In 2009, a novel influenza vaccine was distributed worldwide to combat the H1N1 influenza “swine flu” pandemic. However, antibodies induced by the vaccine display differences in their specificity and cross-reactivity dependent on pre-existing immunity. Here, we present a computational model that can capture the effect of pre-existing immunity on influenza vaccine responses. The model predicts the region of the virus hemagglutinin (HA) protein targeted by antibodies after vaccination as well as the level of cross-reactivity induced by the vaccine. We tested our model by simulating a scenario similar to the 2009 pandemic vaccine and compared the results to antibody binding data obtained from human subjects vaccinated with the monovalent 2009 H1N1 influenza vaccine. We found that both specificity and cross-reactivity of the antibodies induced by the 2009 H1N1 influenza HA protein were affected by the viral strain the individual was originally exposed. Specifically, the level of antigenic relatedness between the original exposure HA antigen and the 2009 HA protein affected antigenic-site immunodominance. Moreover, antibody cross-reactivity was increased when the individual’s pre-existing immunity was specific to an HA protein antigenically distinct from the 2009 pandemic strain. Comparison of simulation data with antibody binding data from human serum samples demonstrated qualitative and quantitative similarities between the model and real-life immune responses to the 2009 vaccine. We provide a novel method to evaluate expected outcomes in antibody specificity and cross-reactivity after influenza vaccination in individuals with different influenza HA antigen exposure histories. The model produced similar outcomes as what has been previously reported in humans after receiving the 2009 influenza pandemic vaccine. Our results suggest that differences in cross-reactivity after influenza vaccination should be expected in individuals with different exposure histories.

中文翻译：

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将基于序列的抗原距离计算实施到免疫形状空间模型中。

2009 年，一种新型流感疫苗在全球范围内分发，以对抗 H1N1 流感“猪流感”大流行。然而，疫苗诱导的抗体在其特异性和交叉反应性方面表现出差异，这取决于预先存在的免疫力。在这里，我们提出了一个计算模型，可以捕捉预先存在的免疫力对流感疫苗反应的影响。该模型预测疫苗接种后抗体靶向的病毒血凝素 (HA) 蛋白区域以及疫苗诱导的交叉反应水平。我们通过模拟类似于 2009 年大流行疫苗的场景来测试我们的模型，并将结果与​​从接种了单价 2009 H1N1 流感疫苗的人类受试者获得的抗体结合数据进行比较。我们发现由 2009 H1N1 流感 HA 蛋白诱导的抗体的特异性和交叉反应性都受到个体最初接触的病毒株的影响。具体而言，原始暴露的 HA 抗原与 2009 年 HA 蛋白之间的抗原相关性水平影响了抗原位点免疫优势。此外，当个体预先存在的免疫对抗原性不同于 2009 年大流行毒株的 HA 蛋白具有特异性时，抗体交叉反应性会增加。将模拟数据与来自人血清样本的抗体结合数据进行比较，证明了模型与对 2009 年疫苗的真实免疫反应之间的定性和定量相似性。我们提供了一种新方法来评估具有不同流感 HA 抗原暴露史的个体接种流感疫苗后抗体特异性和交叉反应性的预期结果。该模型产生的结果与之前在人类接种 2009 年流感大流行疫苗后报告的结果相似。我们的结果表明，在具有不同暴露史的个体中，应该预期流感疫苗接种后交叉反应性的差异。