Impact of ageing and a synbiotic on the immune response to seasonal influenza vaccination; a randomised controlled trial

Sumia Enani, Agnieszka Przemska-Kosicka, Caroline E Childs, Catherine Maidens, Honglin Dong, Lorenza Conterno, Kieran Tuohy, Susan Todd, Margot Gosney, Parveen Yaqoob, Sumia Enani, Agnieszka Przemska-Kosicka, Caroline E Childs, Catherine Maidens, Honglin Dong, Lorenza Conterno, Kieran Tuohy, Susan Todd, Margot Gosney, Parveen Yaqoob

Abstract

Background & aims: Ageing increases risk of respiratory infections and impairs the response to influenza vaccination. Pre- and pro-biotics offer an opportunity to modulate anti-viral defenses and the response to vaccination 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, on the B and T cell response to seasonal influenza vaccination in young and older subjects .

Methods: In a double-blind, randomized controlled trial, 58 young (18-35 y) and 54 older (60-85 y) subjects were supplemented with the synbiotic for 8 weeks. At 4 weeks they were administered with a seasonal influenza vaccine. B and T cell phenotype and responsiveness to in vitro re-stimulation with the vaccine were assessed at baseline, 4, 6 and 8 weeks.

Results: B and T cell profiles differed markedly between young and older subjects. Vaccination increased numbers of memory, IgA+ memory, IgG+ memory and total IgG+ B cells in young subjects, but failed to do so in older subjects and did not significantly alter T cell subsets. Seroconversion to the H1N1 subunit in the older subjects was associated with higher post-vaccination numbers of plasma B cells, but seroconversion was less consistently associated with T cell phenotype. B and T cell subsets from both young and older subjects demonstrated a strong antigen-specific recall challenge, and although not influenced by age, responsiveness to the recall challenge was associated with seroconversion. In older subjects, CMV seropositivity was associated with a significantly lower recall response to the vaccine, but the synbiotic did not affect the responsiveness of B or T cells to re-stimulation with influenza vaccine.

Conclusions: Antigen-specific B and T cell activation following an in vitro recall challenge with the influenza vaccine was influenced by CMV seropositivity, but not by a synbiotic. Registered under ClinicalTrials.gov Identifier no. NCT01066377.

Keywords: Ageing; Influenza; Lymphocyte; Probiotic; Vaccination.

Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
Recruitment flow diagram.
Fig. 2
Fig. 2
Study protocol.
Fig. 3
Fig. 3
Higher numbers of circulating plasma B cells are associated with seroconversion to H1N1 in the older cohort. Data are mean ± SE for n = 58 young and n = 54 older subjects. *Significantly different from non-seroconverters within the same age group (P < 0.01, independent t-test).
Fig. 4
Fig. 4
Higher numbers of regulatory T cells are associated with seroconversion to all subunits combined in the combined cohort. Data are mean ± SE for n = 58 young and n = 54 older subjects. *Denotes significantly different from non-seroconverters within the same age group (P < 0.01, independent t-test).
Fig. 5
Fig. 5
Effects of vaccination and synbiotic on numbers of IgG+ memory and IgG+ total B cells in older subjects. Data are mean ± SE for n = 54 older subjects. Numbers of IgG+ memory and IgG+ total B cells tended to increase in the older subjects receiving the synbiotic (■), but not in those receiving the placebo (□) (LMM, effect of treatment, older cohort, P = 0.068 and P = 0.09 respectively).
Fig. 6
Fig. 6
Effect of CMV seropositivity on responsiveness of B and T cells to in vitro re-stimulation with the influenza vaccine. Data are mean ± SE for n = 45 young (A) and n = 44 older (B) subjects. *Denotes significantly different from CMV− subjects (P < 0.01, independent t-test).

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