GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE320nnn/GSE320554/primary200OKTranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE320554GEOGSEfalseA comparative multiomic atlas of human immunity to multiple COVID-19 vaccinesThe rapid development of multiple COVID-19 vaccines, based on mRNA, recombinant adenoviral vectors and adjuvanted proteins, was critical to curtailing the global pandemic, and created a unique opportunity to compare human immunity to distinct vaccine platforms encoding the same antigen. Here, we present a longitudinal comparative analysis of innate and adaptive immune responses to the Matrix-M-adjuvanted Novavax (NX) and chimpanzee adenovirus-based AstraZeneca (AZ) vaccines in 161 healthy South African volunteers across three doses over a 11-month period collected between 2021 and 2022. Prime-boost NX vaccination (~3 weeks apart) elicited significantly stronger binding and neutralizing antibody responses than two AZ vaccine doses administered ~8 weeks apart. A NX booster administered 6–8 months later further increased the antibody titers that persisted for atleast 6 months. Both vaccines stimulated innate antiviral and inflammatory gene expression signatures within two days of vaccination. However, the strongest responses were after AZ priming and NX boosting, coinciding with plasma IFN-a and IFN-g induction, respectively, demonstrating distinct innate immune mechanisms induced by each vaccine. Transcriptional signatures of plasmablast responses that predict the magnitude of antibody responses were significantly induced 7 days after the second and booster but not primary NX vaccination, whereas these responses appeared after primary but not secondary AZ vaccination. Single-cell RNA sequencing revealed a multicellular origin of the innate transcriptional responses. Finally, a meta-analysis integrating immune responses induced by NX and AZ with those induced by the Pfizer-BioNTech mRNA vaccine demonstrated shared interferon-related signatures across all three platforms, while genes expression following mRNA vaccination was uniquely enriched in reactome pathways related to mRNA splicing, ubiquitination and proteasome processing, and class I mediated antigen presentation. Collectively, these data provide a comprehensive multiomic atlas of human immunity across three different COVID-19 vaccine platforms.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 sapiens