Symposium 4

Prof Jenny Low

Senior Consultant

Department of Infectious Diseases

Singapore General Hospital

Dr Jenny Low is a senior consultant with the Department of Infectious Diseases in Singapore General Hospital and Professor at the Emerging Infectious Diseases Programme at Duke NUS Medical School. Concurrently, she is the co-director of the Viral Research and Experimental Medicine Centre@ SingHealth Duke-NUS (ViREMiCS) in the SingHealth Duke NUS AMC and deputy clinical and scientific director at the SingHealth Investigational Medicine Unit (IMU). Dr Low has been immersed in clinical research for more than 20 years. She has a long track record in conducting proof of concept and early phase clinical trials in acute viral diseases. She has tested several first-in-human therapeutics and biologics in humans including a therapeutic anti-yellow fever virus antibody Her current research focus is on early phase adaptive clinical trials of viral therapeutics and vaccine development as well as understanding the role of the early immune responses in modulating the outcome of infection or vaccination. She has been twice awarded the National Clinician Scientist Award in 2016 and 2019 for her research in host immune response to viral infections.

Session:

Beyond the Lab (Translational Efforts and Clinical Applications)
12 April 2024, 1315 - 1445, L1-S3

Presenting Title:

Metformin as Potential Drug to Biochemically Enhance Vaccine Immunogenicity in Type 2 Diabetes Mellitus

Vaccination is key to the control of several infectious diseases as emphatically demonstrated in the recent COVID-19 pandemic. Yet, vaccine response is not uniform across different subpopulations with people living with chronic diseases most impacted by poorer immune responses post vaccination. Type 2 DM is known to impair immune response to infections and vaccination even when their glycaemia control is optimal. One of the possibilities for this poorer response may be the immunomodulatory properties of the diabetic drug, metformin, that majority of T2DM patients are taking for their sugar control.

In a clinical study conducted on healthy volunteers who were pre-treated with metformin or placebo before they were administered the yellow fever (YF) live-attenuated vaccine, we found that when metformin was stopped at day 3 post vaccination, these individuals elicited higher YF neutralizing antibody levels compared to placebo-treated volunteers. Transcriptional and metabolomic analyses collectively showed that when metformin was stopped at Day 3, there was an expanded oxidative phosphorylation and protein translation capacities, which directly correlated with YF17D neutralizing antibody levels, without over-activation of cellular stress. Our findings suggest potential approaches to enhancing vaccine immunogenicity in T2DM.

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