Alterations in the human plasma lipidome in response to Tularemia vaccination

Abstract

Tularemia is a rare but highly contagious and potentially fatal disease caused by bacteria Francisella tularensis where as few as ten inhaled organisms can lead to an infection, making it one of the most infectious microorganisms known and a potential bioweapon. To better understand the response to a live, attenuated tularemia vaccine and the biological pathways altered post-vaccination, healthy adults were vaccinated by scarification and plasma was collected pre- and post-vaccination for longitudinal lipidomics studies. Using tandem mass spectrometry, we identified and quantified individual lipid molecular species within representative lipid classes in plasma to characterize alterations 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), an eicosanoid produced following arachidonic acid liberation and epoxygenation, 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 several 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.