SARS-CoV-2 vaccine ChAdOx1 nCoV-19 infection of human cell lines reveals low levels of viral backbone gene transcription alongside very high levels of SARS-CoV-2 S glycoprotein gene transcription

Abstract Background ChAdOx1 nCoV-19 is a recombinant adenovirus vaccine against SARS-CoV-2 that has passed phase III clinical trials and now in use across the globe. Although replication-defective normal cells, 28 kbp of genes delivered to cell nucleus alongside S glycoprotein gene. Methods We used direct RNA sequencing analyse transcript expression from genome human MRC-5 A549 lines are non-permissive for vector replication permissive line, HEK293. In addition, we quantitative proteomics study over time proteome phosphoproteome MRC5 cells infected with vaccine. Results The expected coding dominated all lines. also detected rare transcripts aberrant splice patterns or polyadenylation site usage. Adenovirus were almost absent but there was broader repertoire adenoviral gene at very low levels. Proteomically, addition glycoprotein, multiple proteins compared just one cells. Conclusions Overall, vaccine’s transcriptomic proteomic culture as expected. combined approaches provide detailed insight into behaviour this important class using state-of-the-art techniques illustrate potential technique inform future viral design.