Biology subjects

Wong, C. Y.

Publications and source records attributed to Wong, C. Y..

4 recordsLinked to original sources

bioRxiv2023

mRNA vaccines encoding membrane-anchored receptor-binding domains of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting

To address the limitations of whole-spike COVID vaccines, we explored mRNA vaccines encoding membrane-anchored receptor-binding domain (RBD-TMs), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail (CT) fragments of the SARS-CoV-2 spike protein. In naive mice, RBD-TM mRNA vaccines against ancestral SARS-CoV-2, Beta, Delta, Delta-plus, Kappa, Omicron BA.1 or BA.5, all induced strong humoral responses against the target RBD. Multiplex surrogate viral neutralization (sVNT) assays indicated broad neutralizing activity against a range of variant RBDs. In the setting of a heterologous boost, against the background of exposure to ancestral whole spike vaccines, sVNT studies suggested that RBD-TM vaccines were able to overcome the detrimental effects of immune imprinting. Omicron BA.1 and BA.5 RBD-TM booster vaccines induced serum antibodies with 12 and 22-fold higher neutralizing activity against the target RBD than their equivalent whole spike variants. Boosting with BA.1 or BA.5 RBD-TM provided good protection against more recent variants including XBB and XBB.1.5. Each RBD-TM mRNA is 28% of the length of its whole-spike equivalent. This advantage will enable tetravalent mRNA vaccines to be developed at well-tolerated doses of formulated mRNA. One Sentence SummarymRNA vaccines encoding membrane-anchored RBDs of SARS-CoV-2 mutants are effective vaccines that can overcome immune imprinting in mice

immunology↗

bioRxiv2021

Remotely sensed carotenoid dynamics predict photosynthetic phenology in conifer and deciduous forests

Crucially, the phenology of photosynthesis conveys the length of the growing season. Assessing the timing of photosynthetic phenology is key for terrestrial ecosystem models for constraining annual carbon uptake. However, model representation of photosynthetic phenology remains a major limitation. Recent advances in remote sensing allow detecting changes of foliar pigment composition that regulate photosynthetic activity. We used foliar pigments changes as proxies for light-use-efficiency (LUE) to model gross primary productivity (GPP) from remote sensing data. We evaluated the performance of LUE-models with GPP from eddy covariance and against MODerate Resolution Imaging Spectroradiometer (MODIS) GPP, a conventional LUE model, and a process-based dynamic global vegetation model at an evergreen needleleaf and a deciduous broadleaf forest. Overall, the LUE-models using foliar pigment information best captured the start and end of season, demonstrating that using regulatory carotenoids and photosynthetic efficiency in LUE models can improve remote monitoring of the phenology of forest vegetation.

plant biology↗

bioRxiv2020

High antibody titres induced by protein subunit vaccines against Buruli ulcer using Mycobacterium ulcerans antigens Hsp18 and MUL_3720

BackgroundMycobacterium ulcerans is the causative agent of a debilitating skin and soft tissue infection known as Buruli ulcer (BU). There is no vaccine against BU. The purpose of this study was to investigate the vaccine potential of two previously described immunogenic M. ulcerans proteins, MUL_3720 and Hsp18, using a mouse tail infection model of BU. MethodsRecombinant versions of the two proteins were each electrostatically coupled with a previously described lipopeptide adjuvant. Seven C57BL/6 and seven BALB/c mice were vaccinated and boosted with each of the formulations. Vaccinated mice were then challenged with M. ulcerans via subcutaneous tail inoculation. Vaccine performance was assessed by time-to-ulceration compared to unvaccinated mice. ResultsThe MUL_3720 and Hsp18 vaccines induced high titres of antigen-specific antibodies that were predominately subtype IgG1. However, all mice developed ulcers by day-40 post-M. ulcerans challenge. No significant difference was observed in the time-to-onset of ulceration between the experimental vaccine groups and unvaccinated animals. ConclusionsThese data align with previous vaccine experiments using Hsp18 and MUL_3720 that indicated these proteins may not be appropriate vaccine antigens. This work highlights the need to explore alternative vaccine targets and different approaches to understand the role antibodies might play in controlling BU.

microbiology↗

bioRxiv2019

Neuron-Glial Antigen 2 (NG2)-based Glial Induction ofHuman BMSCs: A fast & safe glial progenitor cell-based therapy for congenital myelin disorders of the central nervous system

ABSTRACT/ SUMMARYOligodendrocytes (OLs) are the only myelinating glia in the central nervous system (CNS). In congenital myelin disorders, OL dysfunction or death results in loss of myelin. This causes progressive and irreversible impairment to motor and cognitive functions, and is amongst the most disabling neurological disorder. Neonatal engraftment by glial progenitor cells (GPCs) allows the robust myelination of congenitally dysmyelinated brain, thereby preserving brain function and quality of life of patients. However, endogenous sources of glial progenitors are hard to obtain without causing secondary injury, while use of exogenous sources such as embryonic stem cells and induced-pluripotent stem cells face considerable ethical and safety issues. To circumvent such hurdles, we asked whether NG2+ cells in the bone marrow could be a potential cell source for GPCs. We successfully generated glial progenitor cells (GPCs) from human bone marrow stromal cells (hBMSCs) from 3 donors using a 14- day induction protocol. The generated hBMSC-GPCs were highly enriched in OPC marker expression, including OLIG2, PDGFR, NG2, SOX10 and O4, and showed efficient differentiation into myelinogenic oligodendrocytes when transplanted into postnatal day 7 (P7) myelin-deficient shiverer mice. Remyelination of the shiverer mouse brain significantly extended lifespan and improved motor function. The novel induction protocol described here provides a method for fast, simple and effective glial therapy for myelin disorders, overcoming existent hurdles of cell source restriction and time frame requirement. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=153 SRC="FIGDIR/small/658997v8_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@104a62corg.highwire.dtl.DTLVardef@399a67org.highwire.dtl.DTLVardef@1c81ee1org.highwire.dtl.DTLVardef@16374da_HPS_FORMAT_FIGEXP M_FIG C_FIG Highlights- Human bone marrow stromal cells (BMSCs) can be programmed to myelinating glia (GPCs, glial progenitor cells), via a novel 14-day in vitro induction protocol - Transplantation of these hBM-GPCs robustly remyelinated myelin deficient shiverer mice. - hBM-GPC transplant significantly extended lifespan, increased body weight and improved motor function

neuroscience↗