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The effect of inhaled IFNbeta (SNG001) versus placebo on peripheral blood mononuclear cells during an upper respiratory tract infection

ABSTRACT: Microarray analysis of whole blood samples (collected into PAXgene tubes from PreAnalytiX) during a phase II double-blind, randomized (1:1 ratio) clinical trial in which inhaled IFN-β (SNG001) or placebo treatment was initiated within 24 hours of asthmatics reporting cold symptoms. Patients were dosed once a day for 14 days, with samples collected at day 1 (prior to first dose), day 4 and day 7. Analysis of genome-wide gene expression (only conducted using samples from the BTS Step 4/5, mITT subgroup), showed a treatment-related enhancement of systemic innate immunity, thereby providing compelling evidence for exogenous IFN-β enhancing antiviral responses.

ORGANISM(S): Homo sapiens

PROVIDER: GSE50943 | GEO | 2014/06/30

SECONDARY ACCESSION(S): PRJNA219407

REPOSITORIES: GEO

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Project description:Background: Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population. Methods: We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-γ ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis. Results: One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-γ ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A. Conclusion: The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies. Trial registration: ClinicalTrials.gov number NCT00953927 Whole blood collected 1 day post-vaccination with MVA85A or Candin placebo (82 samples)

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The effect of inhaled IFNbeta (SNG001) versus placebo on peripheral blood mononuclear cells during an upper respiratory tract infection

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