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一种基于尖峰的 mRNA 疫苗,可诱导仔猪对猪德尔塔冠状病毒产生持久和广泛的保护。

A spike-based mRNA vaccine that induces durable and broad protection against porcine deltacoronavirus in piglets.

机构信息

Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology Ministry of Agriculture, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Nanjing, China.

Institute of Life Sciences, School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China.

出版信息

J Virol. 2024 Sep 17;98(9):e0053524. doi: 10.1128/jvi.00535-24. Epub 2024 Aug 19.

Abstract

UNLABELLED

Coronaviruses (CoVs) are important pathogens for humans and other vertebrates, causing severe respiratory and intestinal infections that have become a threat to public health because of the potential for interspecies transmission between animals and humans. Therefore, the development of safe, effective vaccines remains a top priority for the control of CoV infection. The unique immunological characteristics of vaccines featuring messenger RNA (mRNA) present an advantageous tool for coronavirus vaccine development. Here, we designed two lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) vaccines: one encoding full-length spike (S) protein and the other encoding the spike ectodomain (Se) from porcine deltacoronavirus (PDCoV). Fourteen days after primary immunization, both mRNA vaccines induced high levels of immunoglobulin G and neutralizing antibodies in mice, with the S vaccine showing better performance than the Se vaccine. Passive immune protection of the S mRNA vaccine in suckling piglets was confirmed by the induction of robust PDCoV-specific humoral and cellular immune responses. The S mRNA vaccine also showed better protective effects than the inactivated vaccine. Our results suggest that the novel PDCoV-S mRNA-LNP vaccine may have the potential to combat PDCoV infection.

IMPORTANCE

As an emerging porcine enteropathogenic coronavirus, porcine deltacoronavirus (PDCoV) has the potential for cross-species transmission, attracting extensive attention. Messenger RNA (mRNA) vaccines are a promising option for combating emerging and re-emerging infectious diseases, as evidenced by the demonstrated efficacy of the COVID-19 mRNA vaccine. Here, we first demonstrated that PDCoV-S mRNA-lipid nanoparticle (LNP) vaccines could induce potent humoral and cellular immune responses in mice. An evaluation of passive immune protection of S mRNA vaccines in suckling piglets confirmed that the protective effect of mRNA vaccine was better than that of inactivated vaccine. This study suggests that the PDCoV-S mRNA-LNP vaccine may serve as a potential and novel vaccine candidate for combating PDCoV infection.

摘要

未加标签

冠状病毒(CoV)是人类和其他脊椎动物的重要病原体,可引起严重的呼吸道和肠道感染,由于动物和人类之间种间传播的可能性,这些感染已成为公共卫生的威胁。因此,开发安全有效的疫苗仍然是控制 CoV 感染的首要任务。具有信使 RNA(mRNA)的疫苗的独特免疫特性为冠状病毒疫苗的开发提供了有利的工具。在这里,我们设计了两种包裹在脂质纳米颗粒(LNP)中的 mRNA(mRNA-LNP)疫苗:一种编码全长刺突(S)蛋白,另一种编码猪德尔塔冠状病毒(PDCoV)的刺突外域(Se)。初次免疫后 14 天,两种 mRNA 疫苗均在小鼠中诱导了高水平的免疫球蛋白 G 和中和抗体,S 疫苗的性能优于 Se 疫苗。S mRNA 疫苗在仔猪中的被动免疫保护作用通过诱导强大的 PDCoV 特异性体液和细胞免疫反应得到证实。S mRNA 疫苗的保护效果也优于灭活疫苗。我们的结果表明,新型 PDCoV-S mRNA-LNP 疫苗可能具有预防 PDCoV 感染的潜力。

重要性

作为一种新兴的猪肠道致病性冠状病毒,猪德尔塔冠状病毒(PDCoV)具有种间传播的潜力,引起了广泛关注。mRNA 疫苗在对抗新发和再发传染病方面具有很大的应用前景,这已被证明 COVID-19 mRNA 疫苗的疗效。在这里,我们首次证明 PDCoV-S mRNA-脂质纳米颗粒(LNP)疫苗可在小鼠中诱导强烈的体液和细胞免疫反应。对 S mRNA 疫苗在仔猪中被动免疫保护的评估证实,mRNA 疫苗的保护效果优于灭活疫苗。本研究表明,PDCoV-S mRNA-LNP 疫苗可能成为预防 PDCoV 感染的一种有潜力的新型疫苗候选物。

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