2023 |
Chia WN, Tan CW, Tan AWK, Young B, Starr TN, Lopez E, et al., 'Potent pan huACE2-dependent sarbecovirus neutralizing monoclonal antibodies isolated from a BNT162b2-vaccinated SARS survivor', Science Advances, 9 (2023) [C1]
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern such as Omicron hampered efforts in controlling the ongoing coronavirus disease 2... [more]
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern such as Omicron hampered efforts in controlling the ongoing coronavirus disease 2019 pandemic due to their ability to escape neutralizing antibodies induced by vaccination or prior infection, highlighting the need to develop broad-spectrum vaccines and therapeutics. Most human monoclonal antibodies (mAbs) reported to date have not demonstrated true pan-sarbecovirus neutralizing breadth especially against animal sarbecoviruses. Here, we report the isolation and characterization of highly potent mAbs targeting the receptor binding domain (RBD) of huACE2-dependent sarbecovirus from a SARS-CoV survivor vaccinated with BNT162b2. Among the six mAbs identified, one (E7) showed better huACE2-dependent sarbecovirus neutralizing potency and breadth than any other mAbs reported to date. Mutagenesis and cryo¿electron microscopy studies indicate that these mAbs have a unique RBD contact footprint and that E7 binds to a quaternary structure¿dependent epitope.
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2022 |
Marsh GA, McAuley AJ, Brown S, Pharo EA, Crameri S, Au GG, et al., 'In vitro characterisation of SARS-CoV-2 and susceptibility of domestic ferrets (Mustela putorius furo)', TRANSBOUNDARY AND EMERGING DISEASES, 69 297-307 (2022) [C1]
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2022 |
Karpe AV, Nguyen TV, Shah RM, Au GG, McAuley AJ, Marsh GA, et al., 'A Time-Series Metabolomic Analysis of SARS-CoV-2 Infection in a Ferret Model', Metabolites, 12 (2022) [C1]
The global threat of COVID-19 has led to an increased use of metabolomics to study SARS-CoV-2 infections in animals and humans. In spite of these efforts, however, understanding t... [more]
The global threat of COVID-19 has led to an increased use of metabolomics to study SARS-CoV-2 infections in animals and humans. In spite of these efforts, however, understanding the metabolome of SARS-CoV-2 during an infection remains difficult and incomplete. In this study, metabolic responses to a SAS-CoV-2 challenge experiment were studied in nasal washes collected from an asymptomatic ferret model (n = 20) at different time points before and after infection using an LC-MS-based metabolomics approach. A multivariate analysis of the nasal wash metabolome data revealed several statistically significant features. Despite no effects of sex or interaction between sex and time on the time course of SARS-CoV-2 infection, 16 metabolites were significantly different at all time points post-infection. Among these altered metabolites, the relative abundance of taurine was elevated post-infection, which could be an indication of hepatotoxicity, while the accumulation of sialic acids could indicate SARS-CoV-2 invasion. Enrichment analysis identified several pathways influenced by SARS-CoV-2 infection. Of these, sugar, glycan, and amino acid metabolisms were the key altered pathways in the upper respiratory channel during infection. These findings provide some new insights into the progression of SARS-CoV-2 infection in ferrets at the metabolic level, which could be useful for the development of early clinical diagnosis tools and new or repurposed drug therapies.
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2022 |
Au GG, Marsh GA, McAuley AJ, Lowther S, Trinidad L, Edwards S, et al., 'Characterisation and natural progression of SARS-CoV-2 infection in ferrets', Scientific Reports, 12 (2022) [C1]
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the infectious disease COVID-19, which has rapidly become an international pandemic with significan... [more]
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the infectious disease COVID-19, which has rapidly become an international pandemic with significant impact on healthcare systems and the global economy. To assist antiviral therapy and vaccine development efforts, we performed a natural history/time course study of SARS-CoV-2 infection in ferrets to characterise and assess the suitability of this animal model. Ten ferrets of each sex were challenged intranasally with 4.64 × 104 TCID50 of SARS-CoV-2 isolate Australia/VIC01/2020 and monitored for clinical disease signs, viral shedding, and tissues collected post-mortem for histopathological and virological assessment at set intervals. We found that SARS-CoV-2 replicated in the upper respiratory tract of ferrets with consistent viral shedding in nasal wash samples and oral swab samples up until day 9. Infectious SARS-CoV-2 was recovered from nasal washes, oral swabs, nasal turbinates, pharynx, and olfactory bulb samples within 3¿7¿days post-challenge; however, only viral RNA was detected by qRT-PCR in samples collected from the trachea, lung, and parts of the gastrointestinal tract. Viral antigen was seen exclusively in nasal epithelium and associated sloughed cells and draining lymph nodes upon immunohistochemical staining. Due to the absence of clinical signs after viral challenge, our ferret model is appropriate for studying asymptomatic SARS-CoV-2 infections and most suitable for use in vaccine efficacy studies.
