Yi Dongrong, Zhang Yongxin, Wang Jing, Liu Qian, Ma Ling, Li Quanjie, Guo Saisai, Zheng Ruifang, Li Xiaoyu, Li Xingong, Dong Yijie, Lu Shuaiyao, Zhang Weiguo, Peng Xiaozhong, Cen Shan
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China.
Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
Acta Pharm Sin B. 2025 Feb;15(2):934-946. doi: 10.1016/j.apsb.2024.12.003. Epub 2024 Dec 7.
The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变异株迅速出现，可逃避疫苗接种所诱导的免疫，这给2019冠状病毒病（COVID-19）大流行的控制带来了全球性挑战。因此，开发能广泛预防SARS-CoV-2及相关沙贝病毒的应对措施至关重要。在此，我们开发了一种脂质纳米颗粒（LNP）包裹的信使核糖核酸（mRNA）（mRNA-LNP），其编码SARS-CoV-2全长刺突（S）糖蛋白（称为RG001），该疫苗在非人灵长类动物模型中可提供完全保护。对恒河猴进行两剂RG001肌肉注射免疫可引发针对SARS-CoV-2变异株的强效中和抗体和细胞反应，从而显著保护感染SARS-CoV-2的动物免受急性肺部损伤，并完全抑制所有接受低剂量或高剂量RG001免疫的动物体内的病毒复制。更重要的是，第三剂RG001疫苗接种可引发针对当前流行的XBB和JN.1毒株的有效中和抗体，并且在免疫小鼠中观察到针对SARS-CoV-2奥密克戎变异株（BA.1、XBB.1.16和JN.1）的类似细胞反应。所有这些结果共同有力地支持了RG001在预防关注的SARS-CoV-2变异株（VOCs）感染方面的巨大潜力。
