Transcriptomic profiling of human peripheral blood samples collected three days or two weeks after the primary RV144 ALVAC/gp120 vaccine series

We previously showed in NHP studies that a protective gene signature that was enriched in uninfected monkeys after Ad26/gp140 vaccination also associated with higher magnitude of ADCP (Ehrenberg et al., 2019). In the RV144 human trial a number of immunological parameters were previously measured as part of the immune-correlates analysis, but not ADCP. The RV306 immunogenicity trial that employed a similar prime boost RV144 vaccine regimen with additional late boosts provided us with a unique opportunity to test if the gene signature was associated with ADCP (Pitisuttithum et al., 2020). We generated transcriptome-wide gene expression data from peripheral blood two weeks after the RV144 vaccine regimen (prior to the additional boosts) and assessed for enrichment of the gene signature with the magnitude of ADCP measured at the same timepoint in 24 participants. The gene signature with 118 enriched genes was significantly associated with higher magnitude of ADCP (NES=3.0, P<0.001). Using the same geneset, 93 genes were found to be enriched in a subset of overlapping participants (N=21), where samples were collected 3 days after the RV144 immunizations (NES=2.5, P<0.001). Overall design: The RV306 vaccine trial was conducted in Thailand and all participants received the primary RV144 ALVAC/gp120 vaccine series, with additional late boosts assigned to specific groups (Pitisuttithum et al., 2020). Bulk RNA-seq was performed in 24 participants two weeks after the RV144 vaccine regimen (week 26). Additionally, RNA-seq was also performed 3 days after the same primary endpoint in a subset of the participants (N =21).