Vaccine Program, Human Health Therapeutics Portfolio, National Research Council, 100, Sussex Drive, National Research Council, Ottawa, ON, K1A 0R6, Canada.
Glycoconj J. 2018 Feb;35(1):53-64. doi: 10.1007/s10719-017-9798-z. Epub 2017 Oct 2.
Dental caries remains a major health issue and the Gram-positive bacterium Streptococcus mutans is considered as the major pathogen causing caries. More recently, S. mutans has been recognised as a cause of endocarditis, ulcerative colitis and fatty acid liver disease along with the likelihood of increased cerebral hemorrhage following a stroke if S. mutans is present systemically. We initiated this study to examine the vaccine candidacy of the serotype specific polysaccharides elaborated by S. mutans. We have confirmed the carbohydrate structures for the serotype specific rhamnan containing polysaccharides from serotypes c, f and k. We have prepared glycoconjugate vaccines using the rhamnan containing polymers from serotypes f and k and immunised mice and rabbits. We consistently obtained a robust immune response to the glycoconjugates with cross-reactivity consistent with the structural similarities of the polymers from the different serotypes. We developed an opsonophagocytic assay which illustrated the ability of the post-immune sera to facilitate opsonophagocytic killing of the homologous and heterologous serotypes at titers consistent with the structural homologies. We conclude that glycoconjugates of the rhamnan polymers of S. mutans are a potential vaccine candidate to target dental caries and other sequelae following the escape of S. mutans from the oral cavity.
龋齿仍然是一个主要的健康问题,而阳性菌变形链球菌被认为是导致龋齿的主要病原体。最近,变形链球菌被认为是心内膜炎、溃疡性结肠炎和脂肪肝的病因之一,如果变形链球菌在全身存在,中风后脑出血的可能性也会增加。我们开始这项研究是为了研究变形链球菌产生的血清型特异性多糖的疫苗候选性。我们已经证实了血清型 c、f 和 k 的具有鼠李糖的多糖的碳水化合物结构。我们已经使用来自血清型 f 和 k 的含有鼠李糖的聚合物制备了糖缀合物疫苗,并对小鼠和兔子进行了免疫接种。我们始终获得了对糖缀合物的强大免疫应答,其交叉反应性与不同血清型聚合物的结构相似性一致。我们开发了一种调理吞噬测定法,该测定法表明,免疫后的血清能够在与结构同源性一致的效价下促进同源和异源血清型的调理吞噬杀伤。我们得出结论,变形链球菌的鼠李糖聚合物糖缀合物是一种有潜力的疫苗候选物,可以针对口腔中变形链球菌逃逸后的龋齿和其他后遗症。