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| Status |
Public on Dec 31, 2019 |
| Title |
Flagellin adjuvanted F1/V subunit plague vaccine induces T cell and functional antibody responses with unique gene signatures |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Yersinia pestis, the cause of plague, could be weaponized. Unfortunately, development of new vaccines is limited by lack of correlates of protection. We used pre- and post-vaccination sera and peripheral blood mononuclear cells from a flagellin adjuvanted F1/V vaccine trial to evaluate potential gene expression markers that correlated with macrophage protection. Here, we report for the first time in humans that inverse caspase 3 levels which are measures of protective antibody significantly increased by 29% and 75% on day 14 and 28 post-second vaccination, respectively. In addition, there were significant increases in T cell responses on day 28 post-second vaccination. The strongest positive and negative correlations between protective antibody levels and gene expression signatures were identified for IFNG and ENSG00000225107 genes, respectively. Flagellin/F1/V subunit vaccine induced macrophage-protective antibody and significant CD4+ T cell responses. Several genes associated with macrophage-protective antibody were identified that could serve as potential correlates of protection.
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| Overall design |
Stored samples from a recently completed clinical trial (DMID 08-0066) were used. DMID 08-0066 was a phase I, randomized, double blind, placebo controlled, dose-escalation trial to evaluate flagellin/F1/V, a plague vaccine, in healthy adults. In the DMID 08-0066 clinical trial, volunteers were vaccinated with two doses of 1, 3, 6 or 10 µg flagellin-adjuvanted F1/V subunit plague vaccine 28 days apart. Sera and peripheral blood mononuclear cells (PBMC) collected at three time points (pre-vaccination, and days 14 and 28 post-second dose) from volunteers vaccinated with 6 μg and 10 μg of flagellin adjuvanted F1/V vaccine were used in this study. These two post vaccination time points from the high dose groups were selected because of higher antibody responses. Clinical samples from these two timepoints, sera stored at -80C and PBMC stored in liquid nitrogen, were used in this study. Supplementary Figure 1 summarizes the number of subjects by treatment group and assay type used in this study. As part of this study, DMID 15-0104, additional blood samples were collected from 7 volunteers who received 6 μg or 10 μg Flagellin/F1/V vaccine in the 08-0066 trial. Sera and PBMC from these additional blood samples were used to optimize immunological assays for this study. For transcriptomics, PBMCs were stimulated with F1/V vaccine antigen for 24 hours before RNA was extracted.
***The submitter declares that the raw data cannot be made available via any mechanism due to patient privacy concerns.***
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| Contributor(s) |
Hamzabegovic F, Goll JB, Hooper WF, Frey S, Gelber CE, Abate G |
| Citation(s) |
31993217 |
| Submission date |
Sep 04, 2019 |
| Last update date |
Feb 03, 2020 |
| Contact name |
Johannes Goll |
| Organization name |
The Emmes Company
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| Department |
Bioinformatics Service Group
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| Street address |
401 N Washington St
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| City |
Rockville |
| State/province |
MD |
| ZIP/Postal code |
20850 |
| Country |
USA |
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| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (41)
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| Relations |
| BioProject |
PRJNA563907 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE136878_abate_npj_2019_rnaseq_featurecounts.tab.gz |
1.9 Mb |
(ftp)(http) |
TAB |
| Raw data not provided for this record |
| Processed data are available on Series record |
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