A5100726077- Mosquito-borne diseases and control
- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Vectors
- COVID-19 Clinical Research Studies
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- Immune Cell Function and Interaction
- Viral Infections and Outbreaks Research
- T-cell and B-cell Immunology
- Virus-based gene therapy research
- interferon and immune responses
- Spectroscopy Techniques in Biomedical and Chemical Research
- Nonmelanoma Skin Cancer Studies
- Virology and Viral Diseases
- Protease and Inhibitor Mechanisms
- vaccines and immunoinformatics approaches
- Insect symbiosis and bacterial influences
- SARS-CoV-2 detection and testing
- Wound Healing and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Immune Response and Inflammation
- Blood properties and coagulation
- Lung Cancer Research Studies
- Dermatology and Skin Diseases
- Autoimmune and Inflammatory Disorders Research
QIMR Berghofer Medical Research Institute
2016-2025
University of Transport and Communications
2023
Osaka City University
2021
University of Labor and Social Affairs
2020
Christiana Care Health System
2018
National Institute of Animal Sciences
2016
Australian e-Health Research Centre
2014
Florida Keys Community College
2013
Griffith University
2011
The University of Melbourne
2004
ABSTRACT Chikungunya virus is a mosquito-borne arthrogenic alphavirus that has recently reemerged to produce the largest epidemic ever documented for this virus. Here we describe new adult wild-type mouse model of chikungunya arthritis, which recapitulates self-limiting tenosynovitis, and myositis seen in humans. Rheumatic disease was associated with prolific infiltrate monocytes, macrophages, NK cells production monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha...
Abstract The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We demonstrate that despite large size of viral RNA genome (~30 kb), infectious full-length cDNA readily assembled in vitro a circular polymerase extension reaction (CPER) methodology without need for technically demanding intermediate steps. Overlapping fragments are generated from and together with linker fragment containing CMV promoter into single reaction. Transfection...
Heparan sulfate (HS) is a cell surface polysaccharide recently identified as coreceptor with the ACE2 protein for S1 spike on SARS-CoV-2 virus, providing tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have anticoagulant and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), cancer drug candidate, binds destabilizes receptor binding domain directly inhibits its to ACE2,...
Options for skin cancer treatment currently include surgery, radiotherapy, topical chemotherapy, cryosurgery, curettage, and electrodessication. Although effective, surgery is costly unsuitable certain patients. Radiotherapy can leave a poor cosmetic effect, current chemotherapy limited by low cure rates extended schedules. Here, we describe the preclinical activity of novel chemotherapeutic agent cancer, 3-ingenyl angelate (PEP005), hydrophobic diterpene ester isolated from plant Euphorbia...
A simple generic peptide-based vaccine structure that targets Toll-like receptor 2-expressing dendritic cells and causes their activation is described. The vaccines are totally synthetic, serve as own adjuvant, composed of ( i ) a single helper T cell epitope, ii target epitope either recognized by CD8 + or B cells, iii 2-targeting lipid moiety, S -[2,3-bis(palmitoyloxy)propyl]cysteine, situated between the peptide epitopes to form branched configuration. different examined were from...
ABSTRACT Chikungunya virus (CHIKV) infections can produce severe disease and mortality. Here we show that CHIKV infection of adult mice deficient in interferon response factors 3 7 (IRF3/7 −/− ) is lethal. Mortality was associated with undetectable levels alpha/beta (IFN-α/β) serum, ∼50- ∼10-fold increases IFN-γ tumor necrosis factor (TNF), respectively, increased replication, edema, vasculitis, hemorrhage, fever followed by hypothermia, oliguria, thrombocytopenia, raised hematocrits. These...
Heat shock protein 10 (Hsp10) and heat 60 (Hsp60) were originally described as essential mitochondrial proteins involved in folding. However, both have also been shown to a number of extracellular immunomodulatory activities. Here we show that purified recombinant human Hsp10 incubated with cells vitro reduced lipopolysaccharide (LPS)-induced nuclear factor-κB activation secretion several inflammatory mediators from RAW264.7 cells, murine macrophages, peripheral blood mononuclear cells....
The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV) has prompted a quest to understand correlates protection against and disease in order inform development new interventions. Herein we highlight propensity CHIKV infections persist long term, both as persistent, steady-state, viraemias multiple B cell deficient mouse strains, persistent RNA (including negative-strand RNA) wild-type mice. knockout studies provided evidence for role T cells (but not NK cells)...
Abstract Harnessing neutrophils for the eradication of cancer cells remains an attractive but still controversial notion. In this study, we provide evidence that are required to prevent relapse skin tumors following topical treatment with a new anticancer agent, ingenol-3-angelate (PEP005). Topical PEP005 induces primary necrosis tumor cells, potently activates protein kinase C, and was associated acute T cell-independent inflammatory response characterized by pronounced neutrophil...
The emerging arthritogenic, mosquito-borne chikungunya virus (CHIKV) causes severe disease in humans and represents a serious public health threat countries where Aedes spp mosquitoes are present. This study describes for the first time successful production of CHIKV virus-like particles (VLPs) insect cells using recombinant baculoviruses. well-established expression system is rapidly scalable to volumes required epidemic responses proved well suited processing glycoproteins enveloped VLPs....
