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

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, pFDR0.05) and decrease in 4E-BP1 (FC = 0.58, p=0.01, pFDR0.05) 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.