Phase Variation of NadA in Invasive Neisseria meningitidis Isolates Impacts on Coverage Estimates for 4C-MenB, a MenB Vaccine.
Phase Variation of NadA in Invasive Neisseria meningitidis Isolates Impacts on Coverage Estimates for 4C-MenB, a MenB Vaccine.
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DOI：
10.1128/jcm.00204-18
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发表时间：
2018-09
影响因子：
9.4
通讯作者：
Bayliss CD
中科院分区：
文献类型：
--
作者：
Green LR;Lucidarme J;Dave N;Chan H;Clark S;Borrow R;Bayliss CD
重组NADA蛋白是针对B群脑膜炎奈瑟菌(MenB)研制的疫苗4C-MenB(Bexsero)的四种主要保护性抗原之一。脑膜炎球菌抗原分型系统(MATS)被用作评估4C-MenB的侵袭性MenB株复盖率的高通量检测方法。重组NADA蛋白是针对B群脑膜炎奈瑟菌(MenB)研制的疫苗4C-MenB(Bexsero)的四种主要保护性抗原之一。脑膜炎球菌抗原分型系统(MATS)被用作评估4C-MenB的侵袭性MenB株复盖率的高通量检测方法。在存在的情况下，由于位于调节区的5‘taaa重复区域，NADA基因在转录中受到相位可变的变化。对906株携带NADA基因的侵袭性脑膜炎双球菌进行了含有启动子的基因间隔区(IGR)序列和5‘taaa重复数的测定。排除5‘taaa重复，IGR等位基因的数量从82个减少到23个。通过Western blotting和酶联免疫吸附试验(ELISA)，重复次数与NADA表达的低水平和高水平相关。在179株NADA-2/3或NADA-1多肽变异株和480株含NADA-2/3多肽变异株的480株MenW ST-11复合分离株中，83%存在低表达重复数。对于疫苗相容的NADA变异体的菌株，93%的MATS阴性菌株与低表达重复数有关，而MATS相对效力(RP)得分高于阳性杀菌阈值的95%可信区间的菌株中，63%的菌株具有高表达重复数。5‘taaa重复数的分析有可能成为一种快速、高通量的方法来评估4C-MenB的NADA组分的菌株覆盖率。一个关键的应用将是评估脑膜炎球菌病病例的覆盖面，在这些病例中，确认仅通过聚合酶链式反应，而不能应用MATS。
A recombinant NadA protein is one of the four major protective antigens of 4C-MenB (Bexsero), a vaccine developed for serogroup B Neisseria meningitidis (MenB). The meningococcal antigen typing system (MATS) is utilized as a high-throughput assay for assessing the invasive MenB strain coverage of 4C-MenB. A recombinant NadA protein is one of the four major protective antigens of 4C-MenB (Bexsero), a vaccine developed for serogroup B Neisseria meningitidis (MenB). The meningococcal antigen typing system (MATS) is utilized as a high-throughput assay for assessing the invasive MenB strain coverage of 4C-MenB. Where present, the nadA gene is subject to phase-variable changes in transcription due to a 5′TAAA repeat tract located in a regulatory region. The promoter-containing intergenic region (IGR) sequences and 5′TAAA repeat numbers were determined for 906 invasive meningococcal disease isolates possessing the nadA gene. Exclusion of the 5′TAAA repeats reduced the number of IGR alleles from 82 to 23. Repeat numbers were associated with low and high levels of NadA expression by Western blotting and enzyme-linked immunosorbent assay (ELISA). Low-expression repeat numbers were present in 83% of 179 MenB isolates with NadA-2/3 or NadA-1 peptide variants and 68% of 480 MenW ST-11 complex isolates with NadA-2/3 peptide variants. For isolates with vaccine-compatible NadA variants, 93% of MATS-negative isolates were associated with low-expression repeat numbers, whereas 63% of isolates with MATS relative potency (RP) scores above the 95% confidence interval for the positive bactericidal threshold had high-expression repeat numbers. Analysis of 5′TAAA repeat numbers has potential as a rapid, high-throughput method for assessing strain coverage for the NadA component of 4C-MenB. A key application will be assessing coverage in meningococcal disease cases where confirmation is by PCR only and MATS cannot be applied.