Alterations in the Human Plasma Lipidome in Response to Tularemia Vaccination

• Type of Material: Article
• Authors: Kristal M. Maner-Smith, Emory University; Johannes B. Goll, Emmes Co; Manoj Khadka, Emory University; Travis L. Jensen, Emmes Co; Jennifer K. Colucci, Emory University; Casey E. Gelber, Emmes Co; Carolyn J. Albert, St. Louis University; Steven Bosinger, Emory University; Jacob D. Franke, St. Louis University; Muktha Natrajan, Emory University; Nadine Rouphael, Emory University; Robert A. Johnson, US Department of Health and Human Services; Patrick Sanz, National Institute of Allergy and Infectious Diseases; Evan Anderson, Emory University; Daniel F. Hoft, St. Louis University; Mark Mulligan, Emory University; David A. Ford, St. Louis University; Eric Ortlund, Emory University
• Language: English
• Date: 2020-09-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/vaccines8030414
• Title of Journal or Parent Work: VACCINES
• Volume: 8
• Issue: 3
• Start Page: 1
• End Page: 14
• Grant/Funding Information: This work was supported by awards from the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases at the National Institutes of Health to the Emory Vaccine and Treatment Evaluation Unit, contracts HHSN272200800005C and HHSN272201300018I, St. Louis University contract HHSN2722013000021I, and EMMES contract HHSN272201500002C. We also acknowledge the support of the Georgia Research Alliance to The Hope Clinic. This study was supported in part by the Emory Integrated Lipidomics Core (EILC), which is subsidized by the Emory University School of Medicine and is one of the Emory Integrated Core Facilities. Additional support was provided by the Georgia Clinical & Translational Science Alliance of the National Institutes of Health under Award Number UL1TR002378.
• Keywords: CHOLESTEROL-SYNTHESIS; inflammation; CERAMIDE; Immunology; SYSTEMS; Life Sciences & Biomedicine; 5-hydroxyeicosatetraenoic (5HETE); Medicine, Research & Experimental; lipidomics; ENDOCANNABINOIDS; MASS-SPECTROMETRY; tularemia; EXTRACTS; Science & Technology; MACROPHAGES; vaccine response; BIOLOGICAL SAMPLES; QUANTITATION; SHOTGUN LIPIDOMICS; oxylipins; Research & Experimental Medicine
• Research Categories: Health Sciences, Immunology; Health Sciences, Public Health; Biology, Virology

Abstract

Tularemia is a highly infectious and contagious disease caused by the bacterium Francisella tularensis. To better understand human response to a live-attenuated tularemia vaccine and the biological pathways altered post-vaccination, healthy adults were vaccinated, and plasma was collected pre-and post-vaccination for longitudinal lipidomics studies. Using tandem mass spectrometry, we fully characterized individual lipid species within predominant lipid classes to identify changes in the plasma lipidome during the vaccine response. Separately, we targeted oxylipins, a subset of lipid mediators involved in inflammatory pathways. We identified 14 differentially abundant lipid species from eight lipid classes. These included 5-hydroxyeicosatetraenoic acid (5-HETE) which is indicative of lipoxygenase activity and, subsequently, inflammation. Results suggest that 5-HETE was metabolized to a dihydroxyeicosatrienoic acid (DHET) by day 7 post-vaccination, shedding light on the kinetics of the 5-HETE-mediated inflammatory response. In addition to 5-HETE and DHET, we observed pronounced changes in 34:1 phosphatidylinositol, anandamide, oleamide, ceramides, 16:1 cholesteryl ester, and other glycerophospholipids; several of these changes in abundance were correlated with serum cytokines and T cell activation. These data provide new insights into alterations in plasma lipidome post-tularemia vaccination, potentially identifying key mediators and pathways involved in vaccine response and efficacy.