Age-Related Changes in the Natural Killer Cell Response to Seasonal Influenza Vaccination Are Not Influenced by a Synbiotic: a Randomised Controlled Trial

Abstract

Natural killer (NK) cells are an important component of the immune response to influenza infection, but are subject to alteration during aging, which may play a role in impaired response to infection and vaccination in older people. Enhancement of NK cell activity could, therefore, present a means to improve the immune response to vaccination in older subjects, and pre- and probiotics offer an opportunity to modulate antiviral defenses via alteration of the gut microbiota. This study investigated the effect of a novel probiotic, Bifidobacterium longum bv. infantis CCUG 52486, combined with a prebiotic, gluco-oligosaccharide (B. longum + Gl-OS), on the NK cell response to seasonal influenza vaccination in young and older subjects in a double-blind, randomized controlled trial. There were significant effects of aging on NK cell phenotype, the most notable of which were an increase in CD56dim cells, mainly reflected in the CD16+ subset, a decrease in CD56bright cells, mainly reflected in the CD16- subset, and greater expression of the immunosenescence marker, CD57, on NK cell subsets. However, these changes only partially translated to differences in NK cell activity, observed as trends toward reduced NK cell activity in older subjects when analyzed on a per cell basis. Influenza vaccination increased the proportion of CD56bright cells and decreased the proportion of CD56dim cells, in young, but not older subjects. Although NK cell activity in response to vaccination was not significantly different between the young and older subjects, low post-vaccination NK cell activity was associated with poor seroconversion in only the older subjects. There was no influence of the synbiotic on NK cell phenotype or activity, either before or after influenza vaccination. In conclusion, aging is associated with marked alteration of the phenotype of the NK cell population and there was evidence of an impaired NK cell response to influenza vaccination in older subjects. The effects of aging on NK cell phenotype and activity could not be offset by B. longum + Gl-OS.

Clinical trial registration: www.ClinicalTrials.gov, identifier NCT01066377.

Keywords: aging; influenza; prebiotic; probiotic; vaccination.

Figures

Figure 1

CMV seropositivity is associated with an increase in CD57+CD3+CD56+NKT cells. Data are % of CD57+CD3+CD56+ NKT cells ± SEM for n = 40 young and n = 41 older subjects, ▫CMV−, ▪CMV+. Data were analyzed using independent samples t-test. *Denotes significant difference between CMV and CMV+ status in young (P < 0.001) and older subjects (P < 0.01).

Figure 2

Baseline natural killer cell activity. Data are mean ± SEM at week 0, for n = 54 subjects per group. Data were analyzed using independent samples t-test (2-tailed). P = 0.11 for E/T ratio 100:1, P = 0.54 for 50:1, P = 0.03 for 25:1, and P = 0.08 for 12.5:1.

Figure 3

Baseline natural killer cell activity on a per cell basis. Data are mean ± SEM at week 0, for n = 54 subjects per group. Data were analyzed using independent samples t-test (2-tailed). P = 0.02 for E/T ratio 100:1, P = 0.03 for 50:1, P = 0.038 for 25:1, and P = 0.116 for 12.5:1.