Clustered intergenic region sequences as predictors of factor H Binding Protein expression patterns and for assessing Neisseria meningitidis strain coverage by meningococcal vaccines.
Clustered intergenic region sequences as predictors of factor H Binding Protein expression patterns and for assessing Neisseria meningitidis strain coverage by meningococcal vaccines.
复制标题
DOI：
10.1371/journal.pone.0197186
复制
发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Bayliss CD
中科院分区：
文献类型：
--
作者：
Cayrou C;Akinduko AA;Mirkes EM;Lucidarme J;Clark SA;Green LR;Cooper HJ;Morrissey J;Borrow R;Bayliss CD
因子H结合蛋白（fHbp）是4C-MenB（Bexsero®）和Trumenba®（两种血清群B脑膜炎球菌疫苗）中的主要保护性抗原，其中表达水平是保护的决定因素。对含有启动子的基因间区（IGR）序列的检查表明，9个fHbp IGR等位基因覆盖了1,032个具有变体1 fHbp等位基因的侵袭性脑膜炎球菌菌株的92%。通过定量逆转录聚合酶链反应（qRT PCR）确定了79个脑膜炎球菌分离株的fHbp相对表达值，涵盖10个IGR等位基因。通过线性回归推导IGR序列的表达簇鉴定了具有5个核苷酸和1个插入的5个表达簇，其显示与表达水平差异的统计学关联。通过脑膜炎球菌抗原分型方案（夹心ELISA）检查的273株分离株的序列分析发现，覆盖率取决于IGR表达簇和疫苗肽同源性组合。特异性fHbp肽-IGR表达簇组合被指定为4C-MenB覆盖率的“风险”，并在仅通过PCR确认的多发性侵袭性脑膜炎球菌疾病病例中检测到，并发生在部分接种疫苗的婴儿中。我们的结论是，基于序列的分析IGR序列是信息评估蛋白质的表达，并具有实用性的菌株覆盖率的蛋白质为基础的疫苗的文化独立的评估。
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.
登录
查看更多内容
DOI：
10.1084/jem.20021911
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Masignani V;Comanducci M;Giuliani MM;Bambini S;Adu-Bobie J;Arico B;Brunelli B;Pieri A;Santini L;Savino S;Serruto D;Litt D;Kroll S;Welsch JA;Granoff DM;Rappuoli R;Pizza M
通讯作者：
Pizza M
影响因子：
3.7
作者：
Lemee, Ludovic;Hong, Eva;Taha, Muhamed-Kheir
通讯作者：
Taha, Muhamed-Kheir
DOI：
10.1073/pnas.1521142113
发表时间：
2016-03-08
影响因子：
11.1
作者：
Biagini, Massimiliano;Spinsanti, Marco;Masignani, Vega
通讯作者：
Masignani, Vega
影响因子：
56.3
作者：
Parikh, Sydel R.;Newbold, Lynne;Borrow, Ray
通讯作者：
Borrow, Ray
DOI：
10.1073/pnas.1013758107
发表时间：
2010-11-09
影响因子：
11.1
作者：
Donnelly, John;Medini, Duccio;Giuliani, Marzia Monica
通讯作者：
Giuliani, Marzia Monica