Abstract
PurposeTo 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 D3 supplementation in wintertime (study 2).MethodsStudy 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 D3 (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.ResultsIn 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%]).ConclusionLow 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 numberStudy 1 NCT02416895; https://clinicaltrials.gov/ct2/show/study/NCT02416895; Study 2 NCT03132103; https://clinicaltrials.gov/ct2/show/NCT03132103.
Highlights
Discovery of the vitamin D receptor in almost all immune cells, and the many roles vitamin D has in innate and adaptive arms of immunity [1,2,3], highlight the importance of vitamin D in the regulation of immune responses [4]
Fewer participants tended to respond to the hepatitis B vaccination who had 25(OH) D < 50 nmol/L than those who were vitamin D sufficient at the time of initial vaccination (50% vs 58%, mean difference [95% confidence interval], − 8% [− 17%, 1%], P = 0.09, h = 0.16, Fig. 3a)
Fewer participants were hepatitis B vaccine responders when they presented with low serum 1,25(OH)2D compared to participants who presented with high serum 1,25(OH)2D at the time of initial vaccination
Summary
Discovery of the vitamin D receptor in almost all immune cells, and the many roles vitamin D has in innate and adaptive arms of immunity [1,2,3], highlight the importance of vitamin D in the regulation of immune responses [4]. Hepatitis B vaccination has previously been shown to be influenced by genetics and lifestyle factors [13,14,15] with 10–15% of adults responding inadequately by producing too few antibodies, as dictated by an anti-hepatitis B surface antigen immunoglobulin G (IgG) concentration of less than 10 mIU/mL [16]. Those responding to the vaccination with IgG concentration of 10 mIU/ mL or more are generally accepted to be protected against infection clinically [16, 17]. The hepatitis B vaccination course presents a suitable model to study the influence of vitamin D on the secondary immune response because there is widespread inter-individual variability in the magnitude of the antibody response after the second vaccination, and it is more possible to control prior exposure than with other commonly experienced vaccines (e.g., influenza) [24]
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