Abstract
Understanding the mechanisms of vaccine-elicited protection contributes to the development of new vaccines. The emerging field of systems vaccinology provides detailed information on host responses to vaccination and has been successfully applied to study the molecular mechanisms of several vaccines. Long noncoding RNAs (lncRNAs) are crucially involved in multiple biological processes, but their role in vaccine-induced immunity has not been explored. We performed an analysis of over 2,000 blood transcriptome samples from 17 vaccine cohorts to identify lncRNAs potentially involved with antibody responses to influenza and yellow fever vaccines. We have created an online database where all results from this analysis can be accessed easily. We found that lncRNAs participate in distinct immunological pathways related to vaccine-elicited responses. Among them, we showed that the expression of lncRNA FAM30A was high in B cells and correlates with the expression of immunoglobulin genes located in its genomic vicinity. We also identified altered expression of these lncRNAs in RNA-sequencing (RNA-seq) data from a cohort of children following immunization with intranasal live attenuated influenza vaccine, suggesting a common role across several diverse vaccines. Taken together, these findings provide evidence that lncRNAs have a significant impact on immune responses induced by vaccination.
Highlights
Contributed by Rino Rappuoli, June 22, 2019
RNA derived from these samples was hybridized onto microarrays, and raw data were deposited in the Gene Expression Omnibus (GEO) and ArrayExpress databases
To identify probes representing Long noncoding RNAs (lncRNAs), the probe sequences from each microarray platform were aligned to the human genome assembly hg38 and were reannotated based on genomic features described in GENCODE version 24
Summary
Contributed by Rino Rappuoli, June 22, 2019 We performed an analysis of over 2,000 blood transcriptome samples from 17 vaccine cohorts to identify lncRNAs potentially involved with antibody responses to influenza and yellow fever vaccines. We identified altered expression of these lncRNAs in RNA-sequencing (RNA-seq) data from a cohort of children following immunization with intranasal live attenuated influenza vaccine, suggesting a common role across several diverse vaccines. The emerging field of systems vaccinology provides substantial new insights and a new tool for testing and developing vaccines [2] This approach has been applied to the study of immune responses induced by yellow fever vaccination [3,4,5], influenza vaccination [6,7,8,9,10,11,12,13], malaria [14], and herpes zoster vaccination [15] among others. Our findings reveal the potential roles of lncRNAs in regulating the immune responses to vaccination
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