Despite tremendous progress in biomedical research and clinical care, emerging infectious diseases remain a threat to millions of people worldwide, causing thousands of deaths every day. The unpredictable and transient nature of outbreaks can result in massive disruption to livelihoods and cause global economic instability as we had witnessed with COVID-19, SARS and H1N1 outbreaks. A timely, efficient and coordinated response is required to save lives and limit the devastating consequences of epidemics. One of the key strategies for mitigating disease outbreaks is accelerating the pre-clinical and clinical development of vaccines and therapeutics that target infectious pathogens.
Vaccines are highly cost-effective public health tools. However, developing a safe and efficient vaccine is a long, costly and challenging process. By interfacing adaptive experimental and clinical trial design with detailed virological and immunological measurements, we have amassed a database of molecular correlates of vaccine safety and immunogenicity. Ongoing research to define molecular correlates that play a functional role in mediating desired vaccination outcome will further contribute to an evidence-based approach for prioritising key vaccine candidates for further clinical development.
Therapeutics such as antivirals and monoclonal antibodies are a crucial component of the medical arsenal against infectious diseases. Understanding the safety and mechanism of action for therapeutics early during clinical development will be beneficial to developing new drugs faster. This is particularly important for rapid outbreak response to emerging diseases of epidemic and pandemic potential.
Kalimuddin S, Tham CY, Qui M, de Alwis R, Sim JX, Lim JM, Tan HC, Syenina A, Zhang SL, Le Bert N, Tan AT, Leong YS, Yee JX, Ong EZ, Ooi EE, Bertoletti A, Low JG. Early T cell and binding antibody responses are associated with Covid-19 RNA vaccine efficacy onset. Med (N Y). 2021 Apr 8.
de Alwis R, Gan ES, Chen S, Leong YS, Tan HC, Zhang SL, Yau C, Low JGH, Kalimuddin S, Matsuda D, Allen EC, Hartman P, Park KJ, Alayyoubi M, Bhaskaran H, Dukanovic A, Bao Y, Clemente B, Vega J, Roberts S, Gonzalez JA, Sablad M, Yelin R, Taylor W, Tachikawa K, Parker S, Karmali P, Davis J, Sullivan BM, Sullivan SM, Hughes SG, Chivukula P, Ooi EE. A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice. Mol Ther. 2021 Jun 2;29(6):1970-1983.
Ong EZ, Kalimuddin S, Chia WC, Ooi SH, Koh CW, Tan HC, Zhang SL, Low JG, Ooi EE, Chan KR. Temporal dynamics of the host molecular responses underlying severe COVID-19 progression and disease resolution. EBioMedicine. 2021 Mar; 65:103262.
Low JG, Ng JHJ, Ong EZ, Kalimuddin S, Wijaya L, Chan YFZ, Ng DHL, Tan HC, Baglody A, Chionh YH, Lee DCP, Budigi Y, Sasisekharan R, Ooi EE (2020). Safety and efficacy of a therapeutic anti-yellow fever virus human antibody. N Engl J Med, 383:452-459.
Ong, E. Z., Chan, Y., Leong, W. Y., Lee, N., Kalimuddin, S., Haja Mohideen, S. M., Chan, K. S., Tan, A. T., Bertoletti, A., Ooi, E. E., & Low, J. (2020). A Dynamic Immune Response Shapes COVID-19 Progression. Cell host & microbe, S1931-3128(20)30185-2.
Chan KR, Gan ES, Chan CYY, Liang C, Low JZH, Zhang SL, Ong EZ, Bhatta A, Wijaya L, Lee YH, Low JG, Ooi EE. Metabolic perturbations and cellular stress underpin susceptibility to symptomatic live-attenuated yellow fever infection. Nat Med. 2019 Aug;25(8):1218-1224.
Ong EZ, Gan ES, de Alwis R, Wijaya L, Ong XM, Zhang M, Wong AW, Cheung YB, Zellweger RM, Ooi EE, Low JG. Genomic signature of early T-cell response is associated with lower antibody titer threshold for sterilizing immunity. Antiviral Res. 2019 Jun;166:35-41.
Kwek SS, Watanabe S, Chan KR, Ong EZ, Tan HC, Ng WC, Nguyen MTX, Gan ES, Zhang SL, Chan KWK, Tan JH, Sessions OM, Manuel M, Pompon J, Chua C, Hazirah S, Tryggvason K, Vasudevan SG, Ooi EE. A systematic approach to the development of a safe live attenuated Zika vaccine. Nat Commun. 2018 Mar 12;9(1):1031.
Tharakaraman K, Watanabe S, Chan KR, Huan J, Subramanian V, Chionh YH, Raguram A, Quinlan D, McBee M, Ong EZ, Gan ES, Tan HC, Tyagi A, Bhushan S, Lescar J, Vasudevan SG, Ooi EE, Sasisekharan R. Rational Engineering and Characterization of an mAb that Neutralizes Zika Virus by Targeting a Mutationally Constrained Quaternary Epitope. Cell Host Microbe. 2018 May 9;23(5):618-627.e6.
Chan CY, Chan KR, Chua CJ, Nur Hazirah S, Ghosh S, Ooi EE, Low JG. Early molecular correlates of adverse events following yellow fever vaccination. JCI Insight. 2017 Oct 5;2(19):e96031.
For more information on the terms of accreditation, click here.
