Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, School of Biological Sciences, The University of Adelaide, SA 5005, Australia.
Institute For Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia.
EBioMedicine. 2017 Apr;18:236-243. doi: 10.1016/j.ebiom.2017.03.002. Epub 2017 Mar 3.
Streptococcus pneumoniae (the pneumococcus) is a major human pathogen, causing a broad spectrum of diseases including otitis media, pneumonia, bacteraemia and meningitis. Here we examined the role of a potential pneumococcal meningitis vaccine antigen, alpha-glycerophosphate oxidase (SpGlpO), in nasopharyngeal colonization. We found that serotype 4 and serotype 6A strains deficient in SpGlpO have significantly reduced capacity to colonize the nasopharynx of mice, and were significantly defective in adherence to human nasopharyngeal carcinoma cells in vitro. We also demonstrate that intranasal immunization with recombinant SpGlpO significantly protects mice against subsequent nasal colonization by wild type serotype 4 and serotype 6A strains. Furthermore, we show that SpGlpO binds strongly to lacto/neolacto/ganglio host glycan structures containing the GlcNAcβ1-3Galβ disaccharide, suggesting that SpGlpO enhances colonization of the nasopharynx through its binding to host glycoconjugates. We propose that SpGlpO is a promising vaccine candidate against pneumococcal carriage, and warrants inclusion in a multi-component protein vaccine formulation that can provide robust, serotype-independent protection against all forms of pneumococcal disease.
肺炎链球菌（肺炎球菌）是一种主要的人类病原体，可引起多种疾病，包括中耳炎、肺炎、菌血症和脑膜炎。在这里，我们研究了一种潜在的肺炎球菌脑膜炎疫苗抗原α-甘油磷酸氧化酶（SpGlpO）在鼻咽定植中的作用。我们发现 SpGlpO 缺失的血清型 4 和 6A 菌株在鼻咽定植的能力显著降低，并且在体外对人鼻咽癌细胞的黏附能力显著缺陷。我们还证明，用重组 SpGlpO 进行鼻腔免疫接种可显著保护小鼠免受随后野生型血清型 4 和 6A 菌株的鼻腔定植。此外，我们表明 SpGlpO 与含有 GlcNAcβ1-3Galβ二糖的乳糖/新乳糖/神经节宿主糖缀合物强烈结合，表明 SpGlpO 通过与宿主糖缀合物结合增强鼻咽定植。我们提出 SpGlpO 是一种有前途的针对肺炎球菌携带的疫苗候选物，值得包含在多组分蛋白质疫苗制剂中，该制剂可以提供针对所有形式肺炎球菌病的强大、非血清型依赖性保护。
