Does Vitamin D Deficiency Affect the Immunogenic Responses to Influenza Vaccination? A Systematic Review and Meta-Analysis

Abstract

Influenza virus infection is a major global public health problem, and the efficacy of influenza vaccination is not satisfactory. Vitamin D is involved in many immune-mediated inflammatory processes. The impact of vitamin D levels on the immunogenic response to influenza vaccination is not clear. We performed a comprehensive literature search and systematic review of studies that investigated vitamin D and influenza vaccination. Data pertaining to study population, vaccine components, vitamin D levels, and immunogenic response were analyzed. Nine studies, with a combined study population of 2367 patients, were included in the systematic review. Four studies were included in the meta-analysis to investigate the influence of vitamin D deficiency (VDD) on the seroprotection (SP) rates and seroconversion (SC) rates following influenza vaccination. We found no significant association between vitamin D level and the immunogenic response to influenza vaccination. However, strain-specific differences may exist. We observed lower SP rates of influenza A virus subtype H3N2 (A/H3N2) and B strain in VDD patients than patients with normal vitamin D levels (A/H3N2: 71.8% vs. 80.1%, odds ratio (OR): 0.63, 95% confidence interval (CI): 0.43-0.91, p = 0.01; B strain: 69.6% vs. 76.4%, OR: 0.68, 95% CI: 0.5-0.93, p = 0.01). However, the SP rates of A/H1N1 and SC rates of all three strains were not significantly different in VDD and control groups. In conclusion, no association was observed between VDD and immunogenic response to influenza vaccination.

Keywords: 25(OH)D; calcitriol; human health; influenza; influenza vaccination; vitamin D.

Figure 1

Schematic illustration of the literature search and the study-selection criteria. CINAHL = the Cumulative Index to Nursing and Allied Health; Airiti = Art Image Indexing Service on the Internet Database; NTLTD = the National Digital Library of Theses and Dissertations in Taiwan.

Figure 2

Forrest plot of the SP rates of influenza vaccination in the VDD (vitamin D deficiency) and placebo groups. (a) Strain A/H1N1; (b) strain A/H3N2; (c) strain B. df = degrees of freedom; def = deficiency; M-H = Mantel-Haenszel.

Figure 3

Forrest plot of the seroconversion (SC) rates of influenza vaccination in the VDD and placebo groups. (a) Strain A/H1N1; (b) strain A/H3N2; (c) strain B.