PDF(Pubmed)
Abstract：
The effectiveness of coronavirus disease 2019 (COVID-19) vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain rapidly wanes over time. Growing evidence from epidemiological studies suggests that influenza vaccination is associated with a reduction in the risk of SARS-CoV-2 infection and COVID-19 severity. However, the underlying mechanisms remain elusive. Here, we investigate the cross-reactive immune responses of influenza vaccination to SARS-CoV-2 spike protein peptides based on in vitro study. Our data indicate enhanced activation-induced-marker (AIM) expression on CD4+ T cells in influenza-vaccination (IV)-treated peripheral blood mononuclear cells (PBMCs) upon stimulation with spike-protein-peptide pools. The fractions of other immune cell subtypes, including CD8+ T cells, monocytes, NK cells, and antigen-presenting cells, were not changed between IV-treated and control PBMCs following ex vivo spike-protein-peptide stimulation. However, the classical antiviral (IFN-γ) and anti-inflammatory (IL-1RA) cytokine responses to spike-protein-peptide stimulation were still enhanced in PBMCs from both IV-immunized adult and aged mice. Decreased expression of proinflammatory IL-1β, IL-12p40, and TNF-α is associated with inhibited levels of histone acetylation in PBMCs from IV-treated mice. Remarkably, prior immunity to SARS-CoV-2 does not result in modification of histone acetylation or hemagglutinin-protein-induced cytokine responses. This response is antibody-independent but can be mediated by manipulating the histone acetylation of PBMCs. These data experimentally support that influenza vaccination could induce modification of histone acetylation in immune cells and reveal the existence of potential cross-reactive immunity to SARS-CoV-2 antigens, which may provide insights for the adjuvant of influenza vaccine to limit COVID-19-related inflammatory responses.
摘要：
冠状病毒病2019（COVID-19）疫苗对严重急性呼吸道综合症冠状病毒2（SARS-CoV-2）株的有效性随着时间的推移而迅速减弱。来自流行病学研究的越来越多的证据表明，流感疫苗接种与降低SARS-CoV-2感染和COVID-19严重程度的风险有关。然而,潜在的机制仍然难以捉摸。这里,我们基于体外研究，研究了流感疫苗接种对SARS-CoV-2刺突蛋白肽的交叉反应性免疫反应。我们的数据表明，在用刺突蛋白肽池刺激后，流感疫苗接种（IV）处理的外周血单核细胞（PBMC）中CD4T细胞上的活化诱导标记（AIM）表达增强。其他免疫细胞亚型的部分，包括CD8+T细胞，单核细胞,NK细胞,和抗原呈递细胞，在离体刺突蛋白-肽刺激后，IV处理和对照PBMC之间没有变化。然而,在IV免疫成年和老年小鼠的PBMC中,经典的抗病毒(IFN-γ)和抗炎(IL-1RA)细胞因子对刺突蛋白-肽刺激的反应仍得到增强.促炎性IL-1β表达降低,IL-12p40和TNF-α与IV处理小鼠的PBMC中组蛋白乙酰化的抑制水平相关。值得注意的是,对SARS-CoV-2的先前免疫不会导致组蛋白乙酰化或血凝素蛋白诱导的细胞因子反应的改变。该应答是抗体非依赖性的,但可以通过操纵PBMC的组蛋白乙酰化来介导。这些数据在实验上支持流感疫苗接种可以诱导免疫细胞中组蛋白乙酰化的修饰，并揭示了对SARS-CoV-2抗原的潜在交叉反应性免疫的存在。这可能为流感疫苗的佐剂限制COVID-19相关的炎症反应提供见解。
