机构:[1]Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China[2]University of Chinese Academy of Sciences, Beijing, China[3]KeyLaboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming,Yunnan, China[4]Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China[5]Institute for Hepatology, National Clinical Research Center forInfectious Disease, Shenzhen Third People’s Hospital, Shenzhen, Guangdong Province, China[6]State Key Laboratory of Respiratory Disease, Guangzhou Institute of RespiratoryHealth, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China[7]LivzonBio, Inc., Zhuhai, Guangdong, China[8]School of PharmaceuticalSciences, Tsinghua University, Beijing, China[9]Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China[10]Kunming National High-level Biosafety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy ofSciences, Kunming, Yunnan, China[11]Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA[12]Bioland Laboratory (Guangzhou RegenerativeMedicine and Health Guangdong Laboratory), and Guangzhou Laboratory, Guangzhou, China
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19.
基金:
National Key R&D Program of China (2018ZX10301-404 to
HP), the Emergency Key Program of Guangzhou Laboratory (EKPG21-21 to HP), and
Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory to HP).
第一作者机构:[1]Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China[2]University of Chinese Academy of Sciences, Beijing, China
共同第一作者:
通讯作者:
通讯机构:[1]Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China[3]KeyLaboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming,Yunnan, China[10]Kunming National High-level Biosafety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy ofSciences, Kunming, Yunnan, China[12]Bioland Laboratory (Guangzhou RegenerativeMedicine and Health Guangdong Laboratory), and Guangzhou Laboratory, Guangzhou, China
推荐引用方式(GB/T 7714):
Sun Shiyu,Cai Yueqi,Song Tian-Zhang,et al.Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2[J].CELL RESEARCH.2021,31(9):1011-1023.doi:10.1038/s41422-021-00531-8.
APA:
Sun, Shiyu,Cai, Yueqi,Song, Tian-Zhang,Pu, Yang,Cheng, Lin...&Peng, Hua.(2021).Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2.CELL RESEARCH,31,(9)
MLA:
Sun, Shiyu,et al."Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2".CELL RESEARCH 31..9(2021):1011-1023