Impact of pre-vaccination active vitamin D levels on COVID-19 mRNA vaccine-induced immunity in a Japanese cohort

BACKGROUND/OBJECTIVES: vitamin D, a bioactive form with steady blood concentrations, on vaccine response. METHODS: From June to September 2021, we measured active vitamin D levels in 88 Japanese workers and students before vaccination with BNT162b2 or mRNA-1273. We assessed SARS-CoV-2 spike protein S1 IgG and IgM levels and antigen-specific INF-γ-releasing cells from pre-vaccination up to 8 months post-second dose. RESULTS: Active vitamin D levels ranged from 33.7 to 99.8 pg/mL; 45.5% exceeded the Japanese standard limit of 60 pg/mL. No subjects had values below the lower limit of the reference range (20 pg/mL). In a mixed model accounting for repeated measures and sub-cohort random effects and following fixed effects, vaccine type, weeks post-vaccination, age, sex, ALDH2 gene polymorphism, height, smoking, ethanol intake, exercise, stress, steroid use, allergies, dyslipidemia, active vitamin D was negatively associated with anti-S1 IgG and IgM (p < 0.001) but positively with INF-γ-releasing cell counts (p = 0.003). CONCLUSIONS: The humoral and cellular immunogenicity of the SARS-CoV-2 vaccine is associated with baseline active vitamin D levels, oppositely. Considering the larger role of cellular immunity in preventing severe outcomes of SARS-CoV-2 infection, as well as its relative robustness against viral mutations, higher levels of active vitamin D than those in the reference range may be advantageous. However, despite the growing interest in deficiency, we failed to examine the association with low vitamin D levels.