Chikungunya virus (CHIKV) is a member of globally distributed group arthritogenic alphaviruses that cause weeks to months debilitating polyarthritis/arthralgia, which often poorly managed with current treatments. Arthritic disease usually characterized by high levels the chemokine CCL2 and prodigious monocyte/macrophage infiltrate. Several inhibitors its receptor CCR2 are in development may find application for treatment certain inflammatory conditions, including autoimmune viral...
Chikungunya virus (CHIKV) is an arthritogenic alphavirus causing epidemics of acute and chronic arthritic disease. Herein we describe a comprehensive RNA-Seq analysis feet lymph nodes at peak viraemia (day 2 post infection), arthritis 7) disease 30) in the CHIKV adult wild-type mouse model. Genes previously shown to be up-regulated patients were also sequence information was obtained with up ≈8% reads mapping viral genome; however, no adaptive genome changes apparent. Although day 2, 7 30...
Abstract Zika and chikungunya viruses have caused major epidemics are transmitted by Aedes aegypti and/or albopictu s mosquitoes. The “Sementis Copenhagen Vector” (SCV) system is a recently developed vaccinia-based, multiplication-defective, vaccine vector technology that allows manufacture in modified CHO cells. Herein we describe single-vector construct SCV encodes the structural polyprotein cassettes of both from different loci. A single vaccination mice induces neutralizing antibodies to...
ABSTRACT A single blind, randomized, placebo-controlled, single-center phase I clinical trial of a CD8 + T-cell peptide epitope vaccine against infectious mononucleosis was conducted with 14 HLA B*0801-positive, Epstein-Barr virus (EBV)-seronegative adults. The comprised the B*0801-restricted FLRGRAYGL and tetanus toxoid formulated in water-in-oil adjuvant, Montanide ISA 720. FLRGRAYGL-specific responses were detected 8/9 peptide-vaccine recipients 0/4 placebo by gamma interferon...
Abstract SerpinB2 (plasminogen activator inhibitor-2) is widely described as an inhibitor of urokinase plasminogen activator; however, SerpinB2−/− mice show no detectable increase in activity. In this study, we describe unexpected immune phenotype mice. After immunization with OVA CFA, made ≈6-fold more IgG2c and generated ≈2.5-fold OVA-specific IFN-γ–secreting T cells than SerpinB2+/+ littermate controls. mice, high inducible expression was seen at the injection site macrophages low levels...
Human
Chikungunya virus (CHIKV) belongs to a group of mosquito-borne alphaviruses associated with acute and chronic arthropathy, peripheral limb joints most commonly affected. Using mouse model CHIKV infection arthritic disease, we show that replication the ensuing foot arthropathy were dramatically reduced when mice housed at 30°C, rather than conventional 22°C. The effect was not detectable fever, but dependent on type I interferon responses. Bioinformatics analyses RNA-Seq data after injection...
Chikungunya virus (CHIKV), Ross River (RRV), o'nyong nyong (ONNV), Mayaro (MAYV) and Getah (GETV) represent arthritogenic alphaviruses belonging to the Semliki Forest antigenic complex. Antibodies raised against one of these viruses can cross-react with other serogroup members, suggesting that, for instance, a CHIKV vaccine (deemed commercially viable) might provide cross-protection antigenically related alphaviruses. Herein we use human alphavirus isolates (including new RRV isolate)...
SARS-CoV-2 uses the human ACE2 (hACE2) receptor for cell attachment and entry, with mouse (mACE2) unable to support infection. Herein we describe an ACE2-lentivirus system illustrate its utility in vitro vivo infection models. Transduction of non-permissive lines hACE2 imparted replication competence, transduction mACE2 containing N30D, N31K, F83Y H353K substitutions, match hACE2, rescued replication. Intrapulmonary hACE2-lentivirus C57BL/6J mice permitted significant virus lung epithelium....
The international SARS-CoV-2 pandemic has resulted in an urgent need to identify new anti-viral drugs for treatment of COVID-19. initial step identifying potential candidates usually involves vitro screening that includes standard cytotoxicity controls. Under-appreciated is viable, but stressed or otherwise compromised cells, can also have a reduced capacity replicate virus. A refinement proposed herein drug thus simple growth assay concentrations cause cellular stress "cytomorbidity", as...
Vaccines pave the way out of SARS-CoV-2 pandemic. Besides mRNA and adenoviral vector vaccines, effective protein-based vaccines are needed for immunization against current emerging variants. We have developed a virus-like particle (VLP)-based vaccine using baculovirus-insect cell expression system, robust production platform known its scalability, low cost, safety. Baculoviruses were constructed encoding spike proteins: full-length S, stabilized secreted or S1 domain. Since subunit S only...
How well mouse models recapitulate the transcriptional profiles seen in humans remains debatable, with both conservation and diversity identified various settings. Herein we use RNA-Seq data bioinformatics approaches to analyze responses SARS-CoV-2 infected lungs, comparing 4 human studies widely used K18-hACE2 model, a model where hACE2 is expressed from ACE2 promoter, that uses adapted virus wild-type mice. Overlap of single copy orthologue differentially genes (scoDEGs) between was...
Fourier transform infrared (FTIR) spectroscopy provides a (bio)chemical snapshot of the sample, and was recently used in proof-of-concept cohort studies for COVID-19 saliva screening. However, biological basis proposed technology has not been established. To investigate underlying pathophysiology, we conducted controlled infection experiments on Vero E6 cells vitro K18-hACE2 mice vivo. Potentially infectious culture supernatant or mouse oral lavage samples were treated with ethanol 75% (v/v)...