Hamzabegovic Fahreta, Goll Johannes B, Hooper William F, Frey Sharon, Gelber Casey E, Abate Getahun
1Division of Infectious Diseases, Allergy and Immunology, Saint Louis University, Saint Louis, MO USA.
2EMMES, Rockville, MD USA.
NPJ Vaccines. 2020 Jan 23;5(1):6. doi: 10.1038/s41541-020-0156-y. eCollection 2020.
, the cause of plague, could be weaponized. Unfortunately, development of new vaccines is limited by lack of correlates of protection. We used pre- and post-vaccination sera and peripheral blood mononuclear cells from a flagellin adjuvanted F1/V vaccine trial to evaluate for protective markers. Here, we report for the first time in humans that inverse caspase-3 levels, which are measures of protective antibody, significantly increased by 29% and 75% on days 14 and 28 post-second vaccination, respectively. In addition, there were significant increases in T-cell responses on day 28 post-second vaccination. The strongest positive and negative correlations between protective antibody levels and gene expression signatures were identified for and ENSG00000225107 genes, respectively. Flagellin/F1/V subunit vaccine induced macrophage-protective antibody and significant CD4 T-cell responses. Several genes associated with these responses were identified that could serve as potential correlates of protection.
鼠疫杆菌，即鼠疫的病原体，可能被武器化。不幸的是，新疫苗的研发受到缺乏保护相关性指标的限制。我们利用来自鞭毛蛋白佐剂F1/V疫苗试验的接种前和接种后血清以及外周血单核细胞来评估保护标志物。在此，我们首次在人类中报告，作为保护性抗体指标的反向半胱天冬酶-3水平在第二次接种后第14天和第28天分别显著增加了29%和75%。此外，在第二次接种后第28天T细胞反应显著增加。分别针对 和ENSG00000225107基因确定了保护性抗体水平与基因表达特征之间最强的正相关和负相关。鞭毛蛋白/F1/V亚单位疫苗诱导了巨噬细胞保护性抗体和显著的CD4 T细胞反应。确定了几个与这些反应相关的基因，它们可作为潜在的保护相关性指标。
