The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA.
The Translational Genomics Research Institute (TGen), Flagstaff, AZ, USA.
Cell Rep. 2022 Jul 5;40(1):111022. doi: 10.1016/j.celrep.2022.111022. Epub 2022 Jun 13.
The COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Many vaccinated subjects are previously naive to SARS-CoV-2; however, almost all have previously encountered other coronaviruses (CoVs), and the role of this immunity in shaping the vaccine response remains uncharacterized. Here, we use longitudinal samples and highly multiplexed serology to identify mRNA-1273 vaccine-induced antibody responses against a range of CoV Spike epitopes, in both phylogenetically conserved and non-conserved regions. Whereas reactivity to SARS-CoV-2 epitopes shows a delayed but progressive increase following vaccination, we observe distinct kinetics for the endemic CoV homologs at conserved sites in Spike S2: these become detectable sooner and decay at later time points. Using homolog-specific antibody depletion and alanine-substitution experiments, we show that these distinct trajectories reflect an evolving cross-reactive response that can distinguish rare, polymorphic residues within these epitopes. Our results reveal mechanisms for the formation of antibodies with broad reactivity against CoVs.
COVID-19 大流行引发了首次针对冠状病毒的广泛疫苗接种运动。许多接种疫苗的受试者以前对 SARS-CoV-2 没有免疫力；然而，几乎所有人以前都曾接触过其他冠状病毒（CoVs），这种免疫在塑造疫苗反应中的作用仍未被描述。在这里，我们使用纵向样本和高度多重化的血清学方法，在 SARS-CoV-2 刺突蛋白的进化保守和非保守区域中，鉴定了 mRNA-1273 疫苗诱导的针对一系列 CoV 刺突表位的抗体反应。虽然对 SARS-CoV-2 表位的反应在接种疫苗后会出现延迟但逐渐增加，但我们观察到 Spike S2 中保守位点的地方性 CoV 同源物的动力学不同：这些同源物更早被检测到，并且在稍后的时间点衰减。使用同源特异性抗体耗竭和丙氨酸取代实验，我们表明这些不同的轨迹反映了一种不断变化的交叉反应性反应，这种反应可以区分这些表位内罕见的多态性残基。我们的研究结果揭示了针对 CoV 形成具有广泛反应性的抗体的机制。
