PDF(Pubmed)
Abstract：
SARS-CoV-2 initially infects cells in the nasopharynx and oral cavity. The immune system at these mucosal sites plays a crucial role in minimizing viral transmission and infection. To develop new strategies for preventing SARS-CoV-2 infection, this study aimed to identify proteins that protect against viral infection in saliva. We collected 551 saliva samples from 290 healthcare workers who had tested positive for COVID-19, before vaccination, between June and December 2020. The samples were categorized based on their ability to block or enhance infection using in vitro assays. Mass spectrometry and enzyme-linked immunosorbent assay experiments were used to identify and measure the abundance of proteins that specifically bind to SARS-CoV-2 antigens. Immunoglobulin (Ig)A specific to SARS-CoV-2 antigens was detectable in over 83% of the convalescent saliva samples. We found that concentrations of anti-receptor-binding domain IgA >500 pg/µg total protein in saliva correlate with reduced viral infectivity in vitro. However, there is a dissociation between the salivary IgA response to SARS-CoV-2, and systemic IgG titers in convalescent COVID-19 patients. Then, using an innovative technique known as spike-baited mass spectrometry, we identified novel spike-binding proteins in saliva, most notably vimentin, which correlated with increased viral infectivity in vitro and could serve as a therapeutic target against COVID-19.
摘要：
SARS-CoV-2最初感染鼻咽和口腔中的细胞。这些粘膜部位的免疫系统在减少病毒传播和感染方面起着至关重要的作用。制定预防SARS-CoV-2感染的新策略,这项研究旨在鉴定唾液中预防病毒感染的蛋白质。我们收集了290名医护人员的551份唾液样本，这些人在接种疫苗前对COVID-19检测呈阳性，2020年6月至12月。使用体外测定,基于样品阻断或增强感染的能力对样品进行分类。质谱和ELISA实验用于鉴定和测量特异性结合SARS-CoV-2抗原的蛋白质的丰度。在超过83％的恢复期唾液样品中可检测到对SARS-CoV-2抗原具有特异性的IgA。我们发现唾液中抗RBDIgA的浓度>500μg/μg总蛋白与体外病毒感染性降低相关。然而,恢复期COVID19患者对SARS-CoV-2的唾液IgA应答与全身IgG滴度之间存在分离。然后，使用一种称为尖峰诱饵质谱的创新技术，我们在唾液中发现了新的刺突结合蛋白,最值得注意的是波形蛋白，这与体外病毒感染性增加有关，可以作为对抗COVID-19的治疗靶点。目的：这项工作的目的是鉴定唾液免疫因子和蛋白质，以防止SARS-CoV-2感染，支持开发新的预防COVID-19的策略。
