The Immune Signatures Data Resource: A compendium of systems vaccinology datasets

Abstract

Vaccines are among the most cost-effective public health interventions for preventing infection-induced morbidity and mortality, yet much remains to be learned regarding the mechanisms by which vaccines protect. Systems immunology combines traditional immunology with modern ‘omic profiling techniques and computational modeling to promote rapid and transformative advances in vaccinology and vaccine discovery. The NIH/NIAID Human Immunology Project Consortium (HIPC) has leveraged systems immunology approaches to identify molecular signatures associated with the immunogenicity of many vaccines, including those targeting seasonal influenza, yellow fever, and hepatitis B. These data are made available to the broader scientific community through the ImmuneSpace data portal and analysis engine leveraging the NIH/NIAID ImmPort repository1,2. However, a barrier to progress in this area is that comparative analyses have been limited by the distributed nature of some data, potential batch effects across studies, and the absence of multiple relevant studies from non-HIPC groups in ImmPort. To support comparative analyses across different vaccines, we have created the Immune Signatures Data Resource, a compendium of standardized systems vaccinology datasets. This data resource is available through ImmuneSpace, along with code to reproduce the processing and batch normalization starting from the underlying study data in ImmPort and the Gene Expression Omnibus (GEO). The current release comprises 1405 participants from 53 cohorts profiling the response to 24 different vaccines and includes transcriptional profiles and antibody response measurements. This novel systems vaccinology data release represents a valuable resource for comparative and meta-analyses that will accelerate our understanding of mechanisms underlying vaccine responses.

Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses

“…These datasets were compiled into ImmPort , an NIH-funded repository for immunological data 27 , and uploaded to ImmuneSpace (http://www.ImmuneSpace.org) for centralized QC and processing (Figure 1A). This combined database, named the Immune Signatures Data Resource 26 , includes responses to a broad range of vaccines, including live-attenuated viruses (e.g. yellow fever, smallpox and influenza vaccines), recombinant viral vectors (e.g.…”

“…Here, we have demonstrated that meta-analysis of vaccine trials can provide valuable insights into the common and unique aspects of immune responses across vaccines. Combined with the Immune Signatures Data Resource 26 , these computational approaches and repositories will enable future research into the mechanisms of vaccine-induced immunity to inform development of improved adjuvants and vaccines.…”

“…An extensive description of the across studies normalization used to correct for batch effects can be found in the Immune Signatures Data Resource manuscript 26 . Briefly, a linear model was fit using the pre-vaccination normalized gene expression as a dependent variable and platform, study, and blood sample type (i.e., whole blood or PBMC) as independent variables.…”

“…An extensive description of the preprocessing of microarray and RNA-Sequencing (RNA-Seq) datasets included in the Immune Signatures Data Resource can be found in the associated manuscript 26 . The dataset includes 2,949 samples from published studies and 228 samples not included in previously published studies.…”

“…Here we leverage Immune Signatures Data Resource 26 , a curated database of publicly available datasets containing transcriptional and immune response profiling of peripheral blood following vaccination in humans, to perform a comparative analysis of transcriptional responses from 820 healthy young adults across 13 different vaccines. We find that while a common transcriptional program is shared across many vaccines, there is significant heterogeneity especially in the kinetics of immune responses.…”