作者：转化医学平台
2020年4月7日，来自美国爱荷华大学、佐治亚大学的研究人员在《mBio》期刊上发表了一篇题为“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。疫苗利用一种无害病毒将一种MERS-CoV蛋白递送到细胞内以产生免疫反应，这为开发新冠状病毒病的疫苗提供新策略。
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新兴的CoV疫苗，例如SARS-CoV-2，该疫苗可导致COVID-19。
研究人员测试了一种经过基因改造后对MERS-CoV敏感的候选疫苗，这该疫苗是由一种称为副流感病毒5（PIV5）的RNA病毒改造而来，它会引起犬类的犬窝咳，但是对人类无害。研究人员在病毒中添加了一个基因，使被感染的细胞产生参与MERS感染的S刺突糖蛋白。研究结果表明，鼻内给予单剂疫苗可有效地引起感染细胞产生S蛋白，进而触发动物宿主体内对该蛋白的免疫反应。
小鼠在接受疫苗四周后，将它们暴露于MERS病毒株中。还向两组接受不疫苗处理的小鼠给予MERS病毒（PIV5疫苗（不含S蛋白基因的疫苗）和含灭活MERS病毒的疫苗）。
重组PIV5的产生和表征
使用基因改造后PIV5病毒来免疫的所有小鼠在MERS病毒感染中存活。相反，用无S的PIV5免疫的所有小鼠均死于感染。灭活MERS病毒的疫苗只能保护25％的小鼠免于致命感染。
PIV5-MERS-S单剂量鼻内免疫可完全保护hDPP4 KI小鼠不受致死的MERS-CoV侵害
总体而言，我们的研究表明PIV5-MERS-S是针对MERS-CoV感染的有希望的有效疫苗候选者。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新兴的CoV疫苗，例如SARS-CoV-2，该疫苗可导致COVID-19。
将病毒用作基因传递载体是一非常具有潜力的策略，而找到一种有效的疫苗来对抗COVID-19病毒是一项与时间赛跑的竞赛。
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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