Long noncoding RNAs are involved in multiple immunological pathways in response to vaccination

Significance Long noncoding RNAs (lncRNAs) are known to be involved in several immunological processes. In spite of their general relevance to human immunity, to date there are no reports on the importance of lncRNAs in vaccine responses. Here we apply a “systems vaccinology” framework to study the role of lncRNAs in vaccine-mediated immunity. We applied meta-analytical approaches using public microarray data from over 2,000 blood transcriptome samples of vaccinees and an RNA-sequencing (RNA-seq) dataset from vaccinated children to tackle this question. Our results indicate that lncRNAs are important players in several immunological processes elicited by vaccination. 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.

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