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Flagellin adjuvanted F1/V subunit plague vaccine induces T cell and functional antibody responses with unique gene signatures.

06/2020

Journal Article

Authors:
Hamzabegovic, F.; Goll, J.B.; Hooper, W.F.; Frey, S.; Gelber, C.E.; Abate, G.

Secondary:
NPJ Vaccines

Volume:
5

Pagination:
6

Issue:
1

PMID:
31993217

URL:
https://pubmed.ncbi.nlm.nih.gov/31993217/;https://www.nature.com/articles/s41541-020-0156-y;https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978331/

DOI:
10.1038/s41541-020-0156-y

Keywords:
Adjuvants; Peptide vaccines.; CRID

Abstract:
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 for protective markers. 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 days 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 these responses were identified that could serve as potential correlates of protection.

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