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| Status |
Public on Jun 05, 2021 |
| Title |
A baseline transcriptional signature associates with clinical malaria risk in RTS,S/AS01-vaccinated African children |
| Organisms |
Homo sapiens; blank sample |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
In a phase 3 trial in African infants/children, the RTS,S/AS01 (GSK) vaccine showed moderate efficacy against clinical malaria. We aimed to identify RTS,S/AS01-induced signatures associated with clinical malaria by analyzing antigen-stimulated peripheral blood mononuclear cells sampled from a subset of trial participants at baseline and month 3 (one month post-final dose). RTS,S/AS01 vaccination was associated with downregulation of B-cell and monocyte-related blood transcriptional modules (BTMs) and upregulation of T-cell related BTMs, as well as higher month 3 (vs baseline) (CSP)-specific CD4+ T-cell responses. For some RTS,S/AS01-associated BTMs, month 3 levels correlated with anti-circumsporozoite protein (CSP) IgM and inversely with anti-CSP IgG responses. There were few RTS,S/AS01-associated BTMs whose month 3 levels correlated with malaria risk. In contrast, baseline levels of dendritic cell and monocyte RTS,S/AS01-associated BTMs correlated with malaria risk. A cross-study analysis supported generalizability of these correlations to healthy, malaria-naïve adults, suggesting inflammatory monocytes may inhibit protective RTS,S/AS01-induced responses.
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| Overall design |
1,900 samples were sequenced in 5 batches of 384-well plates. Two positive (human universal reference) and two negative (water) controls were included in each plate. No replicates of samples were performed.
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| Contributor(s) |
Carnes J, Moncunill G, Young WC, Carpp LN, Rosa SD, Campo JJ, Nhabomba AJ, Mpina M, Jairoce C, Finak G, Haas P, Murie C, Van P, Sanz H, Dutta S, Mordmüller B, Agnandji ST, Díez-Padrisa N, Williams NA, Aponte JJ, Valim C, Neafsey DE, Daubenberger C, McElrath J, Dobaño C, Stuart K, Gottardo R |
| Citation(s) |
35060479 |
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| Submission date |
Jun 04, 2021 |
| Last update date |
Feb 02, 2022 |
| Contact name |
Carlota Dobaño |
| Organization name |
ISGlobal, Hospital Clínic - Universitat de Barcelona
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| Street address |
Rosselló 153
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| City |
Barcelona |
| ZIP/Postal code |
08036 |
| Country |
Spain |
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| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL29107 |
Illumina NextSeq 500 (blank sample) |
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| Samples (1925)
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| Relations |
| BioProject |
PRJNA735200 |
| SRA |
SRP322730 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE176156_concatenated_unique_refseq_umi_counts.tsv.gz |
19.1 Mb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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