维生素D与乙肝疫苗应答：一项针对健康成年人的前瞻性队列研究以及一项随机、安慰剂对照的口服维生素D和模拟阳光补充试验。

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

作者信息

Kashi Daniel S, Oliver Samuel J, Wentz Laurel M, Roberts Ross, Carswell Alexander T, Tang Jonathan C Y, Jackson Sarah, Izard Rachel M, Allan Donald, Rhodes Lesley E, Fraser William D, Greeves Julie P, Walsh Neil P

机构信息

College of Human Sciences, Bangor University, Bangor, LL57 2PZ, UK.

Faculty of Science, Liverpool John Moores University, Liverpool, UK.

出版信息

Eur J Nutr. 2021 Feb;60(1):475-491. doi: 10.1007/s00394-020-02261-w. Epub 2020 May 10.

PURPOSE

To determine serum 25(OH)D and 1,25(OH)D 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 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 (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)D ≤ 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)D 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 .

目的

确定血清25(OH)D和1,25(OH)D与乙肝疫苗接种的关系（研究1）。然后，通过在冬季对模拟阳光和口服维生素D补充剂进行独特比较，研究实现维生素D充足（血清25(OH)D≥50 nmol/L）对乙肝疫苗接种的影响（研究2）。

方法

研究1纳入了447名成年人。在研究2中，初次接种乙肝疫苗3天后，119名男性分别接受安慰剂、模拟阳光照射（1.3倍标准红斑剂量，每周3次，共4周，然后每周1次，共8周）或口服维生素D（第1至4周每天1000 IU，第5至12周每天400 IU）。我们将乙肝疫苗接种效果衡量为抗乙肝表面抗原免疫球蛋白G≥10 mIU/mL的应答者百分比。

结果

在研究1中，维生素D水平低的人群疫苗应答较差（25(OH)D≤40对比41 - 71 nmol/L，平均差异[95%置信区间]-15%[-26, -3%]；1,25(OH)D≤120对比≥157 pmol/L，-12%[-24%, -1%]）。冬季的疫苗应答也比夏季差（-18%[-31%, -3%]），此时血清25(OH)D和1,25(OH)D处于季节性最低点，81%的人血清25(OH)D<50 nmol/L。在研究2中，维生素D补充策略在使几乎所有（约95%）人从冬季维生素D最低点达到维生素D充足方面同样有效；然而，在初次接种疫苗3天后开始补充并没有影响疫苗应答（维生素D对比安慰剂4%[-21%, 14%]）。