Comparison of protection against mpox following mRNA or modified vaccinia Ankara vaccination in nonhuman primates

IF 45.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell Pub Date : 2024-09-04 DOI:10.1016/j.cell.2024.08.043

Eric M. Mucker, Alec W. Freyn, Sandra L. Bixler, Deniz Cizmeci, Caroline Atyeo, Patricia L. Earl, Harini Natarajan, Genesis Santos, Tiffany R. Frey, Rafael H. Levin, Anusha Meni, Guha A. Arunkumar, Daniel Stadlbauer, Patricia A. Jorquera, Hamilton Bennett, Joshua C. Johnson, Kath Hardcastle, Jeffrey L. Americo, Catherine A. Cotter, Jeff W. Koehler, Jay W. Hooper

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Abstract

In 2022, mpox virus (MPXV) spread worldwide, causing 99,581 mpox cases in 121 countries. Modified vaccinia Ankara (MVA) vaccine use reduced disease in at-risk populations but failed to deliver complete protection. Lag in manufacturing and distribution of MVA resulted in additional MPXV spread, with 12,000 reported cases in 2023 and an additional outbreak in Central Africa of clade I virus. These outbreaks highlight the threat of zoonotic spillover by Orthopoxviruses. mRNA-1769, an mRNA-lipid nanoparticle (LNP) vaccine expressing MPXV surface proteins, was tested in a lethal MPXV primate model. Similar to MVA, mRNA-1769 conferred protection against challenge and further mitigated symptoms and disease duration. Antibody profiling revealed a collaborative role between neutralizing and Fc-functional extracellular virion (EV)-specific antibodies in viral restriction and ospinophagocytic and cytotoxic antibody functions in protection against lesions. mRNA-1769 enhanced viral control and disease attenuation compared with MVA, highlighting the potential for mRNA vaccines to mitigate future pandemic threats.

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比较非人灵长类动物接种 mRNA 或改良安卡拉疫苗后对麻风腮病毒的保护作用

2022 年，麻疹病毒（MPXV）在全球蔓延，导致 121 个国家出现 99,581 例麻疹病例。改良安卡拉疫苗（MVA）的使用减少了高危人群的发病率，但未能提供全面保护。改良安卡拉疫苗（MVA）生产和分销的滞后导致了更多的 MPXV 传播，2023 年报告了 12,000 例病例，在中非又爆发了一次 I 支病毒疫情。mRNA-1769是一种表达MPXV表面蛋白的mRNA-脂质纳米颗粒（LNP）疫苗，已在一种致命的MPXV灵长类动物模型中进行了测试。与 MVA 相似，mRNA-1769 也能抵御挑战，并进一步减轻症状和缩短病程。抗体分析表明，中和抗体和Fc功能细胞外病毒（EV）特异性抗体在病毒限制中起着协同作用，而嗜酸性粒细胞抗体和细胞毒性抗体的功能则在防止病变中起着保护作用。与MVA相比，mRNA-1769增强了病毒控制和疾病缓解的能力，突显了mRNA疫苗缓解未来大流行威胁的潜力。

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来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.