Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine.
Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine.
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DOI：
10.15252/msb.20209888
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发表时间：
2020-11
影响因子：
9.9
通讯作者：
Pollard AJ
中科院分区：
文献类型：
--
作者：
O'Connor D;Pinto MV;Sheerin D;Tomic A;Drury RE;Channon-Wells S;Galal U;Dold C;Robinson H;Kerridge S;Plested E;Hughes H;Stockdale L;Sadarangani M;Snape MD;Rollier CS;Levin M;Pollard AJ
脑膜炎奈瑟菌是脑膜炎和败血症的主要病因。MenB疫苗（4CMenB）于2013年1月获得欧洲药品管理局的许可。在这里，我们描述了伴随或不伴随4CMenB的婴儿免疫后的血液转录组和蛋白质组，以深入了解疫苗接种后反应性和免疫原性的分子机制。婴儿在2个月和4个月时随机接受对照免疫接种（PCV13和DTaP - IPV - Hib），接种或不接种4CMenB。分别在接种前、接种后4小时、24小时、3天或7天检测血液基因表达和血浆蛋白。4CMenB疫苗接种与ENTPD7表达增加和4种血浆蛋白浓度增加相关：CRP、G - CSF、IL - 1RA和IL - 6。疫苗接种后发热与参与中性粒细胞募集的SELL表达增加有关。一个解剖疫苗成分的小鼠模型发现，与单独接种4CMenB疫苗相比，伴随方案与基因扰动增加有关，并增强了诸如白细胞介素- 3、- 5和GM - CSF信号通路。最后，我们提出了4CMenB疫苗接种后免疫和发热反应的转录组学预测。一项随机临床试验评估婴儿伴随4CMenB疫苗接种后的转录组学和蛋白质组学特征，与单独接种对照疫苗相比。为理解和预测疫苗的免疫原性和反应原性提供了一个新的框架。
Neisseria meningitidis is a major cause of meningitis and septicaemia. A MenB vaccine (4CMenB) was licensed by the European Medicines Agency in January 2013. Here we describe the blood transcriptome and proteome following infant immunisations with or without concomitant 4CMenB, to gain insight into the molecular mechanisms underlying post‐vaccination reactogenicity and immunogenicity. Infants were randomised to receive control immunisations (PCV13 and DTaP‐IPV‐Hib) with or without 4CMenB at 2 and 4 months of age. Blood gene expression and plasma proteins were measured prior to, then 4 h, 24 h, 3 days or 7 days post‐vaccination. 4CMenB vaccination was associated with increased expression of ENTPD7 and increased concentrations of 4 plasma proteins: CRP, G‐CSF, IL‐1RA and IL‐6. Post‐vaccination fever was associated with increased expression of SELL, involved in neutrophil recruitment. A murine model dissecting the vaccine components found the concomitant regimen to be associated with increased gene perturbation compared with 4CMenB vaccine alone with enhancement of pathways such as interleukin‐3, ‐5 and GM‐CSF signalling. Finally, we present transcriptomic profiles predictive of immunological and febrile responses following 4CMenB vaccine. A randomised clinical trial evaluates transcriptomic and proteomic profiles following infant concomitant 4CMenB vaccination, compared with control vaccines alone. A novel framework is provided for both understanding and predicting vaccine immunogenicity and reactogenicity.
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