Plasma Metabolomic Alterations Induced by COVID-19 Vaccination Reveal Putative Biomarkers Reflecting the Immune Response

Abstract

Vaccination is currently the most effective strategy for the mitigation of the COVID-19 pandemic. mRNA vaccines trigger the immune system to produce neutralizing antibodies (NAbs) against SARS-CoV-2 spike proteins. However, the underlying molecular processes affecting immune response after vaccination remain poorly understood, while there is significant heterogeneity in the immune response among individuals. Metabolomics have often been used to provide a deeper understanding of immune cell responses, but in the context of COVID-19 vaccination such data are scarce. Mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR)-based metabolomics were used to provide insights based on the baseline metabolic profile and metabolic alterations induced after mRNA vaccination in paired blood plasma samples collected and analysed before the first and second vaccination and at 3 months post first dose. Based on the level of NAbs just before the second dose, two groups, “low” and “high” responders, were defined. Distinct plasma metabolic profiles were observed in relation to the level of immune response, highlighting the role of amino acid metabolism and the lipid profile as predictive markers of response to vaccination. Furthermore, levels of plasma ceramides along with certain amino acids could emerge as predictive biomarkers of response and severity of inflammation.

NMR Metabolomics Methods for Investigating Disease

“…114 Another longitudinal study evaluated the effect of a different mRNA vaccine, BNT162b2. 117 Metabolite profiles associated with antibody levels induced by the vaccine were analyzed in blood plasma by combining NMR and mass spectrometry. 117 This study highlighted the role of amino acid metabolism and lipids as predictive markers of response to vaccination.…”

“…These results are in accordance with an independent observation that serum antibody levels in individuals with a history of COVID-19 reach a plateau after the first dose . Another longitudinal study evaluated the effect of a different mRNA vaccine, BNT162b2 . Metabolite profiles associated with antibody levels induced by the vaccine were analyzed in blood plasma by combining NMR and mass spectrometry .…”

Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19

“…An impressive scientific and economic effort allowed the early appearance of prophylactic measures for SAR-CoV-2 infection and several studies have investigated the putative metabolic alterations induced by mRNA vaccines. Using a combination of LC-MS and NMR spectroscopy, Dagla et al (2022) analyzed plasma samples from patients up to 3 months after the first dose and observed distinct plasma metabotypes in relation to the level of immune response, highlighting the role of amino acid metabolism and the lipid profile as predictive markers of response to vaccination ( Dagla et al, 2022 ). Equivalent variations in the lipoproteins (but not in the metabolome) were observed by serum NMR profiling of vaccinated individuals ( Ghini et al, 2022a ).…”

Crosstalk between COVID-19 Infection and Kidney Diseases: A Review on the Metabolomic Approaches

“…Alterations in metabolomics in the plasma were detected in different studies. In one such study, alterations in plasma were analyzed, and changes in different amino acids and lipid profiles were detected as a response to vaccination against COVID-19 [ 175 ]. COVID-19 patients’ lipid and metabolite changes correlate with their disease progression, suggesting that COVID-19 impacted their entire body metabolism.…”