but differences in geographic and demographic serotype distribution compromises protection by leading vaccines. The medicinal chemistry approach to glycoconjugate vaccine development has helped to improve the stability and immunogenicity of synthetic vaccine candidates for several serotypes leading to the induction of higher levels of specific protective antibodies. Here, we show that marketed CPS-based glycoconjugate vaccines can be improved by adding synthetic glycoconjugates representing serotypes that are not covered by existing vaccines. Combination (coformulation) of synthetic glycoconjugates with the licensed vaccines Prevnar13 (13-valent) and Synflorix (10-valent) yields improved 15- and 13-valent conjugate vaccines, respectively, in rabbits. A pentavalent semisynthetic glycoconjugate vaccine containing five serotype antigens (sPCV5) elicits antibodies with strong in vitro opsonophagocytic activity. This study illustrates that synthetic oligosaccharides can be used in coformulation with both isolated polysaccharide glycoconjugates to expand protection from existing vaccines and each other to produce precisely defined multivalent conjugated vaccines.

肺炎链球菌即使基于分离的荚膜多糖（CPS）的结合物和多糖疫苗获得成功，仍然是幼儿和老年人中的致命疾病。导致感染的最常见血清型在世界各地的疫苗中使用，但是地理和人口血清型分布的差异会损害领先疫苗的保护作用。糖缀合物疫苗开发的药物化学方法有助于提高几种血清型的合成疫苗候选物的稳定性和免疫原性，从而诱导更高水平的特异性保护性抗体。在这里，我们表明，可以通过添加代表现有疫苗未涵盖的血清型的合成糖缀合物来改善市售的基于CPS的糖缀合物疫苗。合成糖缀合物与许可疫苗Prevnar13（13价）和Synflorix（10价）的组合（共配制）在兔子中分别产生15和13价缀合物疫苗。包含五个血清型抗原（sPCV5）的五价半合成糖缀合物疫苗可产生具有强大体外调理吞噬活性的抗体。这项研究表明，合成寡糖可与分离的多糖糖缀合物共同配制，以扩大对现有疫苗的保护，并彼此产生精确定义的多价缀合疫苗。包含五个血清型抗原（sPCV5）的五价半合成糖缀合物疫苗可产生具有强大体外调理吞噬活性的抗体。这项研究表明，合成寡糖可与分离的多糖糖缀合物共同配制，以扩大对现有疫苗的保护，并彼此产生精确定义的多价缀合疫苗。包含五个血清型抗原（sPCV5）的五价半合成糖缀合物疫苗可产生具有强大体外调理吞噬活性的抗体。这项研究表明，合成寡糖可与分离的多糖糖缀合物共同配制，以扩大对现有疫苗的保护，并彼此产生精确定义的多价缀合疫苗。