机构：[1]State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China.[2]Guangzhou Laboratory, Guangzhou 510000, China.[3]Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research, Guangdong Lewwin Pharmaceutical Research Institute Co., Ltd., Guangdong Engineering Research Center for Innovative Drug Evaluation and Research, Guangzhou 510000, China.[4]Division of Life Science, Center for Cancer Research, and State Key Laboratory for Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China.[5]Argorna Pharmaceuticals Co., Ltd., Guangzhou 510000, China.[6]Guangzhou RiboBio Co., Ltd., Guangzhou 510000, China.[7]Technology Centre, Guangzhou Customs, Guangzhou 510000, China.[8]State Key Laboratory of Respiratory Disease, Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510000, China.[9]Guangzhou Key Laboratory for Clinical Rapid Diagnosis and Early Warning of Infectious Diseases, Guangzhou 510000, China.[10]State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa 519020, Macau (SAR), China.
There is an urgent need for a broad-spectrum and protective vaccine due to the emergence and rapid spreading of more contagious SARS-CoV-2 strains. We report the development of RBMRNA-176, a pseudouridine (Ψ) nucleoside-modified mRNA-LNP vaccine encoding pre-fusion stabilized trimeric SARS-CoV-2 spike protein ectodomain, and evaluate its immunogenicity and protection against virus challenge in mice and nonhuman primates. A prime-boost immunization with RBMRNA-176 at intervals of 21 days resulted in high IgG titers (over 1:819,000 endpoint dilution) and a CD4+ Th1-biased immune response in mice. RBMRNA-176 vaccination induced pseudovirus-neutralizing antibodies with IC50 ranging from 1:1020 to 1:2894 against SARS-CoV-2 spike pseudotyped wild-type and variant viruses, including Alpha, Beta, Gamma, and Kappa. Moreover, significant control of viral replication and histopathology in lungs was observed in vaccinated mice. In nonhuman primates, a boost given by RBMRNA-176 on day 21 after the prime induced a persistent and sustained IgG response. RBMRNA-176 vaccination also protected macaques against upper and lower respiratory tract infection, as well as lung injury. Altogether, these findings support RBMRNA-176 as a vaccine candidate for prevention of COVID-19.
基金：
This work was funded by the National Natural Science Foundation of China (82174053,
82141201, 82141206, 82151210, 82174333, 81872765), the Emergency Key Program of Guangzhou
Laboratory (EKPG21-06, EKPG21-22), the Guangdong Provincial Research Project for Prevention
and Treatment of SARS-CoV-2 (2021A1111090003), the Guangdong Key Research and Development Plan (No.2022B1111020002), the Traditional Chinese Medicine Bureau of Guangdong Province
(20211178), the Guangdong Provincial Department of Natural Resources project (GDNRC [2021]51),
the Key Program “New Drug Creation” of Guangdong Key Research and Development Plan
(No.2019B020202001), the Macao Science and Technology Development Fund (0022/2021/A1), the
Guangzhou Science and technology planning project (202102100003), the Guangzhou Fundamental
and Application Foundation Research Project (202102020984), and the Youth Lift Project of China Association for Science and Technology (2020-2022QNRC002).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|3 区医学
小类|4 区免疫学4 区医学：研究与实验
最新[2025]版：
大类|3 区医学
小类|3 区免疫学3 区医学：研究与实验
第一作者：
第一作者机构：[1]State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China.[2]Guangzhou Laboratory, Guangzhou 510000, China.
共同第一作者：
通讯作者：
通讯机构：[1]State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China.[2]Guangzhou Laboratory, Guangzhou 510000, China.[3]Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research, Guangdong Lewwin Pharmaceutical Research Institute Co., Ltd., Guangdong Engineering Research Center for Innovative Drug Evaluation and Research, Guangzhou 510000, China.[4]Division of Life Science, Center for Cancer Research, and State Key Laboratory for Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China.[5]Argorna Pharmaceuticals Co., Ltd., Guangzhou 510000, China.[8]State Key Laboratory of Respiratory Disease, Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510000, China.[9]Guangzhou Key Laboratory for Clinical Rapid Diagnosis and Early Warning of Infectious Diseases, Guangzhou 510000, China.[10]State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa 519020, Macau (SAR), China.
推荐引用方式(GB/T 7714)：
Ma Qinhai,Li Runfeng,Guo Jianmin,et al.Immunization with a Prefusion SARS-CoV-2 Spike Protein Vaccine (RBMRNA-176) Protects against Viral Challenge in Mice and Nonhuman Primates[J].Vaccines.2022,10(10):doi:10.3390/vaccines10101698.
APA：
Ma Qinhai,Li Runfeng,Guo Jianmin,Li Man,Ma Lin...&Yang Zifeng.(2022).Immunization with a Prefusion SARS-CoV-2 Spike Protein Vaccine (RBMRNA-176) Protects against Viral Challenge in Mice and Nonhuman Primates.Vaccines,10,(10)
MLA：
Ma Qinhai,et al."Immunization with a Prefusion SARS-CoV-2 Spike Protein Vaccine (RBMRNA-176) Protects against Viral Challenge in Mice and Nonhuman Primates".Vaccines 10..10(2022)
