Skip to main content
Top
Published in: Immunity & Ageing 1/2016

Open Access 01-12-2016 | Research

Effect of a synbiotic on the response to seasonal influenza vaccination is strongly influenced by degree of immunosenescence

Authors: Agnieszka Przemska-Kosicka, Caroline E. Childs, Sumia Enani, Catherine Maidens, Honglin Dong, Iman Bin Dayel, Kieran Tuohy, Susan Todd, Margot A. Gosney, Parveen Yaqoob

Published in: Immunity & Ageing | Issue 1/2016

Login to get access

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 (CD28CD57+) 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 CD28CD57+ 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.

Trial registration

Clinicaltrials.gov NCT01066377.
Appendix
Available only for authorised users
Literature
1.
go back to reference Haq K, McElhaney JE. Immunosenescence: influenza vaccination and the elderly. Curr Opin Immunol. 2014;29:38–42.CrossRefPubMed Haq K, McElhaney JE. Immunosenescence: influenza vaccination and the elderly. Curr Opin Immunol. 2014;29:38–42.CrossRefPubMed
5.
go back to reference MacDonald TT, Bell I. Probiotics and the immune response to vaccines. Proc Nutr Soc. 2010;69:442–6.CrossRefPubMed MacDonald TT, Bell I. Probiotics and the immune response to vaccines. Proc Nutr Soc. 2010;69:442–6.CrossRefPubMed
6.
go back to reference Maidens C, Childs C, Przemska A, et al. Modulation of vaccine response by concomitant probiotic administration. Br J Clin Pharmacol. 2013;75:663–70.PubMedPubMedCentral Maidens C, Childs C, Przemska A, et al. Modulation of vaccine response by concomitant probiotic administration. Br J Clin Pharmacol. 2013;75:663–70.PubMedPubMedCentral
7.
go back to reference Lomax AR, Calder PC. Prebiotics, immune function, infection and inflammation: a review of the evidence. Br J Nutr. 2009;101:633–58.CrossRefPubMed Lomax AR, Calder PC. Prebiotics, immune function, infection and inflammation: a review of the evidence. Br J Nutr. 2009;101:633–58.CrossRefPubMed
8.
go back to reference Biagi E, Candela M, Turroni S, et al. Ageing and gut microbes: perspectives for health maintenance and longevity. Pharmacol Res. 2013;69:11–20.CrossRefPubMed Biagi E, Candela M, Turroni S, et al. Ageing and gut microbes: perspectives for health maintenance and longevity. Pharmacol Res. 2013;69:11–20.CrossRefPubMed
9.
go back to reference Dominguez-Bello MG, Blaser MJ, Ley RE, Knight R. Development of the human gastrointestinal microbiota and insights from high-throughput sequencing. Gastroenterology. 2011;140:1713–9.CrossRefPubMed Dominguez-Bello MG, Blaser MJ, Ley RE, Knight R. Development of the human gastrointestinal microbiota and insights from high-throughput sequencing. Gastroenterology. 2011;140:1713–9.CrossRefPubMed
10.
go back to reference Silvi S, Verdenelli MC, Orpianesi C, Cresci A. EU project Crownalife: functional foods, gut microflora and healthy ageing - Isolation and identification of Lactobacillus and Bifidobacterium strains from faecal samples of elderly subjects for a possible probiotic use in functional foods. J Food Eng. 2003;56:195–200.CrossRef Silvi S, Verdenelli MC, Orpianesi C, Cresci A. EU project Crownalife: functional foods, gut microflora and healthy ageing - Isolation and identification of Lactobacillus and Bifidobacterium strains from faecal samples of elderly subjects for a possible probiotic use in functional foods. J Food Eng. 2003;56:195–200.CrossRef
11.
