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TitlePreclinical evaluation of RQ3013, a broad-spectrum mRNA vaccine against SARS-CoV-2 variants.
Journal, issue, pagesSci Bull (Beijing), Vol. 68, Issue 24, Page 3192-3206, Year 2023
Publish dateDec 30, 2023
AuthorsShudan Tan / Jinghua Zhao / Xue Hu / Yufeng Li / Zihan Wu / Guoliang Lu / Zhaoli Yu / Binhe Du / Yan Liu / Li Li / Yuchen Chen / Ye Li / Yanfeng Yao / Xiaoyu Zhang / Juhong Rao / Ge Gao / Yun Peng / Hang Liu / Zhiming Yuan / Jia Liu / Qianran Wang / Hengrui Hu / Xiaobo Gao / Hui Zhou / Hang Yu / Yingjie Xu / Wei Yu / Lin Feng / Manli Wang / Chao Shan / Jing Lu / Jinzhong Lin /
PubMed AbstractThe global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines ...The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines to combat COVID-19. Here we report the preclinical development of RQ3013, an mRNA vaccine candidate intended to bring broad protection against SARS-CoV-2 variants of concern (VOCs). RQ3013, which contains pseudouridine-modified mRNAs formulated in lipid nanoparticles, encodes the spike (S) protein harboring a combination of mutations responsible for immune evasion of VOCs. Here we characterized the expressed S immunogen and evaluated the immunogenicity, efficacy, and safety of RQ3013 in various animal models. RQ3013 elicited robust immune responses in mice, hamsters, and nonhuman primates (NHP). It can induce high titers of antibodies with broad cross-neutralizing ability against the wild-type, B.1.1.7, B.1.351, B.1.617.2, and the newly emerging Omicron variants. In mice and NHP, two doses of RQ3013 protected the upper and lower respiratory tract against infection by SARS-CoV-2 and its variants. Furthermore, our safety assessment of RQ3013 in NHP showed no observable adverse effects. These results provide strong support for the evaluation of RQ3013 in clinical trials and suggest that it may be a promising candidate for broad protection against COVID-19 and its variants.
External linksSci Bull (Beijing) / PubMed:37993332
MethodsEM (single particle)
Resolution3.5 - 3.9 Å
Structure data

33346

7xoe

EMDB-33346, PDB-7xoe:
Cryo-EM structure of S glycoprotein encoded by the Covid-19 mRNA vaccine candidate RQ3013 (Prefusion state)
Method: EM (single particle) / Resolution: 3.9 Å

33347

7xog

EMDB-33347, PDB-7xog:
Cryo-EM structure of S glycoprotein encoded by the Covid-19 mRNA vaccine candidate RQ3013 (Postfusion state)
Method: EM (single particle) / Resolution: 3.5 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-MAN:
alpha-D-mannopyranose / Mannose

Source
  • severe acute respiratory syndrome coronavirus
  • synthetic construct (others)
KeywordsVIRAL PROTEIN / Spike / mRNA vaccine / SARS-CoV-2 / S clycoprotein

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