Laboratory of Immunology and Epigenetics, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
Front Cell Infect Microbiol. 2023 Jul 14;13:1200789. doi: 10.3389/fcimb.2023.1200789. eCollection 2023.
Trained immunity is the enhanced innate immune response resulting from exposure to pathogens or vaccines against an unrelated pathogen stimulus. Certain vaccines induce a memory like response in monocytes and NK cells, leading to modulation in cytokine production, metabolic changes, and modifications in histone patterns. Here, we hypothesized that vaccination against SARS-CoV-2 could induce the training of monocytes in addition to stimulating the adaptive immune response.
Therefore, we aimed to investigate the immunophenotyping, cytokine and metabolic profile of monocytes from individuals who were completely immunized with two doses of inactivated COVID-19 vaccine or non-replicating viral vector vaccine. Subsequently, we investigated the epigenetic mechanisms underlying monocyte immune training. As a model of inflammatorychallenge, to understand if the monocytes were trained by vaccination and how they were trained, cells were stimulated with the endotoxin LPS, an unrelated stimulus that would provoke the effects of training.
When challenged monocytes from vaccinated individuals produced less TNF-α and those who received inactivated vaccine produced less IL-6, whereas vaccination with non-replicating viral vector vaccine induced more IL-10. Inactivated vaccine increased classical monocyte frequency, and both groups showed higher CD163 expression, a hallmark of trained immunity. We observed increased expression of genes involved in glycolysis and reduced IRG1 expression in vaccinated subjects, a gene associated with the tolerance phenotype in monocytes. We observed that both vaccines reduced the chromatin accessibility of genes associated with the inflammatory response, the inactivated COVID-19 vaccine trained monocytes to a regulatory phenotype mediated by histone modifications in the and genes, while the non-replicating viral vector COVID-19 vaccine trained monocytes to a regulatory phenotype, mediated by histone modifications in the , and genes.
Our findings support the recognized importance of adopting vaccination against SARS CoV-2, which has been shown to be effective in enhancing the adaptive immune response against the virus and reducing mortality and morbidity rates. Here, we provide evidence that vaccination also modulates the innate immune response by controlling the detrimental inflammatory response to unrelated pathogen stimulation.
训练有素的免疫是指由于暴露于病原体或针对无关病原体刺激的疫苗而导致的增强的先天免疫反应。某些疫苗会在单核细胞和 NK 细胞中引起类似记忆的反应，导致细胞因子产生、代谢变化和组蛋白模式的改变。在这里，我们假设针对 SARS-CoV-2 的疫苗接种除了刺激适应性免疫反应外，还可以诱导单核细胞的训练。
因此，我们旨在研究完全接种两剂灭活 COVID-19 疫苗或非复制病毒载体疫苗的个体的单核细胞的免疫表型、细胞因子和代谢谱。随后，我们研究了单核细胞免疫训练的表观遗传机制。作为炎症挑战的模型，为了了解单核细胞是否通过疫苗接种而被训练以及它们是如何被训练的，用内毒素 LPS 刺激细胞，这是一种无关的刺激物，会引发训练的效果。
当受到挑战时，接种疫苗的个体的单核细胞产生的 TNF-α 较少，而接种灭活疫苗的个体产生的 IL-6 较少，而接种非复制病毒载体疫苗会诱导更多的 IL-10。灭活疫苗增加了经典单核细胞的频率，并且两组都显示出更高的 CD163 表达，这是训练有素的免疫的标志。我们观察到接种疫苗的个体中与糖酵解相关的基因表达增加，而 IRG1 表达减少，IRG1 是单核细胞耐受表型的一个标志。我们观察到两种疫苗都降低了与炎症反应相关的基因的染色质可及性，灭活 COVID-19 疫苗通过修饰 和 基因中的组蛋白将单核细胞训练为调节表型，而非复制病毒载体 COVID-19 疫苗通过修饰 、 和 基因中的组蛋白将单核细胞训练为调节表型。
我们的发现支持接种 SARS CoV-2 疫苗的重要性，接种疫苗已被证明可有效增强针对该病毒的适应性免疫反应，并降低死亡率和发病率。在这里，我们提供的证据表明，疫苗接种还通过控制对无关病原体刺激的有害炎症反应来调节先天免疫反应。
