Early transcriptional responses following Ad26.COV2.S vaccination in individuals with prior SARS-CoV-2 infection

BACKGROUND: Ad26.COV2.S is a recombinant, replication-incompetent human adenovirus serotype 26 (Ad26) vectored vaccine encoding a full-length SARS-CoV-2 spike protein in a prefusion-stabilised conformation. The genes and pathways which are differentially regulated following vaccination with Ad26.COV2.S, how these differ over time, and under different regimens, have not been investigated. METHODS: vp dose level. FINDINGS: Consistent with other vaccine studies, antiviral, interferon, cytokine, and monocyte blood transcriptional modules were differentially regulated one day post-Ad26.COV2.S vaccination. At three days post-vaccination, innate immunity was still transcriptionally active at lower levels than one day post-vaccination. By seven days post-Ad26.COV2.S, increased immunoglobulin gene expression dominated the transcriptome response, indicating a shift towards humoural and B cell responses and activation of adaptive immunity. Transcriptional responses post-Ad26.COV2.S were generally stronger after the first dose versus the second dose. INTERPRETATION: In this study in whole blood, innate and adaptive immune transcripts were upregulated as early as one and seven days post-Ad26.COV2.S, respectively. These findings add to the limited data on innate immune responses to adenovirus-based vaccines in a clinical setting and contribute to understanding the mechanisms behind the adaptive immune responses that may contribute to protective immunity. FUNDING: This study was funded by Johnson & Johnson Innovative Medicine.