MI2025 – Justin Chu

Title:
Next Generation Zika Virus Vaccine

Abstract:
The rise in global temperature, urbanisation, population growth, and migration have fuelled the magnitude and global distributions of mosquito-borne virus outbreak, namely from the flaviviruses which includes dengue virus (DENV), Zika virus (ZIKV), and West Nile virus (WNV). In particular, the recent ZIKV epidemic, resulted in occurrence of severe disease manifestations including congenital deformities and neurological disorders. Despite ZIKV outbreaks being sporadic currently, owing to the cyclic outbreak patterns of flaviviruses, future outbreaks with increased intensity can be expected. With no antiviral therapies available, vaccination remains as a key method to curb the spread of these mosquito-borne diseases. As opposed to previously published studies, in which live attenuated vaccine candidates (LAV) were developed through a chimeric construct or nucleotide deletion. Our approach utilises a large-scale recoding of the ZIKV genome, to which codons are replaced with non-synonymous mutations, as a proof-of-concept to generate a LAV that retains the native amino acid sequence. In addition, point mutation was inserted into the genome to improve attenuation and immunogenicity. We show that our LAV produces the in vitro attenuation phenotype such as reduction plaque sizes and replication kinetics in various cell lines. In our AG129 mice model, the LAV administered mice conferred a 100% sterilising protection against a lethal dose of wild-type ZIKV infection from a single dose of vaccination when compared to the control group.

Biography:
Dr Justin Jang Hann Chu is currently the Assistant Dean for Academic Affairs and an Associate Professor in the Department of Microbiology and Immunology and Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore He is holding a Joint Senior Principal Investigator in the Institute of Molecular and Cell Biology (IMCB), A*STAR. He is the Director of the Biosafety Level 3 Facility NUS. Justin is actively engaged in the study of the molecular virology of positive-sense RNA viruses of medical importance including SARS CoV-2, human enteroviruses that cause HFMD as well as mosquito-borne viruses including Dengue, Zika, West Nile and Chikungunya. The outcomes from these studies are helping to pave the roadmap towards the successful development antiviral strategies including vaccines and antiviral therapeutics. Fifteen patents and numerous scientific awards have been received from his current research. Justin has published over 150 international peer-reviewed scientific publications, six book chapters and over 200 conference papers. A number of these scientific papers are published in top-notch journals including Cell, Science, Lancet Infectious Diseases, Nature Immunology, Science Translational Medicine, Nature Communications, PNAS, EBiomedicine, PLoS Pathogens. A/P Chu is among the World’s Top 2% Scientists ranking published by Stanford University based on single-year data on citations received during the calendar year 2021, 2022 and 2023. He was the elected President of the Asia-Pacific Society of Medical Virology (2019-2024) and the current elected President of the Singapore Society for Microbiology and Biotechnology.