530. Characterization of the Proteomic Changes via SARS-CoV-2 Infection or Vaccination in the COVID-19 Community Research Partnership (CCRP)

Abstract Background There remain important gaps in knowledge concerning the effects of SARS-CoV-2 infection or vaccination on the human blood proteome. Methods The CCRP is a longitudinal surveillance study with information on SARS-CoV-2 infections, vaccinations and associated humoral immune responses in over 37,000 individuals. We selected a sample of blood spots cards (n=510) from serum antibody studies obtained between October 2020 and April 2021 for mass spectrometry proteomics analysis covering 540 unique plasma proteins. We analyzed the quantified protein differences based on dried blood samples obtained before and after infection or vaccination among previously non-infected individuals (immune naïve) after adjustment for batch effects, age, sex, or prior diagnosis of cancer, cardiovascular or autoimmune disease, or diabetes. The majority of infected individuals were minimally symptomatic. Differentially expressed proteins were considered significant with an FDR adjusted p-value of < 0.05 and log2 fold change (L2FC) >0.2. Results We found 11 and 12 proteins differentially expressed proteins in the naïve/infected and naïve/vaccinated people respectively, of which 10 were shared. Hepatocyte growth factor receptor (HGF) was upregulated (L2FC 0.24; p < 0.001) only in those who were infected while fibrillarin (L2FC -0.24; p< 0.001) and lambda-crystallin homolog (L2FC -0.29, p < 0.001) were downregulated only in the vaccinated samples (Fig 1). The remaining DE protein were associated with a wide array of functions including metabolic, cytostructural, extracellular matrix and DNA regulatory processes. Conclusion We found changes in the proteome both from infection and vaccination. HGF, elevated in the infected, has been associated with endothelial inflammation, upregulation of pro-inflammatory cytokines to reduce lung fibrosis and is known to promote tissue repair. Fibrillarin, downregulated in the vaccinated, has been associated with higher rates of bacterial and viral clearance, inflammation reduction, and increased cell survival. These findings suggest detectable complex inflammation from mild to moderate infections. Further investigation is required to understand the mechanism of action and clinical implication of these findings. Disclosures All Authors: No reported disclosures.