April 23, 2024  |  Preprint

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

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This study combines a nanoparticle-based proteomic workflow with tandem mass tag labeling to analyze proteomic changes in response to the Pfizer-BioNTech mRNA COVID-19 vaccine. It identifies significant protein variations in individuals, providing insights into the molecular mechanisms driving diverse immune responses to vaccination.

Abstract

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 nanoparticle-based workflow to quantify over 3,000 proteins from 48 human plasma samples, providing the deepest view into COVID-19 vaccine-related plasma proteome study. We identified 69 proteins exhibiting a boosted response to the vaccine after the second dose. Additionally, 74 proteins were differentially regulated between seven volunteers, who contracted COVID-19 despite receiving two doses of the vaccine, and the ones who did not contract COVID-19. These findings offer valuable insights into individual variability in response to vaccination, demonstrating the potential of personalized medicine approaches in vaccine development.

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DOI: 10.1101/2024.04.22.589104

  • Tags
  • Infectious Disease
  • Biomarker Discovery
  • Serum or Plasma
  • Human