Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in young children. Although the disease may be severe in immunocompromised, young and elderly people, there is… Click to show full abstract
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in young children. Although the disease may be severe in immunocompromised, young and elderly people, there is currently no approved vaccine. We previously reported the development and immunological assessment of a novel intranasal vaccine formulation consisting of a truncated version of the RSV fusion protein (∆F) combined with a three-component adjuvant (TriAdj). Now, we aim to investigate the mechanism of action of the ∆F/TriAdj formulation by searching for metabolic alterations caused by intranasal immunization and RSV challenge. We carried out untargeted lipidomics and sub-metabolome profiling (carboxylic acids and amine/phenol-containing metabolites) of lung tissue from ∆F/TriAdj-immunized and non-immunized, RSV-challenged mice. We observed significant changes of lipids involved in the lung surfactant layer for the non-immunized animals compared to healthy controls, but not for the immunized mice. Metabolic pathways involving synthesis and regulation of amino acids and unsaturated fatty acids were also modulated by immunization and RSV challenge. This study illustrates that lipidomic and metabolomic profiling could provide a more comprehensive understanding of the immunological and metabolic alterations caused by RSV and the modulation effected by the ∆F/TriAdj formulation.
               
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