The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) caused an ongoing unprecedented global public health crises of coronavirus disease in 2019 (CoVID-19). The precipitously increased death rates, its impact on livelihood and trembling economies warrant the urgent development of SARS-CoV-2 vaccine which would be safe, efficacious and scalable. Owing to unavailability of the vaccine, we propose a de novo synthesised avian orthoavulavirus 1 (AOaV-1)-based topical respiratory vaccine candidate against CoVID-19. Avirulent strain of Newcastle disease virus, proto-type virus of AOaV-1, was engineered to express full length spike (S) glycoprotein which is highly neutralizing and major protective antigen of the SARS-CoV-2. Broad-scale in vitro characterization of recombinant vaccine candidate demonstrated efficient co-expression of the hemagglutinin-neuraminidase (HN) of AOaV-1 and S protein of SARS-CoV-2, and comparable replication kinetics were observed in cell culture model. The recombinant vaccine candidate virus actively replicated and spread within cells independently of exogenous trypsin. Interestingly, incorporation of S protein of SARS-CoV-2 into the recombinant AOaV-1 particles attributed the sensitivity to anti-SARS-CoV-2 antiserum and more prominently to anti-AOaV-1 antiserum. Finally, our results demonstrated that the recombinant vaccine vector stably expressed S protein after multiple propagation in chicken embryonated eggs, and this expression did not significantly impact the in vitro growth characteristics of the recombinant. Taken together, the presented respiratory vaccine candidate is highly attenuated in primates per se, safe and lacking pre-existing immunity in human, and carries the potential for accelerated vaccine development against CoVID-19 for clinical studies.

中文翻译：

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抗SARS-CoV-2的可扩展主题向量疫苗候选者。

严重的急性呼吸系统综合症冠状病毒2（SARS-CoV-2）在2019年引起了持续不断的全球性冠状病毒疾病全球公共卫生危机（CoVID-19）。死亡率的急剧上升，其对生计的影响和经济的动荡，都保证了迫切需要开发出SARS-CoV-2疫苗的安全性，有效性和可扩展性。由于没有疫苗，我们提出了一种基于新合成的抗CoVID-19的禽正痘病毒1（AOaV-1）的局部呼吸道疫苗候选物。新城疫病毒的无毒株，即AOaV-1的原型病毒，经过工程改造后可以表达全长穗状糖（S）糖蛋白，该糖蛋白高度中和且是SARS-CoV-2的主要保护性抗原。重组疫苗候选物的大规模体外表征证明了AOaV-1的血凝素神经氨酸酶（HN）和SARS-CoV-2的S蛋白的有效共表达，并且在细胞培养模型中观察到了相当的复制动力学。重组疫苗候选病毒独立于外源胰蛋白酶活跃地复制并在细胞内传播。有趣的是，将SARS-CoV-2的S蛋白掺入重组AOaV-1颗粒中可归因于对SARS-CoV-2抗血清的敏感性，以及对抗AOaV-1抗血清的敏感性。最后，我们的结果证明重组疫苗载体在鸡胚卵中多次繁殖后稳定表达S蛋白，这种表达不会显着影响重组体的体外生长特性。在一起