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

Abstract

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. Gene expression changes were profiled via RNAseq following the first and second dose of Ad26.COV2.S in a subset of individuals with pre-existing SARS-CoV-2 immunity due to prior SARS-CoV-2 infection, included in a randomised, double-blind, Phase 3 study (NCT#04908722). Transcriptional responses induced by a 1- and 2-dose regimen were assessed, each at two different dose levels: the marketed 5 × 10¹⁰vp dose level and a lower 1.25 × 10¹⁰vp dose level. 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. 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. This study was funded by Johnson & Johnson Innovative Medicine.