DIVA metabolomics: Differentiating vaccination status following viral challenge using metabolomic profiles

dc.contributor.authorGray, Darren W.
dc.contributor.authorWelsh, Michael D.
dc.contributor.authorMansoor, Fawad
dc.contributor.authorDoherty, Simon
dc.contributor.authorChevallier, Olivier P.
dc.contributor.authorElliott, Christopher T.
dc.contributor.authorMooney, Mark H.
dc.descriptionPublication history: Accepted - 5 March 2018; Published online - 4 April 2018en_US
dc.description.abstractBovine Respiratory Disease (BRD) is a major source of economic loss within the agricultural industry. Vaccination against BRD-associated viruses does not offer complete immune protection and vaccine failure animals present potential routes for disease spread. Serological differentiation of infected from vaccinated animals (DIVA) is possible using antigen-deleted vaccines, but during virus outbreaks DIVA responses are masked by wild-type virus preventing accurate serodiagnosis. Previous work by the authors has established the potential for metabolomic profiling to reveal metabolites associated with systemic immune responses to vaccination. The current study builds on this work by demonstrating for the first time the potential to use plasma metabolite profiling to differentiate between vaccinated and non-vaccinated animals following infection-challenge. Male Holstein Friesian calves were intranasally vaccinated (Pfizer RISPOVAL®PI3+RSV) and subsequently challenged with Bovine Parainfluenza Virus type-3 (BPI3V) via nasal inoculation. Metabolomic plasma profiling revealed that viral challenge led to a shift in acquired plasma metabolite profiles from day 2 to 20 p.i., with 26 metabolites identified whose peak intensities were significantly different following viral challenge depending on vaccination status. Elevated levels of biliverdin and bilirubin and decreased 3-indolepropionic acid in non-vaccinated animals at day 6 p.i. may be associated with increased oxidative stress and reactive oxygen scavenging at periods of peak virus titre. During latter stages of infection, increased levels of N-[(3α,5β,12α)-3,12-dihydroxy-7,24-dioxocholan-24-yl]glycine and lysophosphatidycholine and decreased enterolactone in non-vaccinated animals may reflect suppression of innate immune response mechanisms and progression to adaptive immune responses. Levels of hexahydrohippurate were also shown to be significantly elevated in non-vaccinated animals from days 6 to 20 p.i. These findings demonstrate the potential of metabolomic profiling to identify plasma markers that can be employed in disease diagnostic applications to both differentially identify infected non-vaccinated animals during disease outbreaks and provide greater information on the health status of infected animals.en_US
dc.description.sponsorshipThis research was funded by a Department of Agriculture and Rural Development (DARD) Northern Ireland postgraduate studentship awarded to Darren Grayen_US
dc.identifier.citationGray, D. W., Welsh, M. D., Mansoor, F., Doherty, S., Chevallier, O. P., Elliott, C. T. and Mooney, M. H. (2018) ‘DIVA metabolomics: Differentiating vaccination status following viral challenge using metabolomic profiles’, PLOS ONE. Edited by A. C. Moore, 13(4), p. e0194488. doi: 10.1371/journal.pone.0194488.en_US
dc.publisherPublic Library of Scienceen_US
dc.rights© 2018 Gray et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.titleDIVA metabolomics: Differentiating vaccination status following viral challenge using metabolomic profilesen_US
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