Chao Cara W, Sprouse Kaitlin R, Miranda Marcos C, Catanzaro Nicholas J, Hubbard Miranda L, Addetia Amin, Stewart Cameron, Brown Jack T, Dosey Annie, Valdez Adian, Ravichandran Rashmi, Hendricks Grace G, Ahlrichs Maggie, Dobbins Craig, Hand Alexis, McGowan Jackson, Simmons Boston, Treichel Catherine, Willoughby Isabelle, Walls Alexandra C, McGuire Andrew T, Leaf Elizabeth M, Baric Ralph S, Schäfer Alexandra, Veesler David, King Neil P
Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Graduate Program in Molecular and Cellular Biology, University of Washington, Seattle, WA 98195, USA.
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Cell Rep. 2024 Dec 24;43(12):115036. doi: 10.1016/j.celrep.2024.115036. Epub 2024 Dec 6.
Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus that causes severe respiratory illness in humans. There are no licensed vaccines against MERS-CoV and only a few candidates in phase I clinical trials. Here, we develop MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including a licensed vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two-component nanoparticles displaying spike (S)-derived antigens induce neutralizing responses and protect mice against challenge with mouse-adapted MERS-CoV. Epitope mapping reveals the dominant responses elicited by immunogens displaying the prefusion-stabilized S-2P trimer, receptor binding domain (RBD), or N-terminal domain (NTD). An RBD nanoparticle elicits antibodies targeting multiple non-overlapping epitopes in the RBD. Our findings demonstrate the potential of two-component nanoparticle vaccine candidates for MERS-CoV and suggest that this platform technology could be broadly applicable to betacoronavirus vaccine development.
中东呼吸综合征冠状病毒（MERS-CoV）是一种β冠状病毒，可导致人类严重呼吸道疾病。目前尚无针对MERS-CoV的获批疫苗，仅有少数候选疫苗处于I期临床试验阶段。在此，我们利用一种通过计算机设计的蛋白质纳米颗粒平台开发MERS-CoV疫苗，该平台已研发出针对多种包膜病毒的安全且具有免疫原性的疫苗，包括一种针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的获批疫苗。展示刺突（S）衍生抗原的双组分纳米颗粒可诱导中和反应，并保护小鼠免受适应小鼠的MERS-CoV攻击。表位作图揭示了展示预融合稳定化S-2P三聚体、受体结合域（RBD）或N端结构域（NTD）的免疫原引发的主要反应。一种RBD纳米颗粒可引发靶向RBD中多个非重叠表位的抗体。我们的研究结果证明了双组分纳米颗粒候选疫苗用于MERS-CoV的潜力，并表明该平台技术可广泛应用于β冠状病毒疫苗的开发。
