作者：轉化醫學平臺
2020年4月7日，來自美國愛荷華大學、佐治亞大學的研究人員在《mBio》期刊上發表了一篇題為“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”的文章。疫苗利用一種無害病毒將一種MERS-CoV蛋白遞送到細胞內以產生免疫反應，這為開發新冠狀病毒病的疫苗提供新策略。
我們的工作表明，PIV5是開發MERS疫苗的有前途的載體。此外，基於PIV5的MERS疫苗的成功可用於開發新興的CoV疫苗，例如SARS-CoV-2，該疫苗可導致COVID-19。
研究人員測試了一種經過基因改造後對MERS-CoV敏感的候選疫苗，這該疫苗是由一種稱為副流感病毒5（PIV5）的RNA病毒改造而來，它會引起犬類的犬窩咳，但是對人類無害。研究人員在病毒中添加了一個基因，使被感染的細胞產生參與MERS感染的S刺突糖蛋白。研究結果表明，鼻內給予單劑疫苗可有效地引起感染細胞產生S蛋白，進而觸發動物宿主體內對該蛋白的免疫反應。
小鼠在接受疫苗四周後，將它們暴露於MERS病毒株中。還向兩組接受不疫苗處理的小鼠給予MERS病毒（PIV5疫苗（不含S蛋白基因的疫苗）和含滅活MERS病毒的疫苗）。
重組PIV5的產生和表徵
使用基因改造後PIV5病毒來免疫的所有小鼠在MERS病毒感染中存活。相反，用無S的PIV5免疫的所有小鼠均死於感染。滅活MERS病毒的疫苗只能保護25％的小鼠免於致命感染。
PIV5-MERS-S單劑量鼻內免疫可完全保護hDPP4 KI小鼠不受致死的MERS-CoV侵害
總體而言，我們的研究表明PIV5-MERS-S是針對MERS-CoV感染的有希望的有效疫苗候選者。我們的工作表明，PIV5是開發MERS疫苗的有前途的載體。此外，基於PIV5的MERS疫苗的成功可用於開發新興的CoV疫苗，例如SARS-CoV-2，該疫苗可導致COVID-19。
將病毒用作基因傳遞載體是一非常具有潛力的策略，而找到一種有效的疫苗來對抗COVID-19病毒是一項與時間賽跑的競賽。
Abstract
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 104 PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERSMA6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 106 PFU UV-inactivated MERSMA6.1.2 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.
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