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| Status |
Public on Nov 08, 2023 |
| Title |
Distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults [scRNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Pneumococcal infections cause serious illness and death among older adults. A capsular polysaccharide vaccine PPSV23 (Pneumovax®) and a conjugated polysaccharide vaccine PCV13 (Prevnar®) are used to prevent these infections, yet underlying immunological responses, and baseline predictors remain unknown. We recruited and vaccinated 39 older adults (>60 years) with PPSV23 or PCV13. Both vaccines induced strong antibody responses at day 28 and similar plasmablast transcriptional signatures at day 10, however, their baseline predictors were distinct. Analyses of baseline flow cytometry and RNA-seq data (bulk and single cell) revealed a novel baseline phenotype that is specifically associated with weaker PCV13 responses, characterized by i) increased expression of cytotoxicity-associated genes and increased CD16+ NK frequency; ii) increased Th17 and decreased Th1 cell frequency. Men were more likely to display this cytotoxic phenotype and mounted weaker responses to PCV13 than women. Baseline expression levels of a distinct gene set was predictive of PPSV23 responses. This first precision vaccinology study for pneumococcal vaccine responses of older adults uncovered novel and distinct baseline predictors that might transform vaccination strategies and initiate novel interventions.
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| Overall design |
Our study involved the single-cell RNA sequencing (scRNA-seq) profiling of peripheral blood mononuclear cells (PBMCs) obtained from 11 donors before PCV13 vaccination. Among these donors, six are strong responders (SR) to PCV13, and five are weak responders (WR).
***Submitter declares that the raw data will be available through dbGAP (phs002361) due to patient privacy concerns***
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| Web link |
https://www.nature.com/articles/s41590-023-01717-5
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| Contributor(s) |
Ucar D, Ravichandran S |
| Citation(s) |
38182669 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AG052608 |
Genomics and Epigenomics of the Elderly Response to Pneumococcal Vaccines |
THE JACKSON LABORATORY |
Jacques F Banchereau |
| P30 AG067988 |
Claude D. Pepper Older Americans Independence Center (P30 Clinical Trial Optional) |
UNIVERSITY OF CONNECTICUT HEALTH CENTER |
George A Kuchel |
| U01 AI165452 |
A deep longitudinal analysis of next generation influenza vaccines in older adults |
THE JACKSON LABORATORY |
George A Kuchel |
| R01 AI142086 |
High-resolution single cell profiling of vaccine responsiveness in the elderly |
THE JACKSON LABORATORY |
Duygu Ucar |
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| Submission date |
Nov 08, 2023 |
| Last update date |
Jan 08, 2024 |
| Contact name |
Duygu Ucar |
| E-mail(s) |
duygu.ucar@jax.org
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| Organization name |
The Jackson laboratory for Genomic Medicine
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| Street address |
10 Discovery Dr
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| City |
Farmington |
| State/province |
CT |
| ZIP/Postal code |
06032 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (11)
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| GSM7886593 |
PBMC, Baseline, Strong Responder (SR), PREV10 |
| GSM7886594 |
PBMC, Baseline, Strong Responder (SR), PREV18 |
| GSM7886595 |
PBMC, Baseline, Weak Responder (WR), PREV23 |
| GSM7886596 |
PBMC, Baseline, Weak Responder (WR), PREV31 |
| GSM7886597 |
PBMC, Baseline, Strong Responder (SR), PREV36 |
| GSM7886598 |
PBMC, Baseline, Weak Responder (WR), PREV45 |
| GSM7886599 |
PBMC, Baseline, Weak Responder (WR), PREV66 |
| GSM7886600 |
PBMC, Baseline, Strong Responder (SR), PREV71 |
| GSM7886601 |
PBMC, Baseline, Strong Responder (SR), PREV72 |
| GSM7886602 |
PBMC, Baseline, Weak Responder (WR), PREV89 |
| GSM7886603 |
PBMC, Baseline, Strong Responder (SR), PREV99 |
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| Relations |
| BioProject |
PRJNA1037044 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE247277_RAW.tar |
388.9 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
| Raw data not provided for this record |
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