Development of multi-epitope synthetic peptide vaccine against dengue virus Members: Kavita Reginald and Poh Chit Laa The dengue vaccine marketed by Sanofi Pasteur is only partially efficacious against two of the four serotypes of dengue virus (DENV). It is poorly efficacious against DENV serotypes 1 and 2, which are the main serotypes circulating in South East Asia. Data from different clinical trials indicate that a successful dengue vaccine must elicit both neutralising antibodies as well as cell mediated immunity. This can be achieved by designing multi-epitope peptide vaccines comprising CD4+, CD8+ and B-cell epitopes. While peptide vaccines are safe, biocompatible and cost effective, they are poorly immunogenic. The research project is focused on designing epitopes that are highly effective in eliciting protective CD8+-T cells against severe dengue and aids in the improvement of immunogenicity through research studies involving nanoparticles and adjuvants such as a squalene emulsion.
Development of antiviral peptides against dengue virus Members: Chew Miaw Fang and Poh Chit Laa There is an urgent need to develop antiviral drugs for the treatment of dengue as the long-term efficacy of commercial vaccine CYD-TDV against all four dengue virus serotypes remains unsatisfactory. Peptide was once a neglected choice of medical treatment but it has regained interest within the pharmaceutical industry. The research undertaken focuses on the design of novel peptidomimetics targeting the viral structural and no-structural proteins and the host cell receptors. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can translate into antiviral drugs for treating dengue.
Development of novel multiply mutated live attenuated vaccine strain against Enterovirus 71 Members: Isabel Yee Pinn Tsin and Poh Chit Laa Enterovirus 71 (EV-A71) is one of the leading pathogens of hand, foot and mouth disease (HFMD). It commonly causes mild symptoms such as fever and ulcers in children but some strains can produce cardiopulmonary odema which leads to death. There is no FDA-approved vaccine or antivirals against EV-A71 and the molecular determinants of virulence for EV-A71 remains unclear. Immunogenecity studies will confirm the specificity of the neutralising antibodies and the cellular immune responses while in vivo challenge studies with mouse-adapted EV-A71 will identify the protective immune markers.
microRNAs as potential therapeutics against dengue Virus Members: Wong Rui Rui, Siti Sarah Affendi and Poh Chit Laa Considering their critical roles in host-virus interactions, microRNAs (miRNAs) have been considered as ideal therapeutic targets for a number of viral infections. Understanding the miRNA expression and function during viral infections could provide insights into miRNA-based therapeutics, which could act as either miRNA antagonists or miRNA mimics. The known mechanisms of how miRNAs impact the dengue virus (DENV) replication are diverse; they could suppress the DENV multiplication by directly binding to the viral genome, resulting in translational repression or through modulation of the host innate immunity and suppression of interferon production. The research undertaken focuses on evaluating the efficacy of several miRNAs with known antiviral mechanisms against DENV in vitro and in vivo.