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

Tuan  Tran, Else M. Bijker, Mariëlle C. Haks, Tom H.M. Ottenhoff, Leo Visser, Remko Schats, Pratap Venepally, Hernan Lorenzi, Peter D. Crompton, Robert W. Sauerwein

Research output: Contribution to journalArticle

Abstract

A 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.

Original languageEnglish (US)
Article number8386
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Sporozoites
Chloroquine
Plasmodium falciparum
Chemoprevention
Immunization
Malaria
Mitochondrial Proteins
Infection
Transcriptome
Natural Killer Cells
Interferons
B-Lymphocytes
Up-Regulation
Down-Regulation
Vaccines
RNA
T-Lymphocytes
Gene Expression
Genes

ASJC Scopus subject areas

  • General

Cite this

Whole-blood transcriptomic signatures induced during immunization by chloroquine prophylaxis and Plasmodium falciparum sporozoites. / Tran, Tuan ; Bijker, Else M.; Haks, Mariëlle C.; Ottenhoff, Tom H.M.; Visser, Leo; Schats, Remko; Venepally, Pratap; Lorenzi, Hernan; Crompton, Peter D.; Sauerwein, Robert W.

In: Scientific Reports, Vol. 9, No. 1, 8386, 01.12.2019.

Research output: Contribution to journalArticle

Tran, T, Bijker, EM, Haks, MC, Ottenhoff, THM, Visser, L, Schats, R, Venepally, P, Lorenzi, H, Crompton, PD & Sauerwein, RW 2019, 'Whole-blood transcriptomic signatures induced during immunization by chloroquine prophylaxis and Plasmodium falciparum sporozoites', Scientific Reports, vol. 9, no. 1, 8386. https://doi.org/10.1038/s41598-019-44924-7
Tran, Tuan  ; Bijker, Else M. ; Haks, Mariëlle C. ; Ottenhoff, Tom H.M. ; Visser, Leo ; Schats, Remko ; Venepally, Pratap ; Lorenzi, Hernan ; Crompton, Peter D. ; Sauerwein, Robert W. / Whole-blood transcriptomic signatures induced during immunization by chloroquine prophylaxis and Plasmodium falciparum sporozoites. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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