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TitleMolecular basis of Ad5-nCoV vaccine-induced immunogenicity.
Journal, issue, pagesStructure, Vol. 33, Issue 5, Page 858-868.e5, Year 2025
Publish dateMay 1, 2025
AuthorsDongyang Dong / Yutong Song / Shipo Wu / Busen Wang / Cheng Peng / Weiping Zhang / Weizheng Kong / Zheyuan Zhang / Jingwen Song / Li-Hua Hou / Sai Li /
PubMed AbstractAd5-nCoV (Convidecia) is listed for emergency use against COVID-19 by the World Health Organization (WHO) and has been globally administered to millions of people. It utilizes human adenovirus 5 (Ad5) ...Ad5-nCoV (Convidecia) is listed for emergency use against COVID-19 by the World Health Organization (WHO) and has been globally administered to millions of people. It utilizes human adenovirus 5 (Ad5) replication-incompetent vector to deliver the spike (S) protein gene from various SARS-CoV-2 strains. Despite promising clinical data, the molecular mechanism underlying its high immunogenicity and adverse reactions remain incompletely understood. Here, we primarily applied cryo-electron tomography (cryo-ET), fluorescence microscopy and mass spectrometry to analyze the Ad5-nCoV_Wu and Ad5-nCoV_O vaccine-induced S antigens. These antigens encode the unmodified SARS-CoV-2 Wuhan-Hu-1 S gene and the stabilized Omicron S gene, respectively. Our findings highlight the structural integrity, antigenicity, and dense distribution on cell membrane of the vaccine-induced S proteins. Ad5-nCoV_O induced S proteins exhibit improved stability and reduced syncytia formation among inoculated cells. Our work demonstrates that Ad5-nCoV is a prominent platform for antigen induction and cryo-ET can be a useful technique for vaccine characterization and development.
External linksStructure / PubMed:40112804
MethodsEM (subtomogram averaging)
Resolution15.0 - 22.0 Å
Structure data

EMDB-60599: SARS-CoV-2 spike (Wuhan-Hu-1) in the closed conformation induced by Ad5-nCoV vaccine
Method: EM (subtomogram averaging) / Resolution: 18.0 Å

EMDB-60600: SARS-CoV-2 spike (Wuhan-Hu-1) in the One-RBD-up conformation induced by Ad5-nCoV vaccine
Method: EM (subtomogram averaging) / Resolution: 22.0 Å

EMDB-60601: SARS-CoV-2 spike (Omicron) in the closed conformation induced by Ad5-nCoV vaccine
Method: EM (subtomogram averaging) / Resolution: 16.0 Å

EMDB-60602: SARS-CoV-2 spike (Omicron) in the One-RBD-up conformation induced by Ad5-nCoV vaccine
Method: EM (subtomogram averaging) / Resolution: 15.0 Å

Source
  • Severe acute respiratory syndrome coronavirus 2

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