Journal of proteome researchFeb 3, 2026

Changes in Blood Proteins Before and After Pfizer/BNT162b2 Booster Vaccination Show Different Responses to Coronavirus Spike Protein

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Feb 4, 2026

Abstract

Post-booster recipients showed a distinct proteomic signature following SARS-CoV-2 spike protein stimulation.

The plasma proteome profiles of fully vaccinated healthy individuals changed after receiving the Pfizer-BioNTech booster dose.
Significant functions related to stress and immune responses were identified, particularly involving the complement and blood coagulation systems.
Activation of the complement cascade, platelet degranulation, and innate immune systems was observed following stimulation.
Dysregulated protein signatures were predominantly linked to the complement system, innate immune response, and blood coagulation pathways.
Key proteins associated with blood coagulation may provide insights into comorbidities related to COVID-19 vaccination.
Findings suggest that factors altered after spike protein stimulation could inform on potential post-vaccination reactions.

Simplified

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.