Emory Vaccine Center, Emory University, Atlanta, Georgia, USA.
Nat Immunol. 2011 Jul 10;12(8):786-95. doi: 10.1038/ni.2067.
Here we have used a systems biology approach to study innate and adaptive responses to vaccination against influenza in humans during three consecutive influenza seasons. We studied healthy adults vaccinated with trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV). TIV induced higher antibody titers and more plasmablasts than LAIV did. In subjects vaccinated with TIV, early molecular signatures correlated with and could be used to accurately predict later antibody titers in two independent trials. Notably, expression of the kinase CaMKIV at day 3 was inversely correlated with later antibody titers. Vaccination of CaMKIV-deficient mice with TIV induced enhanced antigen-specific antibody titers, which demonstrated an unappreciated role for CaMKIV in the regulation of antibody responses. Thus, systems approaches can be used to predict immunogenicity and provide new mechanistic insights about vaccines.
在这里，我们采用系统生物学的方法，在连续三个流感季节研究了人类对流感疫苗接种的固有和适应性反应。我们研究了健康成年人接种三价灭活流感疫苗（TIV）或减毒活流感疫苗（LAIV）的情况。TIV 诱导的抗体滴度和浆母细胞比 LAIV 更高。在接受 TIV 接种的受试者中，早期的分子特征与后来的抗体滴度相关，并可在两项独立的试验中准确预测。值得注意的是，激酶 CaMKIV 在第 3 天的表达与后期抗体滴度呈负相关。用 TIV 接种 CaMKIV 缺陷型小鼠可诱导增强的抗原特异性抗体滴度，这表明 CaMKIV 在调节抗体反应中具有未被认识的作用。因此，系统方法可用于预测免疫原性，并提供有关疫苗的新的机制见解。
