A5005005734- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- COVID-19 Clinical Research Studies
- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- Protein purification and stability
- SARS-CoV-2 detection and testing
- Computational Drug Discovery Methods
- Herpesvirus Infections and Treatments
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Animal Virus Infections Studies
- Poxvirus research and outbreaks
- PARP inhibition in cancer therapy
- Glycosylation and Glycoproteins Research
- Bacillus and Francisella bacterial research
- COVID-19 diagnosis using AI
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Viral-associated cancers and disorders
- Liver Disease Diagnosis and Treatment
- Complement system in diseases
- Influenza Virus Research Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Phenothiazines and Benzothiazines Synthesis and Activities
National Centre for Infectious Diseases
2022-2025
DSO National Laboratories
2013-2024
Tan Tock Seng Hospital
2023
National University of Singapore
2010-2015
ABSTRACT Mathematical models of viral dynamics are crucial in understanding infection trajectories. However, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) load data often includes limited sparse observations with significant heterogeneity. This study aims to: (1) understand the impact patient characteristics shaping temporal trajectory and (2) establish a collection protocol (DCP) to reliably reconstruct individual We collected longitudinal for SARS‐CoV‐2 Delta Omicron...
Although SARS-CoV-2-neutralizing antibodies are promising therapeutics against COVID-19, little is known about their mechanism(s) of action or effective dosing windows. We report the generation and development SC31, a potent SARS-CoV-2 neutralizing antibody, isolated from convalescent patient. Antibody-mediated neutralization occurs via an epitope within receptor-binding domain Spike protein. SC31 exhibited anti-SARS-CoV-2 activities in multiple animal models. In infected K18-human ACE2...
Tuberculosis (TB) is an airborne disease caused by Mycobacterium tuberculosis (Mtb). Whilst a functional role for humoral immunity in Mtb protection remains poorly defined, previous studies have suggested that antibodies can contribute towards host defense. Thus, identifying the critical components antibody repertoires from immune, chronically exposed, healthy individuals represents approach new determinants natural protection. In this study, we performed thorough analysis of IgG/IgA memory...
Abstract Introduction In August 2024, the World Health Organization (WHO) declared a public health emergency due to rapid spread of mpox in African and beyond. International travel controls (ITCs), such as screening viral testing, could help avoid/delay global monkeypox virus (MPXV), fostering preparedness response efforts. However, it is not clear whether tests at immigration are sufficient avoid importation MPXV which samples should be used on tests. Methods We conducted simulation study...
Abstract Antimicrobial resistance (AMR) is an emerging threat to global public health. Specifically, Acinetobacter baumannii ( A. ), one of the main pathogens driving rise nosocomial infections, a Gram-negative bacillus that displays intrinsic mechanisms and can also develop by acquiring AMR genes from other bacteria. More importantly, it resistant nearly 90% standard care (SOC) antimicrobial treatments, resulting in unsatisfactory clinical outcomes high infection-associated mortality rate...
Targeting model antigens (Ags) to Clec9A on DC has been shown induce, not only cytotoxic T cells, but also high levels of Ab. In fact, Ab responses against immunogenic Ag were effectively generated even in the absence DC-activating adjuvants. Here we tested if targeting weakly putative subunit vaccine Ags could enhance a level likely be protective. The proposed "universal" influenza Ag, M2e and enterovirus 71 SP70 linked anti-Clec9A Abs injected into mice. these greatly increased titres. For...
Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) led to multiple drug repurposing clinical trials that have yielded largely uncertain outcomes. To overcome this challenge, we used IDentif.AI, a platform pairs experimental validation with artificial intelligence (AI) and digital development rapidly pinpoint unpredictable interactions optimize infectious disease combination therapy design clinically relevant dosages. IDentif.AI was paired 12‐drug candidate...
IDentif.AI-x, a clinically actionable artificial intelligence platform, was used to rapidly pinpoint and prioritize optimal combination therapies against COVID-19 by pairing prospective, experimental validation of multi-drug efficacy on SARS-CoV-2 live virus Vero E6 assay with quadratic optimization workflow. A starting pool 12 candidate drugs developed in collaboration community infectious disease clinicians first narrowed down six-drug then interrogated 50 regimens at three dosing levels...
Abstract Our understanding of the conformational and electrostatic determinants that underlie targeting human leukocyte antigens (HLA) by anti-HLA alloantibodies is principally based upon in silico modelling. Here we provide a biochemical/biophysical functional characterization monoclonal alloantibody specific for common HLA type, HLA-A*11:01. We present 2.4 Å resolution map binding interface this antibody on HLA-A*11:01 compare structural with those utilized T-cell receptor (TCR),...
