Investigating the impact of COVID-19 vaccines on the red blood cell immune function by omics-based approaches

The role of red blood cells (RBC) in the immune system is increasingly recognized. However, RBC-derived molecules with an immunomodulatory role in health and disease, as well as in vaccine immunogenicity are still poorly investigated. Taking as a model the emergent COVID-19 vaccines, we aimed to investigate whether vaccines induce proteome and/or metabolome changes in RBCs able to affect T-cell immune activity, as a mechanistic test for vaccine immunization regulated by RBCs. Our ultimate goal is to identify RBC immunomodulators as potential co-adjuvants in the formulation of next-generation vaccines with bolstered efficacy and duration. A biobank of blood samples collected longitudinally under ‘omics’ quality control from subjects (n=39) that underwent vaccination for COVID-19 between April and September 2021 was created. This biobank is associated with extensive clinical data, including demographic data, COVID-19 PCR diagnosis, hematological and vaccine effectivity data. Linear Mixed Models, were used to evaluate the association between biometrical characteristics, health related habits, vaccine technology and vaccine effectivity and hematological parameters, along the different time-points (t0-t4) under study, i.e, before and after (24-72h or 30 days) of the first and second dose of vaccine. Statistical analyses were performed using R software version 4.1.2. Results showed significant differences (p<0.05) before/after vaccination in a set of hematological variables (e.g., hemoglobin, lymphocytes and monocytes values), as well in terms of vaccine effectivity and vaccine technology (mRNA or adenovirus – based vaccines). Preliminary data from proteomics and metabolomics analysis of RBCs along the different time-points (t0-4) of immunization response will be also presented and discussed. The knowledge gained with this project can generate important evidence-based recommendations intended to optimize vaccine immunization, by recognizing the impact of blood cells such RBCs in the immune system regulation.