Transcriptome analysis and safety profile of the early-phase clinical response to an adjuvanted grass allergoid immunotherapy.

backgroundSpecific immunotherapy is the only type of disease-modifying treatment, which induces rapid desensitization and long-term sustained unresponsiveness in patients with seasonal allergic rhinoconjunctivitis. The safety and tolerability of a new cumulative dose regimen of 35600 SU Grass MATA MPL for subcutaneous immunotherapy were assessed in pre-seasonal, single-blind, placebo controlled Phase I clinical study. Underlying immunological mechanisms were explored using transcriptome analysis of peripheral blood mononuclear cells.

methodsStudy subjects with a history of moderate to severe seasonal allergic rhinitis and/or conjunctivitis (SAR) due to grass (

resultsThe results of the study indicated that the higher cumulative dose regimen of the immunotherapy was well-tolerated. Changes in gene expression profile were associated with early immune responses implicating innate and adaptive immune mechanisms. Pathways and mechanistic network analysis via IPA mapped differentially expressed genes onto canonical pathways related to T cell differentiation, cytokine signalling and Th1/Th2 activation pathways. The transcriptome findings of the study could be further verified in large-scale field studies in order to explore their potential as predictive markers of successful immunotherapy.

conclusionsThe higher dose cumulative regime 35600 SU of Grass MATA MPL vaccine was well tolerated and safe. Molecular markers IL-27, IL-10, IL-4, TNF, IFNγ, TGFβ and TLR4 were the main predicted molecular drivers of the observed gene expression changes following early stages of SIT with Grass MATA MPL immunotherapy.