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TitleLineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine.
Journal, issue, pagesCell Host Microbe, Vol. 30, Issue 12, Page 1732-11744.e7, Year 2022
Publish dateDec 14, 2022
AuthorsYangtao Wu / Shaojuan Wang / Yali Zhang / Lunzhi Yuan / Qingbing Zheng / Min Wei / Yang Shi / Zikang Wang / Jian Ma / Kai Wang / Meifeng Nie / Jin Xiao / Zehong Huang / Peiwen Chen / Huilin Guo / Miaolin Lan / Jingjing Xu / Wangheng Hou / Yunda Hong / Dabing Chen / Hui Sun / Hualong Xiong / Ming Zhou / Che Liu / Wenjie Guo / Huiyu Guo / Jiahua Gao / Congling Gan / Zhixiong Li / Haitao Zhang / Xinrui Wang / Shaowei Li / Tong Cheng / Qinjian Zhao / Yixin Chen / Ting Wu / Tianying Zhang / Jun Zhang / Hua Cao / Huachen Zhu / Quan Yuan / Yi Guan / Ningshao Xia /
PubMed AbstractSARS-CoV-2 spread in humans results in continuous emergence of new variants, highlighting the need for vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation-patch ...SARS-CoV-2 spread in humans results in continuous emergence of new variants, highlighting the need for vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation-patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x) that contains key regions and residues across multiple SAR-CoV-2 variants. STFK1628x demonstrated high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine composed of STFK and STFK1628x elicited high titers of broad-spectrum neutralizing antibodies to 19 circulating SARS-CoV-2 variants, including Omicron sublineages BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5. Furthermore, this vaccine conferred robust protection against intranasal challenges by either SARS-CoV-2 ancestral strain or immune-evasive Beta and Omicron BA.1. Strikingly, vaccination with the bivalent vaccine in hamsters effectively blocked within-cage virus transmission of ancestral SARS-CoV-2, Beta variant, and Omicron BA.1 to unvaccinated sentinels. Thus, our study provided insight and antigen candidates for the development of next-generation COVID-19 vaccines.
External linksCell Host Microbe / PubMed:36323313 / PubMed Central
MethodsEM (single particle)
Resolution3.81 - 3.88 Å
Structure data

32676

7wp6

EMDB-32676, PDB-7wp6:
Cryo-EM structure of SARS-CoV-2 recombinant spike protein STFK in complex with three neutralizing antibodies
Method: EM (single particle) / Resolution: 3.81 Å

32678

7wp8

EMDB-32678, PDB-7wp8:
Cryo-EM structure of SARS-CoV-2 recombinant spike protein STFK1628x in complex with three neutralizing antibodies
Method: EM (single particle) / Resolution: 3.88 Å

Chemicals

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

Source
  • mus musculus (house mouse)
  • severe acute respiratory syndrome coronavirus 2
KeywordsIMMUNE SYSTEM/VIRAL PROTEIN / SARS-CoV-2 / spike / vaccine / neutralizing antibody / Cryo-EM / VIRAL PROTEIN / IMMUNE SYSTEM-VIRAL PROTEIN complex

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