25-Hydroxyvitamin D concentrations do not affect the humoral or cellular immune response following SARS-CoV-2 mRNA vaccinations

Background: To improve effectiveness of vaccination against SARS-CoV-2, it is important to identify factors that influence the immune response induced by vaccination. Evidence for the role of vitamin D in immune response against SARS-CoV-2 is contradictory. It is therefore of interest whether 25-hydroxyvitamin D (25[OH]D) concentrations affect the humoral and/or cellular response following SARS-CoV-2 vaccination. Methods: In this prospective cohort study, blood samples were collected from 98 SARS-CoV-2 naive health care workers (HCW) receiving the first two doses of either BNT162b2 or mRNA-1273 in 2021. Wild -type spike (S) protein binding and neutralizing antibodies were determined approximately three weeks after the first dose and four to five weeks after the second dose. Antigen specific T -cells and functionality (proliferative response and interferon gamma [IFN- gamma ] release) were determined in 18 participants four weeks after the second dose of BNT162b2. We studied the association between 25(OH)D concentrations, which were determined prior to vaccination, and humoral and cellular immune responses following vaccination. Results: We found no association between 25(OH)D concentrations (median 55.9 nmol/L [IQR 40.5 - 69.8]) and binding or neutralizing antibody titers after complete vaccination (fold change of antibody titers per 10 nmol/L 25(OH)D increase: 0.98 [95% CI 0.93 - 1.04] and 1.03 [95% CI: 0.96 - 1.11], respectively), adjusted for age, sex and type of mRNA vaccine. Subsequently, continuous 25(OH)D concentrations were divided into commonly used clinical categories ( <25 nmol/L [n = 6, 6%], 25 - 49 nmol/L [n = 33, 34%], 50 - 75 nmol/L [n = 37, 38%] and >= 75 nmol/L [n = 22, 22%]), but no association with the humoral immune response following vaccination was found. Also, 25(OH)D concentrations were not associated with the SARS-CoV-2 specific T cell response. Conclusion: No association was found between 25(OH)D concentrations and the humoral or cellular immune response following mRNA vaccination against SARS-CoV-2. Based on our findings there is no rationale to advise vitamin D optimization preceding SARS-CoV-2 vaccination in HCW with moderate vitamin D status.