Gene signatures related to B-cell proliferation predict influenza vaccine-induced antibody response.
Vaccines are very effective at preventing infectious disease but not all recipients mount a protective immune response to vaccination. Recently, gene expression profiles of PBMC samples in vaccinated individuals have been used to predict the development of protective immunity. However, the magnitude of change in gene expression that separates vaccine responders and nonresponders is likely to be small and distributed across networks of genes, making the selection of predictive and biologically relevant genes difficult. Here we apply a new approach to predicting vaccine response based on coordinated upregulation of sets of biologically informative genes in postvaccination gene expression profiles. We found that enrichment of gene sets related to proliferation and immunoglobulin genes accurately segregated high responders to influenza vaccination from low responders and achieved a prediction accuracy of 88% in an independent clinical trial. Many of the genes in these gene sets would not have been identified using conventional, single-gene level approaches because of their subtle upregulation in vaccine responders. Our results demonstrate that gene set enrichment method can capture subtle transcriptional changes and may be a generally useful approach for developing and interpreting predictive models of the human immune response.
|Year of Publication
Eur J Immunol
|PubMed Central ID
R37 AI048638 / AI / NIAID NIH HHS / United States
R01AI091493 / AI / NIAID NIH HHS / United States
U19 AI090023 / AI / NIAID NIH HHS / United States
U19AI090023 / AI / NIAID NIH HHS / United States
P51 OD011132 / OD / NIH HHS / United States
U19 AI057266 / AI / NIAID NIH HHS / United States
R56 AI048638 / AI / NIAID NIH HHS / United States
R01 AI091493 / AI / NIAID NIH HHS / United States
R37 DK057665 / DK / NIDDK NIH HHS / United States
R01 CA121941 / CA / NCI NIH HHS / United States