Metformin-induced suppression of IFN-α via mTORC1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes

• Published in: Scientific reports Vol. 10; no. 1; pp. 3229 - 12
• Main Authors: Saenwongsa, Wipawee, Nithichanon, Arnone, Chittaganpitch, Malinee, Buayai, Kampaew, Kewcharoenwong, Chidchamai, Thumrongwilainet, Boonyarat, Butta, Patcharavadee, Palaga, Tanapat, Takahashi, Yoshimasa, Ato, Manabu, Lertmemongkolchai, Ganjana
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.02.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/21; 13/95; 38; 38/77; 631/250/590; 692/700/459/1748; Aged; Antibodies, Viral - immunology; Antibody Affinity - immunology; Antibody Formation - drug effects; Antibody response; Antidiabetics; Antigens; Avidity; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - immunology; Female; Glibenclamide; Glyburide - pharmacology; Glyburide - therapeutic use; Hemagglutination inhibition; Hemagglutination Inhibition Tests; Humanities and Social Sciences; Humans; Immunization; Immunoglobulin G; Immunoglobulin G - metabolism; Influenza; 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; Influenza B virus - drug effects; Influenza B virus - immunology; Influenza Vaccines - immunology; Interferon-alpha - pharmacology; Male; Mechanistic Target of Rapamycin Complex 1 - metabolism; Metformin; Metformin - pharmacology; Metformin - therapeutic use; Monocytes - drug effects; Monocytes - metabolism; multidisciplinary; Rapamycin; Science; Science (multidisciplinary); Seasons; Signal transduction; Signal Transduction - drug effects; TOR protein; Vaccination; Vaccines; Virion - drug effects; Virion - immunology; Virions; α-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-60213-0

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.