中东呼吸综合征冠状病毒刺突蛋白疫苗诱导产生的N端结构域特异性抗体比受体结合结构域特异性抗体更具保护性。
MERS-CoV spike vaccine-induced N-terminal domain-specific antibodies are more protective than receptor binding domain-specific antibodies.
作者信息
Abiona Olubukola M, Wang Nianshuang, Leist Sarah R, Schäfer Alexandra, Cockrell Adam S, Wang Lingshu, Bangaru Sandhya, Stevens Laura, Graham Rachel L, Kocher Jacob F, Tsybovsky Yaroslav, Kanekiyo Masaru, Kumar Azad, Morabito Kaitlyn M, Rosen Osnat, Shi Wei, Werner Anne, Zhang Yi, Ziwawo Cynthia, Dzuvor Christian K O, Palandjian Charis, Eastman Connor, Matthews Hannah R, Joseph Jeswin, Chappell James D, Kong Wing-Pui, Mascola John R, Ward Andrew B, Denison Mark R, Baric Ralph, McLellan Jason S, Graham Barney S, Corbett-Helaire Kizzmekia S
机构信息
Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
出版信息
iScience. 2024 Dec 18;28(2):111632. doi: 10.1016/j.isci.2024.111632. eCollection 2025 Feb 21.
The COVID-19 pandemic underscores the need to prepare for future emerging coronavriuses (CoVs) by understanding the principles behind effective CoV vaccine design such as protective immunity and antibody responses. To study which epitopes and subdomains contribute to protection, we utilized the prefusion-stabilized spike protein of MERS-CoV, MERS S-2P, as a vaccine immunogen. Vaccination with MERS S-2P elicited both receptor-binding domain (RBD)- and non-RBD-specific antibodies, including N-terminal domain (NTD)-specific G2-and CDC2-A2-like antibodies. Intriguingly, the immunogen MERS S-2P_ΔRBD, MERS S-2P with the RBDs removed, protects comparably to S1 and S-2P immunogens against MERS-CoV challenge. Moreover, passive transfer studies of polyclonal IgG from MERS S-2P immunized mice depleted of subdomain-specific antibodies demonstrated that non-RBD antibodies protected more than non-NTD antibodies. Altogether, these findings illustrate that protection is not solely driven by RBD-specific antibodies and highlights the importance of targeting non-RBD sites in future CoV vaccine designs.
新冠疫情凸显了通过了解有效冠状病毒（CoV）疫苗设计背后的原理（如保护性免疫和抗体反应）来为未来出现的冠状病毒做准备的必要性。为了研究哪些表位和亚结构域有助于提供保护，我们利用中东呼吸综合征冠状病毒（MERS-CoV）的预融合稳定刺突蛋白MERS S-2P作为疫苗免疫原。用MERS S-2P进行疫苗接种可引发受体结合域（RBD）特异性抗体和非RBD特异性抗体，包括N端结构域（NTD）特异性的G2和CDC2-A2样抗体。有趣的是，免疫原MERS S-2P_ΔRBD（去除了RBD的MERS S-2P）在抵抗MERS-CoV攻击方面与S1和S-2P免疫原具有相当的保护作用。此外，对来自MERS S-2P免疫小鼠的多克隆IgG进行的被动转移研究，这些小鼠的亚结构域特异性抗体已被耗尽，结果表明非RBD抗体的保护作用强于非NTD抗体。总之，这些发现表明保护作用并非仅由RBD特异性抗体驱动，并突出了在未来CoV疫苗设计中靶向非RBD位点的重要性。
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