go back to reference Likotrafiti EMKSF, F.; Tuohy, K.M.; Gibson, G.R.; Rastall, R.A. Molecular identification and anti-pathogenic activities of putative probiotic bacteria isolated from faeces of healthy elderly adults. Microbial Ecology in Health and Disease 2004; 16:8. Likotrafiti EMKSF, F.; Tuohy, K.M.; Gibson, G.R.; Rastall, R.A. Molecular identification and anti-pathogenic activities of putative probiotic bacteria isolated from faeces of healthy elderly adults. Microbial Ecology in Health and Disease 2004; 16:8.
12.
go back to reference You J, Yaqoob P. Evidence of immunomodulatory effects of a novel probiotic, Bifidobacterium longum bv. infantis CCUG 52486. FEMS Immunol Med Microbiol. 2012;66:353–62.CrossRefPubMed You J, Yaqoob P. Evidence of immunomodulatory effects of a novel probiotic, Bifidobacterium longum bv. infantis CCUG 52486. FEMS Immunol Med Microbiol. 2012;66:353–62.CrossRefPubMed
14.
go back to reference Goodwin K, Viboud C, Simonsen L. Antibody response to influenza vaccination in the elderly: A quantitative review. Vaccine. 2006;24:1159–69.CrossRefPubMed Goodwin K, Viboud C, Simonsen L. Antibody response to influenza vaccination in the elderly: A quantitative review. Vaccine. 2006;24:1159–69.CrossRefPubMed
15.
16.
go back to reference Kovaiou RD, Herndler-Brandstetter D, Grubeck-Loebenstein B. Age-related changes in immunity: implications for vaccination in the elderly. Expert Rev Mol Med. 2007;9:1–17.CrossRefPubMed Kovaiou RD, Herndler-Brandstetter D, Grubeck-Loebenstein B. Age-related changes in immunity: implications for vaccination in the elderly. Expert Rev Mol Med. 2007;9:1–17.CrossRefPubMed
17.
go back to reference Bunout D, Barrera G, Hirsch S, et al. Effects of a nutritional supplement on the immune response and cytokine production in free-living Chilean elderly. JPEN J Parenter Enteral Nutr. 2004;28:348–54.CrossRefPubMed Bunout D, Barrera G, Hirsch S, et al. Effects of a nutritional supplement on the immune response and cytokine production in free-living Chilean elderly. JPEN J Parenter Enteral Nutr. 2004;28:348–54.CrossRefPubMed
18.
go back to reference Boge T, Remigy M, Vaudaine S, et al. A probiotic fermented dairy drink improves antibody response to influenza vaccination in the elderly in two randomised controlled trials. Vaccine. 2009;27:5677–84.CrossRefPubMed Boge T, Remigy M, Vaudaine S, et al. A probiotic fermented dairy drink improves antibody response to influenza vaccination in the elderly in two randomised controlled trials. Vaccine. 2009;27:5677–84.CrossRefPubMed
19.
go back to reference Namba K, Hatano M, Yaeshima T, et al. Effects of Bifidobacterium longum BB536 administration on influenza infection, influenza vaccine antibody titer, and cell-mediated immunity in the elderly. Biosci Biotechnol Biochem. 2010;74:939–45.CrossRefPubMed Namba K, Hatano M, Yaeshima T, et al. Effects of Bifidobacterium longum BB536 administration on influenza infection, influenza vaccine antibody titer, and cell-mediated immunity in the elderly. Biosci Biotechnol Biochem. 2010;74:939–45.CrossRefPubMed
20.
go back to reference Van Puyenbroeck K, Hens N, Coenen S, et al. Efficacy of daily intake of Lactobacillus casei Shirota on respiratory symptoms and influenza vaccination immune response: a randomized, double-blind, placebo-controlled trial in healthy elderly nursing home residents. Am J Clin Nutr. 2012;95:1165–71.CrossRefPubMed Van Puyenbroeck K, Hens N, Coenen S, et al. Efficacy of daily intake of Lactobacillus casei Shirota on respiratory symptoms and influenza vaccination immune response: a randomized, double-blind, placebo-controlled trial in healthy elderly nursing home residents. Am J Clin Nutr. 2012;95:1165–71.CrossRefPubMed
21.
