Vitamin D and the hepatitis B vaccine response: A prospective cohort study and a randomized, placebo-controlled oral vitamin D₃ and simulated sunlight supplementation trial in healthy adults

Purpose: To determine serum 25(OH)D and 1,25(OH) ₂D relationship with hepatitis B vaccination (study 1). Then, to investigate the effects on hepatitis B vaccination of achieving vitamin D sufficiency (serum 25(OH)D ≥ 50 nmol/L) by a unique comparison of simulated sunlight and oral vitamin D ₃ supplementation in wintertime (study 2). Methods: Study 1 involved 447 adults. In study 2, 3 days after the initial hepatitis B vaccination, 119 men received either placebo, simulated sunlight (1.3 × standard-erythema dose, 3 × /week for 4 weeks and then 1 × /week for 8 weeks) or oral vitamin D ₃ (1000 IU/day for 4 weeks and 400 IU/day for 8 weeks). We measured hepatitis B vaccination efficacy as percentage of responders with anti-hepatitis B surface antigen immunoglobulin G ≥ 10 mIU/mL. Results: In study 1, vaccine response was poorer in persons with low vitamin D status (25(OH)D ≤ 40 vs 41–71 nmol/L mean difference [95% confidence interval] − 15% [− 26, − 3%]; 1,25(OH) ₂D ≤ 120 vs ≥ 157 pmol/L − 12% [− 24%, − 1%]). Vaccine response was also poorer in winter than summer (− 18% [− 31%, − 3%]), when serum 25(OH)D and 1,25(OH) ₂D were at seasonal nadirs, and 81% of persons had serum 25(OH)D < 50 nmol/L. In study 2, vitamin D supplementation strategies were similarly effective in achieving vitamin D sufficiency from the winter vitamin D nadir in almost all (~ 95%); however, the supplementation beginning 3 days after the initial vaccination did not effect the vaccine response (vitamin D vs placebo 4% [− 21%, 14%]). Conclusion: Low vitamin D status at initial vaccination was associated with poorer hepatitis B vaccine response (study 1); however, vitamin D supplementation commencing 3 days after vaccination (study 2) did not influence the vaccination response. Clinical trial registry number: Study 1 NCT02416895; https://clinicaltrials.gov/ct2/show/study/NCT02416895; Study 2 NCT03132103; https://clinicaltrials.gov/ct2/show/NCT03132103.