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

Fahreta Hamzabegovic; Johannes B Goll; William F Hooper; Sharon Frey; Casey E Gelber; Getahun Abate

doi:10.1038/s41541-020-0156-y

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

NPJ Vaccines. 2020 Jan 23;5(1):6. doi: 10.1038/s41541-020-0156-y. eCollection 2020.

Authors

Fahreta Hamzabegovic^#¹, Johannes B Goll^#², William F Hooper², Sharon Frey¹, Casey E Gelber², Getahun Abate¹

Affiliations

¹ 1Division of Infectious Diseases, Allergy and Immunology, Saint Louis University, Saint Louis, MO USA.
² 2EMMES, Rockville, MD USA.

^# Contributed equally.

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.

Keywords: Adjuvants; Peptide vaccines.

Abstract

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