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首页> 美国卫生研究院文献>PLoS Clinical Trials >Clustered intergenic region sequences as predictors of factor H Binding Protein expression patterns and for assessing Neisseria meningitidis strain coverage by meningococcal vaccines
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Clustered intergenic region sequences as predictors of factor H Binding Protein expression patterns and for assessing Neisseria meningitidis strain coverage by meningococcal vaccines

机译：聚集的基因间区域序列可作为因子H结合蛋白表达模式的预测因子，并用于评估脑膜炎球菌疫苗对脑膜炎奈瑟氏球菌的覆盖率

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Factor H binding protein (fHbp) is a major protective antigen in 4C-MenB (Bexsero®) and Trumenba®, two serogroup B meningococcal vaccines, wherein expression level is a determinant of protection. Examination of promoter-containing intergenic region (IGR) sequences indicated that nine fHbp IGR alleles covered 92% of 1,032 invasive meningococcal strains with variant 1 fHbp alleles. Relative expression values for fHbp were determined for 79 meningococcal isolates covering ten IGR alleles by quantitative reverse transcriptase polymerase chain reaction (qRT PCR). Derivation of expression clusters of IGR sequences by linear regression identified five expression clusters with five nucleotides and one insertion showing statistically associations with differences in expression level. Sequence analysis of 273 isolates examined by the Meningococcal Antigen Typing Scheme, a sandwich ELISA, found that coverage depended on the IGR expression cluster and vaccine peptide homology combination. Specific fHbp peptide-IGR expression cluster combinations were designated as ‘at risk’ for coverage by 4C-MenB and were detected in multiple invasive meningococcal disease cases confirmed by PCR alone and occurring in partially-vaccinated infants. We conclude that sequence-based analysis of IGR sequences is informative for assessing protein expression and has utility for culture-independent assessments of strain coverage by protein-based vaccines.
机译：H因子结合蛋白（fHbp）是4C-MenB（Bexsero ®）和Trumenba ®（两种血清B型脑膜炎球菌疫苗）中的主要保护性抗原，其中表达水平是决定因素保护。包含启动子的基因间区域（IGR）序列的检查表明，九个fHbp IGR等位基因覆盖了具有1个fHbp等位基因的1,032例侵袭性脑膜炎球菌菌株的92％。通过定量逆转录酶聚合酶链反应（qRT PCR）确定了涵盖10个IGR等位基因的79个脑膜炎球菌分离株的fHbp相对表达值。通过线性回归推导IGR序列的表达簇，鉴定出五个具有五个核苷酸和一个插入的表达簇，其在统计上与表达水平的差异相关。通过脑膜炎球菌抗原分型计划（夹心ELISA）检查的273个分离株的序列分析发现，覆盖范围取决于IGR表达簇和疫苗肽同源性组合。特定的fHbp肽-IGR表达簇组合被指定为4C-MenB覆盖的“风险”，并在仅通过PCR确认并在部分疫苗接种的婴儿中发生的多发性侵袭性脑膜炎球菌病例中检测到。我们得出的结论是，基于序列的IGR序列分析有助于评估蛋白质表达，并且可用于基于蛋白质的疫苗对菌株覆盖率的独立于培养的评估。

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