Alterations in the Human Plasma Lipidome in Response to Tularemia Vaccination
Kristal M. Maner-Smith,
Johannes B. Goll,
Manoj Khadka,
Travis L. Jensen,
Jennifer K. Colucci,
Casey E. Gelber,
Carolyn J. Albert,
Steven E. Bosinger,
Jacob D. Franke,
Muktha Natrajan,
Nadine Rouphael,
Robert A. Johnson,
Patrick Sanz,
Evan J. Anderson,
Daniel F. Hoft,
Mark J. Mulligan,
David A. Ford,
Eric A. Ortlund
Affiliations
Kristal M. Maner-Smith
Department of Biochemistry, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA
Johannes B. Goll
The Emmes Company, Rockville, MD 20850, USA
Manoj Khadka
Department of Biochemistry, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA
Travis L. Jensen
The Emmes Company, Rockville, MD 20850, USA
Jennifer K. Colucci
Department of Biochemistry, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA
Casey E. Gelber
The Emmes Company, Rockville, MD 20850, USA
Carolyn J. Albert
Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis,
MO 63104, USA
Steven E. Bosinger
Division of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA
Jacob D. Franke
Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis,
MO 63104, USA
Muktha Natrajan
Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
Nadine Rouphael
Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
Robert A. Johnson
Biomedical Advanced Research and Development Authority, US Department of Health and Human Services,
Washington, DC 20201, USA
Patrick Sanz
Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Rockville, MD 20892, USA
Evan J. Anderson
Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
Daniel F. Hoft
Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO 63104, USA
Mark J. Mulligan
Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
David A. Ford
Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis,
MO 63104, USA
Eric A. Ortlund
Department of Biochemistry, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA
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.
