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

Sean Lipsit; Antonio Facciuolo; Erin Scruten; James Wilkinson; Graham Plastow; Anthony Kusalik; Scott Napper

doi:10.1016/j.jvacx.2022.100167

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

Vaccine X. 2022 May 9:11:100167. doi: 10.1016/j.jvacx.2022.100167. eCollection 2022 Aug.

Authors

Sean Lipsit^{1

2}, Antonio Facciuolo¹, Erin Scruten¹, James Wilkinson³, Graham Plastow³, Anthony Kusalik⁴, Scott Napper^{1

2}

Affiliations

¹ Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada.
² Department of Biochemistry, Microbiology, and Immunology, University of Saskatchewan, Saskatoon, SK, Canada.
³ Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
⁴ Department of Computer Science, University of Saskatchewan, Saskatoon, SK, Canada.

Abstract

Individual variability in responses to vaccination can result in vaccinated subjects failing to develop a protective immune response. Vaccine non-responders can remain susceptible to infection and may compromise efforts to achieve herd immunity. Biomarkers of vaccine unresponsiveness could aid vaccine research and development as well as strategically improve vaccine administration programs. We previously vaccinated piglets (n = 117) against a commercial Mycoplasma hyopneumoniae vaccine (RespiSure-One) and observed in low vaccine responder piglets, as defined by serum IgG antibody titers, differential phosphorylation of peptides involved in pro-inflammatory cytokine signaling within peripheral blood mononuclear cells (PBMCs) prior to vaccination, elevated plasma interferon-gamma concentrations, and lower birth weight compared to high vaccine responder piglets. In the current study, we use kinome analysis to investigate signaling events within PBMCs collected from the same high and low vaccine responders at 2 and 6 days post-vaccination. Furthermore, we evaluate the use of inflammatory plasma cytokines, birthweight, and signaling events as biomarkers of vaccine unresponsiveness in a validation cohort of high and low vaccine responders. Differential phosphorylation events (FDR < 0.05) within PBMCs are established between high and low responders at the time of vaccination and at six days post-vaccination. A subset of these phosphorylation events were determined to be consistently differentially phosphorylated (p < 0.05) in the validation cohort of high and low vaccine responders. In contrast, there were no differences in birth weight (p > 0.5) and plasma IFNγ concentrations at the time of vaccination (p > 0.6) between high and low responders within the validation cohort. The results in this study suggest, at least within this study population, phosphorylation biomarkers are more robust predictors of vaccine responsiveness than other physiological markers.

Keywords: Biomarker; Kinome; Phosphorylation; Vaccine Response.