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2021 |
Layton D, Burkett K, Marsh GA, Singanallur NB, Barr J, Layton R, et al., 'Type i Hypersensitivity in Ferrets Following Exposure to SARS-CoV-2 Inoculum: Lessons Learned', ILAR Journal, 62 232-237 (2021) [C1]
This case report discusses Type I hypersensitivity in ferrets following exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inoculum, observed during a study ... [more]
This case report discusses Type I hypersensitivity in ferrets following exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inoculum, observed during a study investigating the efficacy of candidate COVID-19 vaccines. Following a comprehensive internal root-cause investigation, it was hypothesized that prior prime-boost immunization of ferrets with a commercial canine C3 vaccine to protect against the canine distemper virus had resulted in primary immune response to fetal bovine serum (FBS) in the C3 preparation. Upon intranasal exposure to SARS-CoV-2 virus cultured in medium containing FBS, an allergic airway response occurred in 6 out of 56 of the ferrets. The 6 impacted ferrets were randomly dispersed across study groups, including different COVID-19 vaccine candidates, routes of vaccine candidate administration, and controls (placebo). The root-cause investigation and subsequent analysis determined that the allergic reaction was unrelated to the COVID-19 vaccine candidates under evaluation. Histological assessment suggested that the allergic response was characterized by eosinophilic airway disease; increased serum immunoglobulin levels reactive to FBS further suggested this response was caused by immune priming to FBS present in the C3 vaccine. This was further supported by in vivo studies demonstrating ferrets administered diluted FBS also presented clinical signs consistent with a hyperallergic response, while clinical signs were absent in ferrets that received a serum-free SARS-CoV-2 inoculum. It is therefore recommended that vaccine studies in higher order animals should consider the impact of welfare vaccination and use serum-free inoculum whenever possible.
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2021 |
Farr RJ, Rootes CL, Rowntree LC, Nguyen THO, Hensen L, Kedzierski L, et al., 'Altered microRNA expression in COVID-19 patients enables identification of SARS-CoV-2 infection', PLoS Pathogens, 17 (2021) [C1]
The host response to SARS-CoV-2 infection provide insights into both viral pathogenesis and patient management. The host-encoded microRNA (miRNA) response to SARS-CoV-2 infection,... [more]
The host response to SARS-CoV-2 infection provide insights into both viral pathogenesis and patient management. The host-encoded microRNA (miRNA) response to SARS-CoV-2 infection, however, remains poorly defined. Here we profiled circulating miRNAs from ten COVID-19 patients sampled longitudinally and ten age and gender matched healthy donors. We observed 55 miRNAs that were altered in COVID-19 patients during early-stage disease, with the inflammatory miR-31-5p the most strongly upregulated. Supervised machine learning analysis revealed that a three-miRNA signature (miR-423-5p, miR-23a-3p and miR-195-5p) independently classified COVID-19 cases with an accuracy of 99.9%. In a ferret COVID-19 model, the three-miRNA signature again detected SARS-CoV-2 infection with 99.7% accuracy, and distinguished SARS-CoV-2 infection from influenza A (H1N1) infection and healthy controls with 95% accuracy. Distinct miRNA profiles were also observed in COVID-19 patients requiring oxygenation. This study demonstrates that SARS-CoV-2 infection induces a robust host miRNA response that could improve COVID-19 detection and patient management.
