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Immunonutrient Supplementation

Clinical Trial ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.00065

Impact of vitamin D supplementation on influenza vaccine response and immune functions in deficient elderly persons: a randomized placebo-controlled trial

 Nicolas Goncalves-Mendes1, 2, Jérémie Talvas2, Christian Dualé3, Aline Guttmann4, Violaine Corbin4, Geoffroy Marceau5, Vincent Sapin5, Patrick Brachet2, Bertrand Evrard2, 6, Henri Laurichesse2, 4 and Marie-Paule Vasson2, 4, 7*
  • 1Université Clermont Auvergne, France
  • 2INRA UMR1019 Unité de Nutrition Humaine est une unité mixte de recherches, France
  • 3INSERM CIC1405 CIC Clermont Ferrand, France
  • 4Centre Hospitalier Universitaire de Clermont-Ferrand, France
  • 5Service de Biochimie et Biologie Moléculaire, Centre Hospitalier Universitaire de Clermont-Ferrand, France
  • 6Service d'Immunologie, Centre Hospitalier Universitaire de Clermont-Ferrand, France
  • 7Centre Jean Perrin, France

Background: Immunosenescence contributes to reduced vaccine response in elderly persons, and is worsened by deficiencies in nutrients such as Vitamin (Vit-D). The immune system is a well-known target of Vit-D, which can both potentiate the innate immune response and inhibit the adaptive system, and so modulate vaccination response.
Objective: This randomized placebo-controlled double-blind trial investigated whether Vit-D supplementation in deficient elderly persons could improve influenza seroprotection and immune response.
Design: Deficient volunteers (Vit-D serum < 30 ng/mL) were assigned (V1) to receive either 100,000 IU/15 days of cholecalciferol (D, n = 19), or a placebo (P, n = 19), over a three month period. Influenza vaccination was performed at the end of this period (V2), and the vaccine response was evaluated 28 days later (V3). At each visit, serum cathelicidin, immune response to vaccination, plasma cytokines, lymphocyte phenotyping and phagocyte ROS production were assessed.
Results: Levels of serum 25-(OH)D increased after supplementation (D group, V1 vs V2: 20.7 ± 5.7 vs 44.3 ± 8.6 ng/mL, p < 0.001). No difference was observed for serum cathelicidin levels, antibody titers and ROS production in D vs P groups at V3. Lower plasma levels of TNFα (p = 0.040) and IL-6 (p = 0.046), and higher ones for TFGβ (p = 0.0028) were observed at V3. The Th1/Th2 ratio was lower in the D group at V2 (D: 0.12 ± 0.05 vs P: 0.18 ± 0.05, p = 0.039).
Conclusions: Vit-D supplementation promotes a higher TGFβ plasma level in response to influenza vaccination without improving antibody production. This supplementation seems to direct the lymphocyte polarization towards a tolerogenic immune response. A deeper characterization of metabolic and molecular pathways of these observations will aid in the understanding of Vit-D's effects on cell-mediated immunity in aging. This clinical trial was registered at as NCT01893385.

Keywords: vitamin-D deficiency, influenza vaccination, Aging, cathelicidin (LL-37), cytokine, Leukocyte phenotyping, randomized trial

Received: 07 Sep 2018; Accepted: 11 Jan 2019.

Edited by:

Thea Magrone, Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari, Italy

Reviewed by:

Yaqing Qie, Mayo Clinic Florida, United States
Per Wändell, Karolinska Institute (KI), Sweden  

Copyright: © 2019 Goncalves-Mendes, Talvas, Dualé, Guttmann, Corbin, Marceau, Sapin, Brachet, Evrard, Laurichesse and Vasson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Marie-Paule Vasson, INRA UMR1019 Unité de Nutrition Humaine est une unité mixte de recherches, Villeurbanne, France,