Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA, USA; Department of Biochemistry, University of Washington, Seattle, WA, USA.
Department of Biochemistry, University of Washington, Seattle, WA, USA.
Cell Rep. 2024 Aug 27;43(8):114530. doi: 10.1016/j.celrep.2024.114530. Epub 2024 Jul 25.
Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in 2012 and causes human infections in endemic regions. Vaccines and therapeutics in development against MERS-CoV focus on the spike (S) glycoprotein to prevent viral entry into target cells. These efforts are limited by a poor understanding of antibody responses elicited by infection. Here, we analyze S-directed antibody responses in plasma collected from MERS-CoV-infected individuals. We observe that binding and neutralizing antibodies peak 1-6 weeks after symptom onset/hospitalization, persist for at least 6 months, and neutralize human and camel MERS-CoV strains. We show that the MERS-CoV S subunit is immunodominant and that antibodies targeting S, particularly the receptor-binding domain (RBD), account for most plasma neutralizing activity. Antigenic site mapping reveals that plasma antibodies frequently target RBD epitopes, whereas targeting of S subunit epitopes is rare. Our data reveal the humoral immune responses elicited by MERS-CoV infection, which will guide vaccine and therapeutic design.
中东呼吸综合征冠状病毒（MERS-CoV）于 2012 年首次出现，导致流行地区的人类感染。针对 MERS-CoV 的正在开发的疫苗和疗法集中在刺突（S）糖蛋白上，以防止病毒进入靶细胞。这些努力受到对感染引起的抗体反应的理解不足的限制。在这里，我们分析了从 MERS-CoV 感染个体中采集的血浆中的 S 定向抗体反应。我们观察到，结合和中和抗体在症状出现/住院后 1-6 周达到峰值，至少持续 6 个月，并中和人类和骆驼 MERS-CoV 株。我们表明，MERS-CoV S 亚基是免疫显性的，并且针对 S 的抗体，特别是受体结合域（RBD），占大多数血浆中和活性。抗原表位作图显示，血浆抗体经常针对 RBD 表位，而针对 S 亚基表位的情况很少。我们的数据揭示了 MERS-CoV 感染引起的体液免疫反应，这将指导疫苗和治疗药物的设计。