go back to reference Isolauri E, Joensuu J, Suomalainen H, et al. Improved Immunogenicity of Oral Dxrrv Reassortant Rotavirus Vaccine by Lactobacillus-Casei Gg. Vaccine. 1995;13:310–2.CrossRefPubMed Isolauri E, Joensuu J, Suomalainen H, et al. Improved Immunogenicity of Oral Dxrrv Reassortant Rotavirus Vaccine by Lactobacillus-Casei Gg. Vaccine. 1995;13:310–2.CrossRefPubMed
22.
go back to reference de Vrese M, Winkler P, Rautenberg P, et al. Probiotic bacteria reduced duration and severity but not the incidence of common cold episodes in a double blind, randomized, controlled trial. Vaccine. 2006;24:6670–4.CrossRefPubMed de Vrese M, Winkler P, Rautenberg P, et al. Probiotic bacteria reduced duration and severity but not the incidence of common cold episodes in a double blind, randomized, controlled trial. Vaccine. 2006;24:6670–4.CrossRefPubMed
23.
go back to reference Olivares M, Diaz-Ropero MP, Sierra S, et al. Oral intake of Lactobacillus fermentum CECT5716 enhances the effects of influenza vaccination. Nutrition. 2007;23:254–60.CrossRefPubMed Olivares M, Diaz-Ropero MP, Sierra S, et al. Oral intake of Lactobacillus fermentum CECT5716 enhances the effects of influenza vaccination. Nutrition. 2007;23:254–60.CrossRefPubMed
24.
go back to reference Bosch M, Mendez M, Perez M, et al. Lactobacillus plantarum CECT7315 and CECT7316 stimulate immunoglobulin production after influenza vaccination in elderly. Nutricion hospitalaria: organo oficial de la Sociedad Espanola de Nutricion Parenteral y Enteral. 2012;27:504–9. Bosch M, Mendez M, Perez M, et al. Lactobacillus plantarum CECT7315 and CECT7316 stimulate immunoglobulin production after influenza vaccination in elderly. Nutricion hospitalaria: organo oficial de la Sociedad Espanola de Nutricion Parenteral y Enteral. 2012;27:504–9.
25.
go back to reference Rizzardini G, Eskesen D, Calder PC, et al. Evaluation of the immune benefits of two probiotic strains Bifidobacterium animalis ssp. lactis, BB-12(R) and Lactobacillus paracasei ssp. paracasei, L. casei 431(R) in an influenza vaccination model: a randomised, double-blind, placebo-controlled study. Br J Nutr. 2012;107:876–84.CrossRefPubMed Rizzardini G, Eskesen D, Calder PC, et al. Evaluation of the immune benefits of two probiotic strains Bifidobacterium animalis ssp. lactis, BB-12(R) and Lactobacillus paracasei ssp. paracasei, L. casei 431(R) in an influenza vaccination model: a randomised, double-blind, placebo-controlled study. Br J Nutr. 2012;107:876–84.CrossRefPubMed
26.
go back to reference You J, Dong H, Mann ER, et al. Ageing impairs the T cell response to dendritic cells. Immunobiology. 2013;218:1077–84.CrossRefPubMed You J, Dong H, Mann ER, et al. Ageing impairs the T cell response to dendritic cells. Immunobiology. 2013;218:1077–84.CrossRefPubMed
27.
go back to reference Likotrafiti E, Manderson KS, Fava F, Tuohy KM, Gibson GR, Rastall RA. Molecular identification and anti-pathogenic activities of putative probiotic bacteria isolated from faeces of healthy elderly individuals. Microb Ecol Health Dis. 2004;16:105–12.CrossRef Likotrafiti E, Manderson KS, Fava F, Tuohy KM, Gibson GR, Rastall RA. Molecular identification and anti-pathogenic activities of putative probiotic bacteria isolated from faeces of healthy elderly individuals. Microb Ecol Health Dis. 2004;16:105–12.CrossRef
28.
go back to reference Vallejo AN. Immune remodeling: lessons from repertoire alterations during chronological aging and in immune-mediated disease. Trends Mol Med. 2007;13:94–102.CrossRefPubMed Vallejo AN. Immune remodeling: lessons from repertoire alterations during chronological aging and in immune-mediated disease. Trends Mol Med. 2007;13:94–102.CrossRefPubMed
