Serum Proteome Signatures of Anti-SARS-CoV-2 Vaccinated Healthcare Workers in Greece Associated with Their Prior Infection Status †

Over the course of the pandemic, proteomics, being in the frontline of anti-COVID-19 research, has massively contributed to the investigation of molecular pathogenic properties of the virus. However, data on the proteome on anti-SARS-CoV-2 vaccinated individuals remain scarce. This study aimed to identify the serum proteome characteristics of anti-SARS-CoV-2 vaccinated individuals who had previously contracted the virus and comparatively assess them against those of virus-naïve vaccine recipients. Blood samples of n = 252 individuals, out of whom n = 35 had been previously infected, were collected in the “G. Gennimatas” General Hospital of Thessaloniki, from 4 January 2021 to 31 August 2021. All participants received the BNT162b2 mRNA COVID-19 vaccine (Pfizer/BioNTech). A label-free quantitative proteomics LC-MS/MS approach was undertaken, and the identified proteins were analyzed using the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes) databases as well as processed by bioinformatics tools. Titers of total RBD-specific IgGs against SARS-CoV-2 were also determined using the SARS-CoV-2 IgG II Quant assay. A total of 47 proteins were significantly differentially expressed, the majority of which were down-regulated in sera of previously infected patients compared to virus-naïve controls. Several pathways were affected supporting the crucial role of the humoral immune response in the protection against SARS-CoV-2 infection provided by COVID-19 vaccination. Overall, our comprehensive proteome profiling analysis contributes novel knowledge of the mechanisms of immune response induced by anti-SARS-CoV-2 vaccination and identified protein signatures reflecting the immune status of vaccine recipients.