Table_1_A novel approach to designing viral precision vaccines applied to SARS-CoV-2.docx

Efficient precision vaccines against several highly pathogenic zoonotic viruses are currently lacking. Proteolytic activation is instrumental for a number of these viruses to gain host-cell entry and develop infectivity. For SARS-CoV-2, this process is enhanced by the insertion of a furin cleavage site at the junction of the spike protein S1/S2 subunits upstream of the metalloprotease TMPRSS2 common proteolytic site. Here, we describe a new approach based on specific epitopes selection from the region involved in proteolytic activation and infectivity for the engineering of precision candidate vaccinating antigens. This approach was developed through its application to the design of SARS-CoV-2 cross-variant candidates vaccinating antigens. It includes an in silico structural analysis of the viral region involved in infectivity, the identification of conserved immunogenic epitopes and the selection of those eliciting specific immune responses in infected people. The following step consists of engineering vaccinating antigens that carry the selected epitopes and mimic their 3D native structure. Using this approach, we demonstrated through a Covid-19 patient-centered study of a 500 patients’ cohort, that the epitopes selected from SARS-CoV-2 protein S1/S2 junction elicited a neutralizing antibody response significantly associated with mild and asymptomatic COVID-19 (p

目前，针对多种高致病性人畜共患病病毒的高效精准疫苗尚属缺失。蛋白酶激活对于众多病毒获取宿主细胞进入并发展感染性至关重要。对于SARS-CoV-2病毒，此过程因在刺突蛋白S1/S2亚单位连接处上游插入furin裂解位点而得到增强，该位点位于金属蛋白酶TMPRSS2的常见蛋白酶解位点之前。本研究描述了一种基于从参与蛋白酶激活和感染性区域选择特定表位的创新方法，以用于精确候选疫苗抗原的工程化。该方法通过将其应用于SARS-CoV-2跨变体候选疫苗抗原的设计而得以发展。它包括对涉及感染性的病毒区域进行计算机结构分析，识别保守的免疫原性表位，以及选择那些在感染者中引起特定免疫反应的表位。随后的一步是工程化携带所选表位并模拟其三维原生态结构的疫苗抗原。通过一项以500名COVID-19患者为中心的研究，我们展示了从SARS-CoV-2蛋白S1/S2连接处选出的表位引发的中和抗体反应与轻微和无症状COVID-19显著相关（p