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Metabolomic and Immunological Profiling of Respiratory Syncytial Virus Infection after Intranasal Immunization with a Subunit Vaccine Candidate

Author:
Sarkar, Indranil, Zardini Buzatto, Adriana, Garg, Ravendra, Li, Liang, van Drunen Littel-van den Hurk, Sylvia
Source:
Journal of proteome research 2019 v.18 no.3 pp. 1145-1161
ISSN:
1535-3907
Subject:
5-hydroxyindoleacetic acid, Respiratory syncytial virus, adjuvants, biosynthesis, carbon, congenital abnormalities, elderly, heart diseases, immunization, immunocompromised population, infants, inflammation, liquid chromatography, lungs, mechanism of action, metabolites, metabolomics, mice, morbidity, mortality, patients, phenol, proteome, serotonin, stable isotopes, subunit vaccines, tryptophan, urea cycle, xanthurenic acid
Abstract:
Respiratory syncytial virus (RSV) is a significant cause of mortality and morbidity in infants, the elderly, immunocompromised individuals, and patients with congenital heart diseases. Despite extensive efforts, a vaccine against RSV is still not available. We have previously reported the development of a subunit vaccine (ΔF/TriAdj) composed of a truncated version of the fusion protein (ΔF) and a polymer-based combination adjuvant (TriAdj). We compared inflammatory responses of ΔF/TriAdj-vaccinated and unvaccinated mice following intranasal challenge with RSV. Rapid and early inflammatory responses were observed in lung samples from both groups but modulated in the vaccinated group 7 days after the viral challenge. The underlying mechanism of action of ΔF/TriAdj was further studied through LC–MS-based metabolomic profiling by using ¹²C- or ¹³C-dansyl labeling for the amine/phenol submetabolome. RSV infection predominantly affected the amino acid biosynthesis pathways and urea cycle, whereas ΔF/TriAdj modulated the concentrations of almost all of the altered metabolites. Tryptophan metabolites were significantly affected, including indole, l-kynurenine, xanthurenic acid, serotonin, 5-hydroxyindoleacetic acid, and 6-hydroxymelatonin. The results from the present study provide further mechanistic insights into the mode of action of this RSV vaccine candidate and have important implications in the design of metabolic therapeutic interventions.
Agid:
6323369