BCG vaccination: a role for vitamin D?

Abstract

Background: BCG vaccination is administered in infancy in most countries with the aim of providing protection against tuberculosis. There is increasing interest in the role of vitamin D in immunity to tuberculosis. This study objective was to determine if there was an association between circulating 25(OH)D concentrations and BCG vaccination status and cytokine responses following BCG vaccination in infants.

Methods: Blood samples were collected from UK infants who were vaccinated with BCG at 3 (n = 47) and 12 (n = 37) months post BCG vaccination. These two time-points are denoted as time-point 1 and time-point 2. Two blood samples were also collected from age-matched unvaccinated infants (n = 32 and 28 respectively), as a control group. Plasma vitamin D concentrations (25(OH)D) were measured by radio-immunoassay. The cytokine IFNγ was measured in supernatants from diluted whole blood stimulated with M.tuberculosis (M.tb) PPD for 6 days.

Results: 58% of infants had some level of hypovitaminosis (25(OH)D <30 ng/ml) at time-point 1, and this increased to 97% 9 months later. BCG vaccinated infants were almost 6 times (CI: 1.8-18.6) more likely to have sufficient vitamin D concentrations than unvaccinated infants at time-point 1, and the association remained strong after controlling for season of blood collection, ethnic group and sex. Among vaccinees, there was also a strong inverse association between IFNγ response to M.tb PPD and vitamin D concentration, with infants with higher vitamin D concentrations having lower IFNγ responses.

Conclusions: Vitamin D may play an immuno-regulatory role following BCG vaccination. The increased vitamin D concentrations in BCG vaccinated infants could have important implications: vitamin D may play a role in immunity induced by BCG vaccination and may contribute to non-specific effects observed following BCG vaccination.

Figure 1. Histograms of 25(OH)D at time-point 1 and 2.

25(OH)D was measured in plasma samples from infants 3 and 12 months post BCG vaccination, and in age-matched unvaccinated controls. 25(OH)D in BCG vaccinated and unvaccinated infants a] in vaccinated infants and unvaccinated controls combined at time-point 1 and b] in vaccinated infants and unvaccinated controls combined at time-point 2; 25(OH)D in infants grouped according to BCG vaccination status at c] time-point 1 and d] time-point 2.

Figure 2. Association of IFNγ to M.tb PPD with 25(OH)D concentrations 3 months post BCG vaccination.

25 (OH) D was measured in plasma samples and IFNγ to M.tb PPD was measured by ELISA from supernatants from 6 day cultures of diluted whole blood from infants 3 months post BCG vaccination. a] Dot plot where individuals are represented by dots, and lines represents linear fit of responses b] Histograms of IFNγ response to M.tb PPD response in infants with hypovitaminosis (<30 ng/ml) and in infants with sufficient 25(OH)D.