Comprehensive Lipidomic and Metabolomic Analysis for Studying Metabolic Changes in Lung Tissue Induced by a Vaccine against Respiratory Syncytial Virus

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 (ΔF)
combined with a three-component adjuvant (TriAdj). Now, we aim to
investigate the mechanism of action of the ΔF/TriAdj formulation
by searching for metabolic alterations caused by intranasal immunization
and the RSV challenge. We carried out untargeted lipidomics and submetabolome
profiling (carboxylic acids and amine/phenol-containing metabolites)
of lung tissue from ΔF/TriAdj-immunized and nonimmunized, RSV-challenged
mice. We observed significant changes of lipids involved in the lung
surfactant layer for the nonimmunized animals compared to healthy
controls but not for the immunized mice. Metabolic pathways involving
the synthesis and regulation of amino acids and unsaturated fatty
acids were also modulated by immunization and the 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 ΔF/TriAdj
formulation.