The COVID-19 pandemic caused by the emergent SARS-CoV-2 coronavirus threatens global public health and there is an urgent need to develop safe and effective vaccines. Here we report the generation and the preclinical evaluation of a novel replication-defective gorilla adenovirus-vectored vaccine encoding the pre-fusion stabilized Spike (S) protein of SARS-CoV2. We show that our vaccine candidate, GRAd-COV2, is highly immunogenic both in mice and macaques, eliciting both functional antibodies which neutralize SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and a robust, Th1-dominated cellular response in the periphery and in the lung. We show here that the pre-fusion stabilized Spike antigen is superior to the wild type in inducing ACE2-interfering, SARS-CoV2 neutralizing antibodies. To face the unprecedented need for vaccine manufacturing at massive scale, different GRAd genome deletions were compared to select the vector backbone showing the highest productivity in stirred tank bioreactors. This preliminary dataset identified GRAd-COV2 as a potential COVID-19 vaccine candidate, supporting the translation of GRAd-COV2 vaccine in a currently ongoing Phase I clinical trial (NCT04528641).

中文翻译：

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新型大猩猩腺病毒候选疫苗对COVID-19的免疫原性

由新出现的SARS-CoV-2冠状病毒引起的COVID-19大流行威胁全球公共卫生，因此迫切需要开发安全有效的疫苗。在这里，我们报告新型复制缺陷大猩猩腺病毒载体疫苗的产生和临床前评估，该疫苗编码SARS-CoV2融合前稳定的Spike（S）蛋白。我们显示，我们的候选疫苗GRAd-COV2在小鼠和猕猴中均具有高度免疫原性，引起中和SARS-CoV-2感染并阻断Spike蛋白与ACE2受体结合的功能性抗体，以及以Th1为主导的强大细胞在周围和肺部反应。我们在这里显示，融合前稳定的Spike抗原在诱导ACE2干扰，SARS-CoV2中和抗体方面优于野生型。为了应对大规模生产疫苗的空前需求，将不同的GRAd基因组缺失进行了比较，以选择在搅拌罐式生物反应器中显示最高生产率的载体骨架。该初步数据集将GRAd-COV2鉴定为潜在的COVID-19候选疫苗，在当前正在进行的I期临床试验（NCT04528641）中支持GRAd-COV2疫苗的翻译。