Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2024-12-24 Epub Date: 2024-12-06 DOI:10.1016/j.celrep.2024.115036

Cara W Chao, Kaitlin R Sprouse, Marcos C Miranda, Nicholas J Catanzaro, Miranda L Hubbard, Amin Addetia, Cameron Stewart, Jack T Brown, Annie Dosey, Adian Valdez, Rashmi Ravichandran, Grace G Hendricks, Maggie Ahlrichs, Craig Dobbins, Alexis Hand, Jackson McGowan, Boston Simmons, Catherine Treichel, Isabelle Willoughby, Alexandra C Walls, Andrew T McGuire, Elizabeth M Leaf, Ralph S Baric, Alexandra Schäfer, David Veesler, Neil P King

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引用次数: 0

Abstract

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.

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蛋白质纳米颗粒疫苗诱导针对MERS-CoV的有效中和抗体反应。

中东呼吸综合征冠状病毒（MERS-CoV）是一种导致人类严重呼吸道疾病的冠状病毒。目前还没有针对中东呼吸综合征冠状病毒的许可疫苗，只有少数候选疫苗处于I期临床试验中。在这里，我们利用计算设计的蛋白质纳米颗粒平台开发MERS-CoV疫苗，该平台已经产生了针对各种包膜病毒的安全免疫原性疫苗，包括一种获得许可的严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）疫苗。显示刺突(S)来源抗原的双组分纳米颗粒诱导中和反应并保护小鼠免受小鼠适应性MERS-CoV的攻击。表位定位揭示了免疫原引起的主要反应，显示了预灌注稳定的S-2P三聚体、受体结合域（RBD）或n端结构域（NTD）。RBD纳米颗粒引发针对RBD中多个非重叠表位的抗体。我们的研究结果证明了MERS-CoV双组分纳米颗粒候选疫苗的潜力，并表明该平台技术可以广泛应用于乙型冠状病毒疫苗的开发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.