Systems biology of vaccination for seasonal influenza in humans.
Systems biology of vaccination for seasonal influenza in humans.
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DOI：
10.1038/ni.2067
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发表时间：
2011-07-10
影响因子：
30.5
通讯作者：
Pulendran, Bali
中科院分区：
文献类型：
--
作者：
Nakaya, Helder I.;Wrammert, Jens;Lee, Eva K.;Racioppi, Luigi;Marie-Kunze, Stephanie;Haining, W. Nicholas;Means, Anthony R.;Kasturi, Sudhir P.;Khan, Nooruddin;Li, Gui-Mei;McCausland, Megan;Kanchan, Vibhu;Kokko, Kenneth E.;Li, Shuzhao;Elbein, Rivka;Mehta, Aneesh K.;Aderem, Alan;Subbarao, Kanta;Ahmed, Rafi;Pulendran, Bali
我们采用系统生物学方法研究了人类在连续3个流感季节对流感疫苗接种的先天性和适应性反应。健康成人接种灭活（TIV）或减毒活（LAIV）流感疫苗。TIV比LAIV诱导更大的抗体滴度和增强的浆母细胞数量。在两项独立试验中，TIV疫苗接种者的早期分子特征与后来的抗体滴度相关，并能准确预测。有趣的是，在第3天钙/钙调蛋白依赖性激酶IV（CamkIV）的表达与随后的抗体滴度呈负相关。用TIV接种CamkIV −/−小鼠诱导增强的抗原特异性抗体滴度，证明CaMKIV在调节抗体应答中的作用未被认识。因此，系统方法可以预测免疫原性，并揭示有关疫苗的新机制见解。
We used a systems biological approach to study innate and adaptive responses to influenza vaccination in humans, during 3 consecutive influenza seasons. Healthy adults were vaccinated with inactivated (TIV) or live attenuated (LAIV) influenza vaccines. TIV induced greater antibody titers and enhanced numbers of plasmablasts than LAIV. In TIV vaccinees, early molecular signatures correlated with, and accurately predicted, later antibody titers in two independent trials. Interestingly, the expression of Calcium/calmodulin-dependent kinase IV (CamkIV) at day 3 was inversely correlated with later antibody titers. Vaccination of CamkIV −/− mice with TIV induced enhanced antigen-specific antibody titers, demonstrating an unappreciated role for CaMKIV in the regulation of antibody responses. Thus systems approaches can predict immunogenicity, and reveal new mechanistic insights about vaccines.
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