Whole-blood transcriptomic signatures induced during immunization by chloroquine prophylaxis and Plasmodium falciparum sporozoites

dc.contributor.authorTran, Tuan M.
dc.contributor.authorBijker, Else M.
dc.contributor.authorHaks, Mariëlle C.
dc.contributor.authorOttenhoff, Tom H. M.
dc.contributor.authorVisser, Leo
dc.contributor.authorSchats, Remko
dc.contributor.authorVenepally, Pratap
dc.contributor.authorLorenzi, Hernan
dc.contributor.authorCrompton, Peter D.
dc.contributor.authorSauerwein, Robert W.
dc.contributor.departmentMedicine, School of Medicineen_US
dc.date.accessioned2019-08-27T12:41:14Z
dc.date.available2019-08-27T12:41:14Z
dc.date.issued2019-06-10
dc.description.abstractA highly effective vaccine that confers sterile protection to malaria is urgently needed. Immunization under chemoprophylaxis with sporozoites (CPS) consistently confers high levels of protection in the Controlled Human Malaria infection (CHMI) model. To provide a broad, unbiased assessment of the composition and kinetics of direct ex vivo human immune responses to CPS, we profiled whole-blood transcriptomes by RNA-seq before and during CPS immunization and following CHMI challenge. Differential expression of genes enriched in modules related to T cells, NK cells, protein synthesis, and mitochondrial processes were detected in fully protected individuals four weeks after the first immunization. Non-protected individuals demonstrated transcriptomic changes after the third immunization and the day of treatment, with upregulation of interferon and innate inflammatory genes and downregulation of B-cell signatures. Protected individuals demonstrated more significant interactions between blood transcription modules compared to non-protected individuals several weeks after the second and third immunizations. These data provide insight into the molecular and cellular basis of CPS-induced immune protection from P. falciparum infection.en_US
dc.identifier.citationTran, T. M., Bijker, E. M., Haks, M. C., Ottenhoff, T., Visser, L., Schats, R., … Sauerwein, R. W. (2019). Whole-blood transcriptomic signatures induced during immunization by chloroquine prophylaxis and Plasmodium falciparum sporozoites. Scientific reports, 9(1), 8386. doi:10.1038/s41598-019-44924-7en_US
dc.identifier.urihttps://hdl.handle.net/1805/20592
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.relation.isversionof10.1038/s41598-019-44924-7en_US
dc.relation.journalScientific Reportsen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/us*
dc.sourcePMCen_US
dc.subjectPredictive markersen_US
dc.subjectMalariaen_US
dc.titleWhole-blood transcriptomic signatures induced during immunization by chloroquine prophylaxis and Plasmodium falciparum sporozoitesen_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
41598_2019_Article_44924.pdf
Size:
7.35 MB
Format:
Adobe Portable Document Format
Description:
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.99 KB
Format:
Item-specific license agreed upon to submission
Description: