Ganjana Lertmemongkolchai 2019

Dr Ganjana Lertmemongkolchai

Khon Kaen University, Thailand

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

Poster Abstract

Diabetes mellitus (DM) patients are at an increased risk of complications following influenza-virus infection, so seasonal vaccination is recommended. However, seasonal vaccination 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 DM following seasonal vaccination, and examined the effects of 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 group. DM impaired the IgG Avidity Index, and DM groups treated with metformin (Met-DM) or glibenclamide (GB-DM) showed a low response against H1N1, in addition to delaying and reducing haemagglutination-inhibition persistency against influenza B-antigens. Following TIV, Met-DM and GB-DM groups showed 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 DM. Our data could aid development of an efficacious influenza vaccine for DM individuals.

Biography

Dr Ganjana Lertmemongkolchai has spent the last 20 years working on neglected tropical diseases, specifically melioidosis and more broadly sepsis and diabetes mellitus. Her core expertise is in cellular immunology, and her laboratory at Khon Kaen University in Thailand, underpins major collaborative studies in human cellular immunology, host-pathogen interaction and biomarker research with biosafety containment level 3 facilities registered with CDC, USA since 2005.

In long term collaboration with Prof Gregory Bancroft at London School of Hygiene and Tropical Medicine and Dr Manabu Ato at National Institute of Infectious Diseases in Tokyo, her laboratory has studied human cellular functions in response to Burkholderia pseudomallei, particularly pro-inflammatory cytokines and neutrophils in the context of diabetes mellitus leading to host susceptibility to the infection. In addition, human T cell epitopes to B. pseudomallei were studied in collaboration with Prof Danny Altmann at Imperial College London and human functional B and T cell epitopes were analyzed as predicted by structure and sequence based techniques in collaborations with Prof Martino Bolognesi and Dr Louise Gourlay at Department of Biosciences, University of Milano, Prof Giorgio Colombo at Istituto di Chimica del Riconoscimento Molecolare, and University of Pavia in Milan, Italy and Prof Xavier Daura at Autonomous University of Barcelona in Spain.