Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
St. Jude Children's Research Hospital Graduate School of Biomedical Sciences, Memphis, Tennessee, USA.
Microbiol Spectr. 2023 Feb 14;11(1):e0424022. doi: 10.1128/spectrum.04240-22. Epub 2023 Jan 25.
The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in December of 2019 and is responsible for millions of infections and deaths across the globe. Vaccination against SARS-CoV-2 has proven effective to contain the spread of the virus and reduce disease. The production and distribution of these vaccines occurred at a remarkable pace, largely through the employment of the novel mRNA platform. However, interruptions in supply chain and high demand for clinical grade reagents have impeded the manufacture and distribution of mRNA vaccines at a time when accelerated vaccine deployment is crucial. Furthermore, the emergence of SARS-CoV-2 variants across the globe continues to threaten the efficacy of vaccines encoding the ancestral virus spike protein. Here, we report results from preclinical studies on mRNA vaccines developed using a proprietary mRNA production process developed by GreenLight Biosciences. Two mRNA vaccines encoding the full-length, nonstabilized SARS-CoV-2 spike protein, GLB-COV2-042 and GLB-COV2-043, containing uridine and pseudouridine, respectively, were evaluated in rodents for their immunogenicity and protection from SARS-CoV-2 challenge with the ancestral strain and the Alpha (B.1.1.7) and Beta (B.1.351) variants. In mice and hamsters, both vaccines induced robust spike-specific binding and neutralizing antibodies, and in mice, vaccines induced significant T cell responses with a clear Th1 bias. In hamsters, both vaccines conferred significant protection following challenge with SARS-CoV-2 as assessed by weight loss, viral load, and virus replication in the lungs and nasopharynx. These results support the development of GLB-COV2-042 and GLB-COV2-043 for clinical use. SARS-CoV-2 continues to disrupt everyday life and cause excess morbidity and mortality worldwide. Vaccination has been key to quelling the impact of this respiratory pathogen, and mRNA vaccines have led the charge on this front. However, the emergence of SARS-CoV-2 variants has sparked fears regarding vaccine efficacy. Furthermore, SARS-CoV-2 vaccines continue to be unevenly distributed across the globe. For these reasons and despite the success of emergency authorized and licensed SARS-CoV-2 vaccines, additional vaccines are needed to meet public health demands. The studies presented here are significant as they demonstrate robust protective efficacy of mRNA vaccines developed by GreenLight Biosciences against not only wild-type SARS-CoV-2, but also Alpha and Beta variants. These results support the progression of GreenLight Biosciences SARS-CoV-2 mRNA vaccines to clinical trials as another defense against SARS-CoV-2.
新型冠状病毒(SARS-CoV-2)于 2019 年 12 月被发现,它在全球范围内导致了数百万人感染和死亡。接种 SARS-CoV-2 疫苗已被证明可有效控制病毒传播并降低疾病严重程度。这些疫苗的生产和分发速度非常快,主要是通过采用新型 mRNA 平台。然而,供应链中断和对临床级试剂的高需求阻碍了 mRNA 疫苗的生产和分发,而此时加速疫苗部署至关重要。此外,全球 SARS-CoV-2 变体的出现继续威胁到编码原始病毒刺突蛋白的疫苗的功效。在这里,我们报告了使用 GreenLight Biosciences 开发的专有 mRNA 生产工艺开发的 mRNA 疫苗的临床前研究结果。两种编码全长、非稳定 SARS-CoV-2 刺突蛋白的 mRNA 疫苗,GLB-COV2-042 和 GLB-COV2-043,分别含有尿嘧啶和假尿嘧啶,在啮齿动物中评估了其免疫原性和对原始毒株和 Alpha(B.1.1.7)和 Beta(B.1.351)变体的 SARS-CoV-2 攻击的保护作用。在小鼠和仓鼠中,两种疫苗均诱导了强烈的刺突特异性结合和中和抗体,并且在小鼠中,疫苗诱导了明显的 T 细胞应答,具有明显的 Th1 偏向。在仓鼠中,两种疫苗在 SARS-CoV-2 攻击后均提供了显著的保护作用,表现为体重减轻、病毒载量以及肺部和鼻咽部的病毒复制减少。这些结果支持 GLB-COV2-042 和 GLB-COV2-043 的临床开发。SARS-CoV-2 继续扰乱日常生活并在全球范围内造成过多的发病率和死亡率。接种疫苗是控制这种呼吸道病原体影响的关键,而 mRNA 疫苗在这方面处于领先地位。然而,SARS-CoV-2 变体的出现引发了对疫苗功效的担忧。此外,SARS-CoV-2 疫苗在全球的分布仍然不均匀。出于这些原因,尽管紧急授权和许可的 SARS-CoV-2 疫苗取得了成功,但仍需要额外的疫苗来满足公共卫生需求。这里介绍的研究具有重要意义,因为它们证明了 GreenLight Biosciences 开发的 mRNA 疫苗对野生型 SARS-CoV-2 以及 Alpha 和 Beta 变体具有强大的保护效力。这些结果支持 GreenLight Biosciences SARS-CoV-2 mRNA 疫苗进入临床试验,作为对抗 SARS-CoV-2 的另一种防御手段。
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