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Research Article

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

Diógenes S. de Lima, Lucas E. Cardozo, Vinicius Maracaja-Coutinho, Andreas Suhrbier, Karim Mane, David Jeffries, Eduardo L. V. Silveira, Paulo P. Amaral, View ORCID ProfileRino Rappuoli, Thushan I. de Silva, and View ORCID ProfileHelder I. Nakaya
PNAS August 20, 2019 116 (34) 17121-17126; first published August 9, 2019; https://doi.org/10.1073/pnas.1822046116
Diógenes S. de Lima
aDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil;
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Lucas E. Cardozo
aDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil;
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Vinicius Maracaja-Coutinho
bAdvanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, 8380492 Santiago, Chile;
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Andreas Suhrbier
cInflammation Biology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia;
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Karim Mane
dVaccines and Immunity Theme, Medical Research Council Unit, The Gambia at LSHTM, Banjul, The Gambia;
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David Jeffries
dVaccines and Immunity Theme, Medical Research Council Unit, The Gambia at LSHTM, Banjul, The Gambia;
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Eduardo L. V. Silveira
aDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil;
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Paulo P. Amaral
eThe Gurdon Institute, University of Cambridge, CB2 1QN Cambridge, United Kingdom;
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Rino Rappuoli
fGlaxoSmithKline, 53100 Siena, Italy;
gDepartment of Infectious Diseases, Imperial College London, W12 ONN London, United Kingdom;
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  • ORCID record for Rino Rappuoli
  • For correspondence: rino.r.rappuoli@gsk.com hnakaya@usp.br
Thushan I. de Silva
dVaccines and Immunity Theme, Medical Research Council Unit, The Gambia at LSHTM, Banjul, The Gambia;
hCentre of International Child Health, Section of Paediatrics, Department of Medicine, Imperial College London, W2 1PG London, United Kingdom;
iDepartment of Infection, Immunity & Cardiovascular Disease, University of Sheffield, S10 2RX Sheffield, United Kingdom;
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Helder I. Nakaya
aDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil;
jScientific Platform Pasteur, University of São Paulo, 05508-210 São Paulo, Brazil
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  • For correspondence: rino.r.rappuoli@gsk.com hnakaya@usp.br
  1. Contributed by Rino Rappuoli, June 22, 2019 (sent for review January 15, 2019; reviewed by S. Abrignani, Petter Brodin, and Steven H. Kleinstein)

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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.

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.

  • systems biology
  • vaccination
  • transcriptome
  • long noncoding RNAs

Footnotes

  • ↵1To whom correspondence may be addressed. Email: rino.r.rappuoli{at}gsk.com or hnakaya{at}usp.br.
  • Author contributions: D.S.d.L., L.E.C., and H.I.N. designed research; D.S.d.L., L.E.C., and H.I.N. performed research; V.M.-C., A.S., K.M., D.J., E.L.V.S., P.P.A., and T.I.d.S. analyzed data; and D.S.d.L., R.R., T.I.d.S., and H.I.N. wrote the paper.

  • Reviewers: S.A., Istituto Nazionale Genetica Molecolare; P.B., Karolinska Institutet; and S.H.K., Yale University.

  • Conflict of interest statement: R.R. is a full-time employee of GlaxoSmithKline group of companies.

  • Data deposition: Raw and processed data are available in the Gene Expression Omnibus database (GSE128224).

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1822046116/-/DCSupplemental.

  • Copyright © 2019 the Author(s). Published by PNAS.

This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).

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Long noncoding RNAs are involved in multiple immunological pathways in response to vaccination
Diógenes S. de Lima, Lucas E. Cardozo, Vinicius Maracaja-Coutinho, Andreas Suhrbier, Karim Mane, David Jeffries, Eduardo L. V. Silveira, Paulo P. Amaral, Rino Rappuoli, Thushan I. de Silva, Helder I. Nakaya
Proceedings of the National Academy of Sciences Aug 2019, 116 (34) 17121-17126; DOI: 10.1073/pnas.1822046116

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Long noncoding RNAs are involved in multiple immunological pathways in response to vaccination
Diógenes S. de Lima, Lucas E. Cardozo, Vinicius Maracaja-Coutinho, Andreas Suhrbier, Karim Mane, David Jeffries, Eduardo L. V. Silveira, Paulo P. Amaral, Rino Rappuoli, Thushan I. de Silva, Helder I. Nakaya
Proceedings of the National Academy of Sciences Aug 2019, 116 (34) 17121-17126; DOI: 10.1073/pnas.1822046116
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