Department of Immunology, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia.
Int J Mol Sci. 2022 Jul 26;23(15):8234. doi: 10.3390/ijms23158234.
Vaccination protects against COVID-19 via the spike protein receptor-binding domain (RBD)-specific antibody formation, but it also affects the innate immunity. The effects of specific antibody induction on neutrophils that can cause severe respiratory inflammation are important, though not completely investigated. In the present study, using a mouse model mimicking SARS-CoV-2 virus particle inhalation, we investigated neutrophil phenotype and activity alterations in the presence of RBD-specific antibodies. Mice were immunized with RBD and a week after a strong antibody response establishment received 100 nm particles in the RBD solution. Control mice received injections of a phosphate buffer instead of RBD. We show that the application of 100 nm particles in the RBD solution elevates neutrophil recruitment to the blood and the airways of RBD-immunized mice rather than in control mice. Analysis of bone marrow cells of mice with induced RBD-specific antibodies revealed the increased population of CXCR2CD101 neutrophils. These neutrophils did not demonstrate an enhanced ability of neutrophil extracellular traps (NETs) formation compared to the neutrophils from control mice. Thus, the induction of RBD-specific antibodies stimulates the activation of mature neutrophils that react to RBD-coated particles without triggering excessive inflammation.
疫苗通过刺突蛋白受体结合域(RBD)特异性抗体的形成来预防 COVID-19,但它也会影响固有免疫。诱导特异性抗体对可能引起严重呼吸道炎症的中性粒细胞的影响很重要,但尚未完全研究。在本研究中,我们使用模拟 SARS-CoV-2 病毒颗粒吸入的小鼠模型,研究了存在 RBD 特异性抗体时中性粒细胞表型和活性的改变。用 RBD 免疫小鼠,一周后建立强烈的抗体反应,然后在 RBD 溶液中接受 100nm 颗粒。对照组小鼠接受磷酸盐缓冲液而不是 RBD 的注射。我们表明,在 RBD 溶液中应用 100nm 颗粒会增加 RBD 免疫小鼠而不是对照组小鼠血液和气道中中性粒细胞的募集。对诱导产生 RBD 特异性抗体的小鼠骨髓细胞的分析显示,CXCR2CD101 中性粒细胞的数量增加。与对照组小鼠的中性粒细胞相比,这些中性粒细胞形成中性粒细胞胞外诱捕网(NETs)的能力没有增强。因此,RBD 特异性抗体的诱导刺激成熟中性粒细胞的激活,这些中性粒细胞对 RBD 包被的颗粒作出反应而不会引发过度炎症。