Transcriptome-wide changes in gene expression, splicing, and lncRNAs in response to a live attenuated dengue virus vaccine

Eun Young Kim, Yan Che, Hansi J. Dean, Ramon Lorenzo-Redondo, Michael Stewart, Caroline K. Keller, Daniel Whorf, Dawson Mills, Nikita N. Dulin, Tiffany Kim, Megan Votoupal, Miriam Walter, Ana Fernandez-Sesma, Heejin Kim, Steven M. Wolinsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The tetravalent dengue vaccine candidate, TAK-003, induces a functional antibody response, but the titers of antibodies against the four serotypes of the dengue virus (DENV) can vary. Here, through a transcriptomic analysis on whole blood collected from recipients of a two-dose schedule of TAK-003, we examine gene expression, splicing, and transcript isoform-level changes for both protein-coding and noncoding genes to broaden our understanding of the immune response. Our analysis reveals a dynamic pattern of vaccine-associated regulation of long noncoding RNAs (lncRNAs), differential splicing of interferon-stimulated gene exons, and gene expression changes related to multiple signaling pathways that detect viral infection. Co-expression networks isolate immune cell-type-related and interferon-response modules that represent specific biological processes that correlate with more robust antibody responses. These data provide insights into the early determinants of the variable immune response to the vaccine, highlighting the significance of splicing and isoform-level gene regulatory mechanisms in defining vaccine immunogenicity.

Original languageEnglish (US)
Article number110341
JournalCell reports
Volume38
Issue number6
DOIs
StatePublished - Feb 8 2022

Keywords

  • gene correlation networks
  • live attenuated dengue virus vaccine
  • long noncoding RNA
  • modular transcriptional repertoire
  • splicing
  • transcriptome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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