Institut für Virologie, Freie Universität Berlin, Berlin, Germany.
Institut für Tierpathologie, Freie Universität Berlin, Berlin, Germany; Tiermedizinisches Zentrum für Resistenzforschung, Freie Universität Berlin, Berlin, Germany.
Cell Rep. 2021 Aug 3;36(5):109493. doi: 10.1016/j.celrep.2021.109493. Epub 2021 Jul 20.
Safe and effective vaccines are urgently needed to stop the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We construct a series of live attenuated vaccine candidates by large-scale recoding of the SARS-CoV-2 genome and assess their safety and efficacy in Syrian hamsters. Animals were vaccinated with a single dose of the respective recoded virus and challenged 21 days later. Two of the tested viruses do not cause clinical symptoms but are highly immunogenic and induce strong protective immunity. Attenuated viruses replicate efficiently in the upper but not in the lower airways, causing only mild pulmonary histopathology. After challenge, hamsters develop no signs of disease and rapidly clear challenge virus: at no time could infectious virus be recovered from the lungs of infected animals. The ease with which attenuated virus candidates can be produced and administered favors their further development as vaccines to combat the ongoing pandemic.
我们需要安全有效的疫苗来阻止由严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）引起的大流行。我们通过对 SARS-CoV-2 基因组进行大规模重编码构建了一系列减毒活疫苗候选物，并在叙利亚仓鼠中评估了它们的安全性和有效性。动物接受单剂量的相应重编码病毒接种，并在 21 天后进行攻毒。两种测试的病毒不会引起临床症状，但具有高度免疫原性，并诱导强烈的保护性免疫。减毒病毒在上呼吸道中高效复制，但在下呼吸道中不能复制，仅引起轻微的肺组织病理学改变。攻毒后，仓鼠没有出现疾病迹象，迅速清除攻毒病毒：在任何时间都无法从感染动物的肺部回收感染性病毒。减毒病毒候选物易于生产和使用，有利于将其进一步开发为疫苗，以应对持续的大流行。
