Longitudinal Plasma Proteome of Pfizer/BNT162b2 Pre- and Postbooster Vaccinated Healthy Individuals Reveals Distinct Protein Profiles upon SARS-CoV-2 Spike Protein Stimulation

A COVID-19 booster dose has been found to be effective in our fight against SARS-CoV-2 infection. However, their long-term beneficial or adverse effects among healthy individuals are not fully understood. We investigated the impact of the Pfizer-BioNTech-(BNT162b2) booster dose on plasma proteome profiles of fully vaccinated healthy individuals in a mimic of reinfection to understand the disease mechanisms and to identify novel diagnostic and prognostic biomarkers. In contrast to prebooster, postbooster recipients exhibited a distinct proteomic signature following SARS-CoV-2 spike (S) protein stimulation. The gene ontology (GO) terms of biological processes revealed the five most significant functions enriched in stress and immune responses, especially via complement and blood coagulation systems. Likewise, the Reactome pathway demonstrated significant activation of complement cascade, platelet degranulation, and innate immune systems. Moreover, the protein–protein interaction network exhibited regulation of body fluid levels and acute inflammatory response. In summary, our study identified abundant dysregulated signatures predominantly associated with the complement, the innate immune system, and platelet degranulation. Besides eliciting humoral immunity, our study also found key proteins involved in blood coagulation pathways that could perhaps shed light on individuals exhibiting comorbidities associated with COVID-19 vaccination. Therefore, factors dysregulated following SARS-CoV-2 spike (S) protein stimulation may provide insights into pathways potentially implicated in post-vaccination reactions.