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Omics · study · 2026

A comparative multiomic atlas of human immunity to multiple COVID-19 vaccines

Listed in NCBI GEO

The 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.

Description

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.

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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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Expression profiling by high throughput sequencing · Homo sapiens
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Life Sciences
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Longitudinal study 65% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%

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Provenance · 1 source records, 11 field assertions
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