Deep, Unbiased,and Quantitative Mass Spectrometry-BasedPlasma Proteome Analysis of Individual Responses to mRNA COVID-19Vaccine

Global campaign against COVID-19 have vaccinated a significant portion of the world population in recent years. Combating the COVID-19 pandemic with mRNA vaccines played a pivotal role in the global immunization effort. However, individual responses to a vaccine are diverse and lead to varying vaccination efficacy. Despite significant progress, a complete understanding of the molecular mechanisms driving the individual immune response to the COVID-19 vaccine remains elusive. To address this gap, we combined a novel nanoparticle-based proteomic workflow with tandem mass tag (TMT) labeling, to quantitatively assess the proteomic changes in a cohort of 12 volunteers following two doses of the Pfizer-BioNTech mRNA COVID-19 vaccine. This optimized protocol seamlessly integrates comprehensive proteome analysis with enhanced throughput by leveraging the enrichment of low-abundant plasma proteins by engineered nanoparticles. Our data demonstrate the ability of this workflow to quantify over 3,000 proteins, providing the deepest view into COVID-19 vaccine-related plasma proteome study. We identified 69 proteins with boosted responses post-second dose and 74 proteins differentially regulated between individuals who contracted COVID-19 despite vaccination and those who did not. These findings offer valuable insights into individual variability in response to vaccination, demonstrating the potential of personalized medicine approaches in vaccine development.