title: Effect of a synbiotic on the response to seasonal influenza vaccination is strongly influenced by degree of immunosenescence.
abstract: BACKGROUND
  Ageing increases risk of respiratory infections and impairs the response to influenza vaccination. Pre- and probiotics 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 52,486, combined with a prebiotic, gluco-oligosaccharide (B. longum + Gl-OS), on the response to seasonal influenza vaccination in young and older subjects in a double-blind, randomized controlled trial, taking into account the influence of immunosenescence markers at baseline.
  
  
  RESULTS
  Vaccination resulted in a significant increase in total antibody titres, vaccine-specific IgA, IgM and IgG and seroprotection to all three subunits of the vaccine in both young and older subjects, and in general, the increases in young subjects were greater. There was little effect of the synbiotic, although it tended to reduce seroconversion to the Brisbane subunit of the vaccine and the vaccine-specific IgG response in older subjects. Immunological characterization revealed that older subjects randomized to the synbiotic had a significantly higher number of senescent (CD28(-)CD57(+)) helper T cells at baseline compared with those randomized to the placebo, and they also had significantly higher plasma levels of anti-CMV IgG and a greater tendency for CMV seropositivity. Moreover, higher numbers of CD28(-)CD57(+) helper T cells were associated with failure to seroconvert to Brisbane, strongly suggesting that the subjects randomized to the synbiotic were already at a significant disadvantage in terms of likely ability to respond to the vaccine compared with those randomized to the placebo.
  
  
  CONCLUSIONS
  Ageing was associated with marked impairment of the antibody response to influenza vaccination in older subjects and the synbiotic failed to reverse this impairment. However, the older subjects randomized to the synbiotic were at a significant disadvantage due to a greater degree of immunosenscence at baseline compared with those randomized to the placebo. Thus, baseline differences in immunosenescence between the randomized groups are likely to have influenced the outcome of the intervention, highlighting the need for detailed immunological characterization of subjects prior to interventions.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT01066377.
authors.affiliation: Department of Food and Nutritional Sciences, University of Reading, PO Box 226, Whiteknights, Reading, Berkshire RG6 6AP UK.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Przemska-Kosicka
authors.affiliation: Department of Food and Nutritional Sciences, University of Reading, PO Box 226, Whiteknights, Reading, Berkshire RG6 6AP UK.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Childs
authors.affiliation: Department of Food and Nutritional Sciences, University of Reading, PO Box 226, Whiteknights, Reading, Berkshire RG6 6AP UK.
authors.forename: Sumia
authors.initials: S
authors.lastname: Enani
authors.affiliation: Department of Food and Nutritional Sciences, University of Reading, PO Box 226, Whiteknights, Reading, Berkshire RG6 6AP UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Maidens
authors.affiliation: Department of Food and Nutritional Sciences, University of Reading, PO Box 226, Whiteknights, Reading, Berkshire RG6 6AP UK.
authors.forename: Honglin
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Food and Nutritional Sciences, University of Reading, PO Box 226, Whiteknights, Reading, Berkshire RG6 6AP UK.
authors.forename: Iman Bin
authors.initials: IB
authors.lastname: Dayel
authors.affiliation: Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, via E. Mach, 1, San Michele all'Adige, Trento, 38010 Italy.
authors.forename: Kieran
authors.initials: K
authors.lastname: Tuohy
authors.affiliation: Department of Mathematics and Statistics, University of Reading, Reading, RG6 6AP UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Todd
authors.affiliation: Department of Food and Nutritional Sciences, University of Reading, PO Box 226, Whiteknights, Reading, Berkshire RG6 6AP UK.
authors.forename: Margot A
authors.initials: MA
authors.lastname: Gosney
authors.affiliation: Department of Food and Nutritional Sciences, University of Reading, PO Box 226, Whiteknights, Reading, Berkshire RG6 6AP UK.
authors.forename: Parveen
authors.initials: P
authors.lastname: Yaqoob
keywords: Ageing; Influenza; Prebiotic; Probiotic; Vaccination