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TitleRBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants.
Journal, issue, pagesiScience, Vol. 25, Issue 4, Page 104043, Year 2022
Publish dateApr 15, 2022
AuthorsQingtai Liang / Yifeng Wang / Shuyuan Zhang / Jing Sun / Wenbo Sun / Jizhou Li / Yaping Liu / Mingxi Li / Lin Cheng / Yuhang Jiang / Ruoke Wang / Rui Zhang / Zihan Yang / Yifei Ren / Peng Chen / Peng Gao / Huayuan Yan / Zheng Zhang / Qi Zhang / Xuanling Shi / Jianbin Wang / Wanli Liu / Xinquan Wang / Bo Ying / Jincun Zhao / Hai Qi / Linqi Zhang /
PubMed AbstractWith the rapid emergence and spread of SARS-CoV-2 variants, development of vaccines with broad and potent protectivity has become a global priority. Here, we designed a lipid nanoparticle- ...With the rapid emergence and spread of SARS-CoV-2 variants, development of vaccines with broad and potent protectivity has become a global priority. Here, we designed a lipid nanoparticle-encapsulated, nucleoside-unmodified mRNA (mRNA-LNP) vaccine encoding the trimerized receptor-binding domain (RBD trimer) and showed its robust capability in inducing broad and protective immune responses against wild-type and major variants of concern (VOCs) in the mouse model of SARS-CoV-2 infection. The protectivity was correlated with RBD-specific B cell responses especially the long-lived plasma B cells in bone marrow, strong ability in triggering BCR clustering, and downstream signaling. Monoclonal antibodies isolated from vaccinated animals demonstrated broad and potent neutralizing activity against VOCs tested. Structure analysis of one representative antibody identified a novel epitope with a high degree of conservation among different variants. Collectively, these results demonstrate that the RBD trimer mRNA vaccine serves as a promising vaccine candidate against SARS-CoV-2 variants and beyond.
External linksiScience / PubMed:35291264 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.9 - 3.34 Å
Structure data

31624

7fjn

EMDB-31624, PDB-7fjn:
Cryo-EM structure of South African (B.1.351) SARS-CoV-2 spike glycoprotein in complex with two T6 Fab
Method: EM (single particle) / Resolution: 3.25 Å

31625

7fjo

EMDB-31625, PDB-7fjo:
Cryo-EM structure of South African (B.1.351) SARS-CoV-2 spike glycoprotein in complex with three T6 Fab
Method: EM (single particle) / Resolution: 3.34 Å

PDB-7fjs:
Crystal structure of T6 Fab bound to theSARS-CoV-2 RBD of B.1.351
Method: X-RAY DIFFRACTION / Resolution: 2.9 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
  • human immunodeficiency virus 1
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / antibody / spike / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / IMMUNE SYSTEM/VIRAL PROTEIN / IMMUNE SYSTEM-VIRAL PROTEIN complex / receptor binding / complex

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