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Post-booster longitudinal plasma proteomic changes following BNT162b2 COVID-19 vaccination in Qatar

*Corresponding author for this work
  • Hamad bin Khalifa University
  • Hamad Medical Corporation
  • Qatar University

Research output: Contribution to journalArticlepeer-review

Abstract

Background – The COVID-19 pandemic imposed a major global health and economic burden. Although the pandemic was no longer declared a public health emergency of international concern in May 2023, SARS-CoV-2 variants continue to emerge, and millions remain affected by long COVID. This raises the question whether continued vaccination provides lasting benefits in preventing viral transmission and severe illness. Aim – This longitudinal study assessed the effects of the third BNT162b2 mRNA vaccine dose on the circulating proteome for 6 months. Methods – Plasma levels of 354 unique proteins were quantified before, and at 3- and 6-months post-booster using Olink technology in 70 healthy individuals; 35 infection-naïve and 35 previously infected individuals (18 infected before, 17 after completing the two-dose regimen). Results – Infection-naïve individuals showed altered levels of eleven and eight proteins at 3- and 6-months post-booster, respectively, including a significant sustained increase in PARP-1 (FC = 1.53, p=8.59x10-5, pFDR=0.01) and significant decrease in MMP-7 (FC = 0.68, p=4.58x10-5, pFDR=0.01), in addition to elevated levels of MMP-1 (FC = 1.46, p=0.04, pFDR>0.05) and decrease in 4E-BP1 (FC = 0.58, p=0.01, pFDR>0.05) at 6 months post-booster. Similarly, previously infected individuals, in particular those with earlier infections before receiving the second dose exhibited a significant sustained upregulation of PARP-1 (FC = 2.10, p=1.19x10-5, pFDR=0.003) and downregulation of MMP-7 (FC = 0.58, p=2.19x10-5, pFDR=0.003) at 6-months post-booster. Notably, PARP-1 and MMP-7 were consistently affected across all individuals. Longitudinal proteome profiling revealed dysregulation of key inflammatory proteins for up to 6 months post-booster, including PARP-1 and MMP-7 (pFDR=1.58x10–8 and pFDR=1.59x10-5, respectively). Conclusions – These findings provide insights into the temporal dynamics of circulating proteomic responses following booster vaccination, highlighting molecular features that may be relevant to immune readiness and post-vaccination inflammatory processes.

Original languageEnglish
Article number1762522
JournalFrontiers in Immunology
Volume17
Early online dateApr 2026
DOIs
Publication statusPublished - Apr 2026

Keywords

  • BNT162b2
  • MMP-7
  • PARP-1
  • SARS-CoV-2
  • booster
  • proteomic profiling

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