Abstract
Bovine 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.
Highlights
Bovine Respiratory Disease (BRD) is a multifactorial disease characteristic of a viral-bacterial synergistic infection with predisposition from environmental stressors [1]
The viral pathogens associated with BRD [Bovine Parainfluenza Virus type-3 (BPI3V), Bovine Respiratory Syncytial Virus, Bovine Viral Diarrhoea Virus and Bovine Herpes Virus-1] impair immune responses in infected animals and damage the respiratory tract allowing the establishment of secondary infections, that may develop further into bacterial pneumonia [8]
Plasma CA levels were found to increase significantly only in vaccinated animals over day 0 to 20 p.i. (FC = 2.77) with no significant changes evident in non-vaccinated animal plasma. This is the first study to report the potential to differentiate between infected animals with differing vaccination status through the use of metabolomic profiling techniques (DIVA metabolomics)
Summary
Bovine Respiratory Disease (BRD) is a multifactorial disease characteristic of a viral-bacterial synergistic infection with predisposition from environmental stressors [1]. The viral pathogens associated with BRD [Bovine Parainfluenza Virus type-3 (BPI3V), Bovine Respiratory Syncytial Virus, Bovine Viral Diarrhoea Virus and Bovine Herpes Virus-1] impair immune responses in infected animals and damage the respiratory tract allowing the establishment of secondary infections, that may develop further into bacterial pneumonia [8]. Vaccinated animals can successfully clear viral infections faster than non-vaccinated animals through immune memory response, reducing the associated viral tissue damage or impairment of immune functions preventing the establishment of secondary bacterial and mycoplasma infections [6]. Halting viral disease progression to more severe and costly secondary bacterial infections through the identification of vaccine failure animals during infection outbreaks would reduce the level of antibiotic use in the agricultural industry
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