29.
go back to reference Derhovanessian E, Maier AB, Hahnel K, et al. Latent Infection with Cytomegalovirus Is Associated with Poor Memory CD4 Responses to Influenza A Core Proteins in the Elderly. J Immunol. 2014;193:3624–31.CrossRefPubMed Derhovanessian E, Maier AB, Hahnel K, et al. Latent Infection with Cytomegalovirus Is Associated with Poor Memory CD4 Responses to Influenza A Core Proteins in the Elderly. J Immunol. 2014;193:3624–31.CrossRefPubMed
30.
go back to reference Frei R, Akdis M, O’Mahony L. Prebiotics, probiotics, synbiotics, and the immune system: experimental data and clinical evidence. Curr Opin Gastroen. 2015;31:153–8.CrossRef Frei R, Akdis M, O’Mahony L. Prebiotics, probiotics, synbiotics, and the immune system: experimental data and clinical evidence. Curr Opin Gastroen. 2015;31:153–8.CrossRef
31.
go back to reference Ligthart GJ, Corberand JX, Fournier C, et al. Admission criteria for immunogerontological studies in man: the SENIEUR protocol. Mech Ageing Dev. 1984;28:47–55.CrossRefPubMed Ligthart GJ, Corberand JX, Fournier C, et al. Admission criteria for immunogerontological studies in man: the SENIEUR protocol. Mech Ageing Dev. 1984;28:47–55.CrossRefPubMed
32.
go back to reference Hudon C, Fortin A, Vanasse A. Cumulative Illness Rating Scale was a reliable and valid index in a family practice context. J Clin Epidemiol. 2005;58:603–8.CrossRefPubMed Hudon C, Fortin A, Vanasse A. Cumulative Illness Rating Scale was a reliable and valid index in a family practice context. J Clin Epidemiol. 2005;58:603–8.CrossRefPubMed
33.
go back to reference Davidson LE, Fiorino AM, Snydman DR, Hibberd PL. Lactobacillus GG as an immune adjuvant for live-attenuated influenza vaccine in healthy adults: a randomized double-blind placebo-controlled trial. Eur J Clin Nutr. 2011;65:501–7.CrossRefPubMedPubMedCentral Davidson LE, Fiorino AM, Snydman DR, Hibberd PL. Lactobacillus GG as an immune adjuvant for live-attenuated influenza vaccine in healthy adults: a randomized double-blind placebo-controlled trial. Eur J Clin Nutr. 2011;65:501–7.CrossRefPubMedPubMedCentral
34.
go back to reference Sarbini SR, Kolida S, Gibson GR, Rastall RA. In vitro fermentation of commercial alpha-gluco-oligosaccharide by faecal microbiota from lean and obese human subjects. Br J Nutr. 2013;109:1980–9.CrossRefPubMed Sarbini SR, Kolida S, Gibson GR, Rastall RA. In vitro fermentation of commercial alpha-gluco-oligosaccharide by faecal microbiota from lean and obese human subjects. Br J Nutr. 2013;109:1980–9.CrossRefPubMed
35.
36.
go back to reference Costabile A, Kolida S, Klinder A, et al. A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke (Cynara scolymus) in healthy human subjects. British J Nutr. 2010;104:1007–17.CrossRef Costabile A, Kolida S, Klinder A, et al. A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke (Cynara scolymus) in healthy human subjects. British J Nutr. 2010;104:1007–17.CrossRef
Metadata
Title
Effect of a synbiotic on the response to seasonal influenza vaccination is strongly influenced by degree of immunosenescence
Authors
Agnieszka Przemska-Kosicka
Caroline E. Childs
Sumia Enani
Catherine Maidens
Honglin Dong
Iman Bin Dayel
Kieran Tuohy
Susan Todd
Margot A. Gosney
Parveen Yaqoob
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Immunity & Ageing / Issue 1/2016
Electronic ISSN: 1742-4933
DOI
https://doi.org/10.1186/s12979-016-0061-4

Other articles of this Issue 1/2016

Immunity & Ageing 1/2016 Go to the issue