Abstract SARS-CoV-2-neutralizing antibodies are promising therapeutics for COVID-19. However, little is known about the mechanisms of action these or their effective dosing windows. We report discovery and development SC31, a potent SARS-CoV-2 neutralizing IgG1 antibody, originally isolated from convalescent patient at day 27 after onset symptoms. Neutralization occurs via binding epitope that maps within ACE2 interface Spike protein, conserved across all common circulating mutants. In...
Abstract The current clinical management of TB is complicated by the lack suitable diagnostic tests that can be employed in infrastructure and resource poor regions. mannose-capped form lipoarabinomannan (ManLAM) unique to surface envelope slow-growing, pathogenic mycobacteria such as M.tuberculosis (M.tb) facilitates passive invasion mononuclear phagocytes. detection this virulence factor urine, sputum serum has engendered interest its employment a biomarker for M.tb infection. In study, we...
Multi-polypeptide proteins such as antibodies are difficult to express in prokaryotic systems E. coli due the complexity of protein folding plus secretion. Thus far, proprietary strains or fermenter cultures have been required for appreciable yields. Previous studies shown that expression heterologous can be enhanced by reduction translation rates. In this paper, we demonstrate useful quantities full-length IgG expressed and purified from common laboratory strain HB2151 standard shaking...
Nanomedicine-based and unmodified drug interventions to address COVID-19 have evolved over the course of pandemic as more information is gleaned virus variants continue emerge. For example, some early therapies (e.g., antibodies) experienced markedly decreased efficacy. Due a growing concern future resistant variants, current development strategies are seeking find effective combinations. In this study, we used IDentif.AI, an artificial intelligence-derived platform, investigate drug–drug...
Tuberculosis is a major cause of mortality and morbidity due to infectious disease. However, current clinical diagnostic methodologies such as PCR, sputum culture, or smear microscopy are not ideal. Antibody-based assays suitable alternative but require specific antibodies against biomarker. Mycolic acid, which has been found in patient samples comprises large portion the mycobacterial cell wall, an ideal target. generating anti-lipid using traditional hybridoma challenging limited...
Epstein-Barr virus (EBV) is a common gammaherpesvirus associated with various human malignancies. Antibodies T cell receptor-like specificities (TCR-like mAbs) provide means to target intracellular tumor- or virus-associated antigens by recognising their processed peptides presented on major histocompatibility complex (MHC) class I (pMHC) complexes. These antibodies are however thought be relevant only for single HLA allele. Here, we show that HLA-A*02:01-restricted EBV antigenic...
Serological testing of Singaporeans who received childhood smallpox vaccination found anti-vaccinia IgG binding and neutralizing activity indicating long-term humoral immunity. There was correlation between titers could be used as a surrogate marker for In 2019, Singapore experienced case imported monkeypox. As with smallpox, disease can prevented through vaccination, which mandatory Singaporean infants until 1981. However, the degree residual immunity in older vaccinated remains unknown....
Anti-idiotype monoclonal antibodies represent a class of reagents that are potentially optimal for analyzing the pharmacokinetics fully human, anti-infective have been developed as therapeutic candidates. This is particularly important where direct pathogen binding assays complicated by requirements biosafety level III or IV handling. In this study, we describe development recombinant, anti-idiotype antibody termed E1 detection serotype-specific, candidate BSLIII Dengue virus 14c10 hG1. was...
Abstract Hepatitis B Virus (HBV) is a hepadnavirus that the principal pathogen underlying viral liver disease in human populations. In this study, we describe isolation and characterization of fully monoclonal antibody for HBV. This HuMab was isolated by combinatorial screen memory B-cell repertoire from an acute/recovered HBV-infected patient. Lead candidate selection based upon strong binding neutralizing activity live We provide detailed biochemical/biophysical, subclass its specificity...
The employment of monoclonal antibodies (Mabs) to identify disease-associated biomarkers in clinical samples represents the underlying principle for many diagnostic tests. To date, these have been principally developed protein targets with few reported applications lipids due their hydrophobicity and poor immunogenicity. Oxysterols represent a family implicated diverse human diseases where Mab-based detection assays could profound effect on utility as biomarkers. These are usually identified...
ABSTRACT The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and disease 2019 (COVID-19) has led to the rapid initiation urgently needed clinical trials repurposed drug combinations monotherapies. These regimens were primarily relying on mechanism-of-action based selection drugs, many which have yielded positive in vitro but largely negative outcomes. To overcome this challenge, we report use IDentif.AI, a platform that rapidly optimizes infectious (ID) combination...