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

ABSTRACT: 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. 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. We profiled 44 PBMC samples from 22 individuals receiving either AZ or NX, collected at baseline, and at 1 and 7 days after primary, secondary or booster doses. After pre-processing and quality control, which included removal of one sample (AZ, secondary day 1) due to low-quality cells, we obtained 162,037 high quality transcriptomes. No significant differences in frequency were observed after vaccination or between groups, but there were significant induction of interferon-stimulated gene expression early after vaccination. At baseline, myeloid cell clusters (CD14+ monocytes, CD16+ monocytes and cDC2) expressed these genes at higher magnitudes than other cell types. After primary NX vaccination, no cell type showed increased expression of these modules, consistent with bulk RNAseq, which revealed induction only at day 2. In contrast, primary AZ vaccination led to a striking upregulation of ISGs across all cell types at day 1. After NX boosting, CD16+ monocytes and several other cell types showed modest ISG induction, whereas secondary AZ vaccination elicited no induction of these responses.

ORGANISM(S): Homo sapiens

PROVIDER: GSE318946 | GEO | 2026/08/12

REPOSITORIES: GEO