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bioRxiv · 10.1101/2024.06.21.600005

Molecular basis of Ad5-nCoV Vaccine-Induced Immunogenicity

Dong, D.·Song, Y.·Wu, S.·Wu, B.·Peng, C.·Kong, W.·Zhang, Z.·Hou, L.·Li, S.
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Abstract

In response to coronavirus disease 2019 (COVID-19), numerous vaccines have been developed to protect against SARS-CoV-2 infection. Ad5-nCoV (Convidecia) is a vaccine listed for emergency use by the WHO and has been administrated to millions of people globally. It comprises a series of human adenovirus 5 (Ad5) replication-incompetent vectored vaccines that transduce the spike protein (S) gene of various SARS-CoV-2 strains. Despite promising clinical data demonstrating its safety and effectiveness, the underlying molecular mechanism of its high immunogenicity and incidence of adverse reactions remains less understood. Here we combined cryo-ET, fluorescence microscopy and mass spectrometry to characterize the in situ structures, density and site-specific glycan compositions of the Ad5-nCoV_Wu and Ad5-nCoV_O vaccine-induced S antigens, which encode the unmodified SARS-CoV-2 Wuhan-Hu-1 S gene and optimized Omicron S gene, respectively. We found that the vaccine-induced S are structurally intact, antigenic and densely distributed on the cell membrane. Compared to Ad5-nCoV_Wu induced S, the Ad5-nCoV_O induced S demonstrate significantly better stability and is less likely to induce syncytia among inoculated cells. Our work demonstrated that Ad5-nCoV is a prominent platform for antigen induction and cryo-ET can be a useful technique for vaccine characterization and development.

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Dong, D., Song, Y., Wu, S., Wu, B., Peng, C., Kong, W., Zhang, Z., Hou, L., Li, S.. 2024-06-21. Molecular basis of Ad5-nCoV Vaccine-Induced Immunogenicity. https://doi.org/10.1101/2024.06.21.600005

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