1. Metformin-induced suppression of IFN-α via mTORC1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes.
- Author
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Saenwongsa W, Nithichanon A, Chittaganpitch M, Buayai K, Kewcharoenwong C, Thumrongwilainet B, Butta P, Palaga T, Takahashi Y, Ato M, and Lertmemongkolchai G
- Subjects
- Aged, Antibodies, Viral immunology, Antibody Affinity immunology, Diabetes Mellitus, Type 2 drug therapy, Female, Glyburide pharmacology, Glyburide therapeutic use, Hemagglutination Inhibition Tests, Humans, Immunoglobulin G metabolism, Influenza A Virus, H1N1 Subtype drug effects, Influenza A Virus, H1N1 Subtype immunology, Influenza A Virus, H3N2 Subtype drug effects, Influenza A Virus, H3N2 Subtype immunology, Influenza B virus drug effects, Influenza B virus immunology, Influenza Vaccines immunology, Male, Metformin therapeutic use, Monocytes drug effects, Monocytes metabolism, Virion drug effects, Virion immunology, Antibody Formation drug effects, Diabetes Mellitus, Type 2 immunology, Interferon-alpha pharmacology, Mechanistic Target of Rapamycin Complex 1 metabolism, Metformin pharmacology, Seasons, Signal Transduction drug effects, Vaccination
- Abstract
Diabetes mellitus (DM) patients are at an increased risk of complications following influenza-virus infection, seasonal vaccination (SV) is recommended. However, SV with trivalent influenza vaccine (TIV) can induce antibody and type-I interferon (IFN) responses, and the effect of anti-DM treatment on these responses is incompletely understood. We evaluated the antibody response and IFN-α expression in individuals with and without type 2 DM (T2DM) following SV, and examined the effects on anti-DM treatment. TIV elicited sero-protection in all groups, but antibody persistency was <8 months, except for the antibody response to B-antigens in non-DM. T2DM impaired the IgG avidity index, and T2DM showed a significantly decreased response against H1N1 and H3N2, in addition to delaying and reducing haemagglutination-inhibition persistency against influenza B-antigens in DM groups treated with metformin (Met-DM) or glibenclamide (GB-DM). Following TIV, the Met-DM and GB-DM groups exhibited reduced IFN-α expression upon stimulation with whole- and split-virion influenza vaccines. Suppression of IFN-α expression in the Met-DM group was associated with a reduction in the mechanistic target of rapamycin complex-1 pathway and impaired IgG avidity index. Thus, single-dose TIV each year might not be suitable for T2DM. Our data could aid the development of an efficacious influenza vaccine for T2DM.
- Published
- 2020
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