Kinome profiling of peripheral blood mononuclear cells collected prior to vaccination reveals biomarkers and potential mechanisms of vaccine unresponsiveness in pigs

Abstract

Inter-individual variance in host immune responses following vaccination can result in failure to develop protective immunity leaving individuals at risk for infection in addition to compromising herd immunity. While developing more efficacious vaccines is one strategy to mitigate this problem, predicting vaccine responsiveness prior to vaccination could inform which individuals require adjunct disease management strategies. To identify biomarkers of vaccine responsiveness, a cohort of pigs (n = 120) were vaccinated and pigs representing the high (n = 6; 90th percentile) and low (n = 6; 10th percentile) responders based on vaccine-specific antibody responses following vaccination were further analyzed. Kinase-mediated phosphorylation events within peripheral blood mononuclear cells collected prior to vaccination identified 53 differentially phosphorylated peptides when comparing low responders with high responders. Functional enrichment analysis revealed pro-inflammatory cytokine signaling pathways as dysregulated, and this was further substantiated by detection of higher (p < 0.01) concentrations of interferon-gamma in plasma of low responders compared to high responders prior to vaccination. In addition, low responder pigs with high plasma interferon-gamma showed lower (p < 0.01) birth weights than high responder pigs. These associations between vaccine responsiveness, cytokine signaling within peripheral immune cells, and body weight in pigs provide both evidence and insight into potential biomarkers for identifying low responders to vaccination.

Influence of genetics and the pre-vaccination blood transcriptome on the variability of antibody levels after vaccination against Mycoplasma hyopneumoniae in pigs

“…Within-population variability has been shown for Ab response to vaccines against influenza [ 27 ] and porcine reproductive and respiratory syndrome [ 28 ] viruses, and tetanus bacteria [ 29 ], and to the bacterial antigens K88ab, K88ac, and O149 [ 30 ]. We and others have also reported individual variability of serum M. hyo -specific Ab induced after vaccination in various populations [ 31 , 32 ].…”

“…A previous study in pigs did not identify any biomarkers in the blood transcriptome before vaccination for the prediction of M. hyo Ab levels measured 10 days after a booster vaccination [ 42 ]. It should be noted that, in the same population, the kinome (global cellular kinase activity) revealed prior vaccination candidate biomarkers [ 32 ]. In our study, we investigated the early, maximum intensity, and persistence of Ab responses and searched for predictors of the intensity of vaccine response by studying genes that are expressed in pre-vaccination blood.…”

Molecular mechanisms governing circulating immune cell heterogeneity across different species revealed by single‐cell sequencing

“…As the supervisor and executor of body defense, PBMCs play important roles in mediating innate and adaptive immune responses, maintaining immune homeostasis, and reflecting the real‐time cellular and humoral immune state of the whole body. As such, PBMCs are widely used in the fields of immunology, 1,2 infectious diseases, 3,4 cancer, 5 vaccine development, 6 transplantation 7 and high‐throughput screening for therapeutic antibodies 8 . As a commonly used ex vivo cellular model in immunological function studies, PBMCs also play a vital role in immunological research and immunotherapy, and have been used to predict diagnostic biomarkers and discover potential immunotherapy targets 9,10 …”

Signaling differences in peripheral blood mononuclear cells of high and low vaccine responders prior to, and following, vaccination in piglets

“…These phosphorylation biomarkers discriminated the susceptibility of honeybee colonies to Varroa mite infestation prior to exposure to the pathogen, demonstrating proof-of-concept that phosphorylation biomarkers have value for phenotype prediction [46] , [47] . Previously, our group conducted transcriptional and kinome analysis on PBMCs collected from piglets prior to M. hyopneumoniae vaccination to identify differences between high and low vaccine responders [28] , [35] . While the transcriptional analysis did not detect pre-vaccination differences in gene expression, kinome analysis revealed differential phosphorylation events in PBMCs prior to vaccination that were functionally enriched in pro-inflammatory cytokine signaling [28] .…”