Early transcriptomic responses to TB vaccine ID93 + GLA-SE (TBVPX-203)

ID93+GLA-SE is a candidate subunit vaccine that will soon be evaluated in a Phase 2b efficacy trial for prevention of recurrent TB among patients undergoing TB treatment. Though the vaccine regimen was shown to elicit robust CD4+ T cell and IgG antibody responses in a clinical trial among recently treated TB patients (TBVPX-203), the mechanisms underlying the development of these responses is not well understood. In this study we used specimens from TBVPX-203 participants to describe the changes in peripheral blood gene expression that occur after ID93+GLA-SE vaccination. Analyses revealed several distinct modules of covarying genes that were either up- or down-regulated after vaccination, including genes associated with innate immune pathways at 3 days post-vaccination and genes associated with lymphocyte expansion and B cell activation at 7 days post-vaccination. Notably, the regulation of these gene modules was affected by the dose schedule and participant sex. The results provide insight into the complex interplay of the innate and adaptive arms of the immune system in developing responses to vaccination with ID93+GLA-SE and demonstrate how dosing and schedule can affect vaccine responses.