Abstract
Vaccination procedures within the cattle industry are important disease control tools to minimize economic and welfare burdens associated with respiratory pathogens. However, new vaccine, antigen and carrier technologies are required to combat emerging viral strains and enhance the efficacy of respiratory vaccines, particularly at the point of pathogen entry. New technologies, specifically metabolomic profiling, could be applied to identify metabolite immune-correlates representative of immune protection following vaccination aiding in the design and screening of vaccine candidates. This study for the first time demonstrates the ability of untargeted UPLC-MS metabolomic profiling to identify metabolite immune correlates characteristic of immune responses following mucosal vaccination in calves. Male Holstein Friesian calves were vaccinated with Pfizer Rispoval® PI3 + RSV intranasal vaccine and metabolomic profiling of post-vaccination plasma revealed 12 metabolites whose peak intensities differed significantly from controls. Plasma levels of glycocholic acid, N-[(3α,5β,12α)-3,12-Dihydroxy-7,24-dioxocholan-24-yl]glycine, uric acid and biliverdin were found to be significantly elevated in vaccinated animals following secondary vaccine administration, whereas hippuric acid significantly decreased. In contrast, significant upregulation of taurodeoxycholic acid and propionylcarnitine levels were confined to primary vaccine administration. Assessment of such metabolite markers may provide greater information on the immune pathways stimulated from vaccine formulations and benchmarking early metabolomic responses to highly immunogenic vaccine formulations could provide a means for rapidly assessing new vaccine formulations. Furthermore, the identification of metabolic systemic immune response markers which relate to specific cell signaling pathways of the immune system could allow for targeted vaccine design to stimulate key pathways which can be assessed at the metabolic level.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-014-0138-z) contains supplementary material, which is available to authorized users.
Highlights
The vaccination of farm animals against endemic, genetically evolving and emerging pathogens is important to ensure animal health, and to reduce the costs associated with disease losses, either clinical or subclinical
Upon Bovine Parainfluenza Type3 Virus (BPI3V) challenge at day 70, BPI3V IgG antibody titre was maintained at significantly higher (p < 0.05) levels at days 70 and 75 in vaccinated calves compared to non-vaccinated calves indicating an adaptive primed immune response to infection
Whilst this approach has resulted in the majority of vaccines available today, new vaccine development is increasingly costly and it is imperative that the least promising candidates are eliminated from investigation as early as possible
Summary
The vaccination of farm animals against endemic, genetically evolving and emerging pathogens is important to ensure animal health, and to reduce the costs associated with disease losses, either clinical or subclinical. Gray et al Veterinary Research (2015) 46:7 the expenditure associated with animal vaccine development is not fully disclosed, the estimated budget required to develop a single FDA approved vaccine for human studies is estimated in the region of $1-2 billion [2]. The majority of these costs are attributed to the high failure rate of vaccine candidates/formulations, with only 1 in every 10 000 vaccine formulations gaining approval by the FDA [3]. As the expenditure associated with candidate vaccine development escalates with clinical trial progression, rapid vaccine screening methods which can assess candidate vaccine effectiveness at early trial stages in vivo are required to minimize financial outlay and improve the speed of vaccine development pipelines
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