Protection efficacy of mRNA-based SARS-CoV-2 variant vaccine in non-human primates

IF 14.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Acta Pharmaceutica Sinica. B Pub Date : 2025-02-01 DOI:10.1016/j.apsb.2024.12.003
Dongrong Yi , Yongxin Zhang , Jing Wang , Qian Liu , Ling Ma , Quanjie Li , Saisai Guo , Ruifang Zheng , Xiaoyu Li , Xingong Li , Yijie Dong , Shuaiyao Lu , Weiguo Zhang , Xiaozhong Peng , Shan Cen
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Abstract

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).

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严重急性呼吸系统综合症冠状病毒 2(SARS-CoV-2)变种的迅速出现,逃避了疫苗接种所产生的免疫力,这对控制 2019 年冠状病毒病(COVID-19)大流行构成了全球性挑战。因此,开发能够广泛抵御 SARS-CoV-2 和相关沙巴病毒的对策至关重要。在此,我们开发了一种脂质纳米粒子(LNP)包裹的mRNA(mRNA-LNP),该mRNA编码SARS-CoV-2的全长穗状(S)糖蛋白(称为RG001),可在非人灵长类动物模型中提供完全保护。对恒河猴肌肉注射两剂RG001,可引起针对SARS-CoV-2变体的强效中和抗体和细胞反应,从而显著保护SARS-CoV-2感染动物免受急性肺部病变的影响,并完全抑制所有低剂量或高剂量RG001免疫动物的病毒复制。更重要的是,接种第三剂 RG001 疫苗后,免疫小鼠体内产生了针对当前流行的 XBB 和 JN.1 株的有效中和抗体,并观察到针对 SARS-CoV-2 Omicron 变种(BA.1、XBB.1.16 和 JN.1)的类似细胞反应。所有这些结果都有力地证明了 RG001 在预防 SARS-CoV-2 变异株(VOCs)感染方面的巨大潜力。
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来源期刊
Acta Pharmaceutica Sinica. B
Acta Pharmaceutica Sinica. B Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics
CiteScore
22.40
自引率
5.50%
发文量
1051
审稿时长
19 weeks
期刊介绍: The Journal of the Institute of Materia Medica, Chinese Academy of Medical Sciences, and the Chinese Pharmaceutical Association oversees the peer review process for Acta Pharmaceutica Sinica. B (APSB). Published monthly in English, APSB is dedicated to disseminating significant original research articles, rapid communications, and high-quality reviews that highlight recent advances across various pharmaceutical sciences domains. These encompass pharmacology, pharmaceutics, medicinal chemistry, natural products, pharmacognosy, pharmaceutical analysis, and pharmacokinetics. A part of the Acta Pharmaceutica Sinica series, established in 1953 and indexed in prominent databases like Chemical Abstracts, Index Medicus, SciFinder Scholar, Biological Abstracts, International Pharmaceutical Abstracts, Cambridge Scientific Abstracts, and Current Bibliography on Science and Technology, APSB is sponsored by the Institute of Materia Medica, Chinese Academy of Medical Sciences, and the Chinese Pharmaceutical Association. Its production and hosting are facilitated by Elsevier B.V. This collaborative effort ensures APSB's commitment to delivering valuable contributions to the pharmaceutical sciences community.
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