Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection
Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection
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DOI：
10.1128/mbio.00554-20
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发表时间：
2020-03-01
期刊：
影响因子：
6.4
通讯作者：
He, Biao
中科院分区：
文献类型：
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作者：
Li, Kun;Li, Zhuo;He, Biao
中东呼吸综合征冠状病毒 (MERS-CoV) 可引起人类严重和致命的急性呼吸道疾病，自 2012 年首次发现以来，该病毒一直在中东地区流行。目前尚未有针对 MERS-CoV 的批准疫苗或疗法。在这项研究中，我们在人 DPP4 敲入 C57BL/6 同类小鼠模型 (hDPP4 KI) 中评估了表达 MERS-CoV 包膜刺突蛋白 (PIV5/MERS-S) 的副流感病毒 5 (PIV5) 疫苗。单剂量鼻内免疫后，PIV5-MERS-S 在 hDPP4 KI 小鼠中诱导中和抗体和强烈的 T 细胞反应。单次鼻内给药 10(4) PIV5-MERS-S 提供了针对小鼠适应的 MERS-CoV (MERSMA 6.1.2) 致命攻击的完全保护，并改善了肺部的病毒清除率。相比之下，使用 10(6) PFU 紫外线灭活 MERSMA 6.1.2 与 Imject 明矾混合的单剂量肌肉内免疫仅对 25% 的免疫小鼠提供了保护。有趣的是，仅在用灭活的中东呼吸综合征冠状病毒免疫的小鼠的肺部观察到嗜酸性粒细胞的涌入，这表明存在超敏反应。总体而言，我们的研究表明 PIV5-MERS-S 是一种有前景的有效对抗 MERS-CoV 感染的候选疫苗。 重要性 MERS-CoV 会导致人类致命感染，但目前还没有疫苗。我们的工作表明 PIV5 是开发 MERS 疫苗的有前途的载体。此外，基于 PIV5 的 MERS 疫苗的成功可用于开发针对新兴 CoV 的疫苗，例如引起 COVID-19 的 SARS-CoV-2。
Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 10(4) PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERSMA 6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 10(6) PFU UV-inactivated MERSMA 6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection.IMPORTANCE MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19.