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2021 |
Murray HC, Enjeti AK, Kahl RGS, Flanagan HM, Sillar J, Skerrett-Byrne DA, et al., 'Quantitative phosphoproteomics uncovers synergy between DNA-PK and FLT3 inhibitors in acute myeloid leukaemia', LEUKEMIA, 35 1782-1787 (2021)
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2021 |
Marsh GA, McAuley AJ, Au GG, Riddell S, Layton D, Singanallur NB, et al., 'ChAdOx1 nCoV-19 (AZD1222) vaccine candidate significantly reduces SARS-CoV-2 shedding in ferrets', NPJ VACCINES, 6 (2021) [C1]
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2021 |
Beale DJ, Shah R, Karpe A, Hillyer KE, McAuley AJ, Au GG, et al., 'Metabolic Profiling from an Asymptomatic Ferret Model of SARS-CoV-2 Infection', METABOLITES, 11 (2021) [C1]
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Nova |
2021 |
Harrison AR, Todd S, Dearnley M, David CT, Green D, Rawlinson SM, et al., 'Antagonism of STAT3 signalling by Ebola virus', PLOS PATHOGENS, 17 (2021) [C1]
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Nova |
2020 |
McAuley AJ, Kuiper MJ, Durr PA, Bruce MP, Barr J, Todd S, et al., 'Experimental and in silico evidence suggests vaccines are unlikely to be affected by D614G mutation in SARS-CoV-2 spike protein', npj Vaccines, 5 (2020) [C1]
The ¿D614G¿ mutation (Aspartate-to-Glycine change at position 614) of the SARS-CoV-2 spike protein has been speculated to adversely affect the efficacy of most vaccines and counte... [more]
The ¿D614G¿ mutation (Aspartate-to-Glycine change at position 614) of the SARS-CoV-2 spike protein has been speculated to adversely affect the efficacy of most vaccines and countermeasures that target this glycoprotein, necessitating frequent vaccine matching. Virus neutralisation assays were performed using sera from ferrets which received two doses of the INO-4800 COVID-19 vaccine, and Australian virus isolates (VIC01, SA01 and VIC31) which either possess or lack this mutation but are otherwise comparable. Through this approach, supported by biomolecular modelling of this mutation and the commonly-associated P314L mutation in the RNA-dependent RNA polymerase, we have shown that there is no experimental evidence to support this speculation. We additionally demonstrate that the putative elastase cleavage site introduced by the D614G mutation is unlikely to be accessible to proteases.
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2019 |
Annels NE, Mansfield D, Arif M, Ballesteros-Merino C, Simpson GR, Denyer M, et al., 'Phase I Trial of an ICAM-1-Targeted Immunotherapeutic-Coxsackievirus A21 (CVA21) as an Oncolytic Agent Against Non Muscle-Invasive Bladder Cancer', CLINICAL CANCER RESEARCH, 25 5818-5831 (2019)
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2018 |
Annels NE, Arif M, Simpson GR, Denyer M, Moller-Levet C, Mansfield D, et al., 'Oncolytic Immunotherapy for Bladder Cancer Using Coxsackie A21 Virus', MOLECULAR THERAPY-ONCOLYTICS, 9 1-12 (2018)
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2017 |
Sahoo SS, Quah MY, Nielsen S, Atkins J, Au GG, Cairns MJ, et al., 'Inhibition of extracellular matrix mediated TGF-ß signalling suppresses endometrial cancer metastasis.', Oncotarget, 8 (2017) [C1]
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Nova |
2016 |
Pandha HS, Annels N, Arif M, Mostafid H, Sandhu S, Harrington K, et al., 'Phase I/II CANON study: oncolytic immunotherapy for the treatment of non-muscle invasive bladder (NMIBC) cancer using intravesical coxsackievirus A21', Annals of Oncology, 27 vi361 (2016)
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2014 |
McIlroy DJ, Jarnicki AG, Au GG, Lott N, Smith DW, Hansbro PM, Balogh ZJ, 'Mitochondrial DNA neutrophil extracellular traps are formed after trauma and subsequent surgery', Journal of Critical Care, 29 1133.e1-1133.e5 (2014) [C1]
Introduction: Neutrophil extracellular traps (NETs) have not been demonstrated after trauma and subsequent surgery. Neutrophil extracellular traps are formed from pure mitochondri... [more]
Introduction: Neutrophil extracellular traps (NETs) have not been demonstrated after trauma and subsequent surgery. Neutrophil extracellular traps are formed from pure mitochondrial DNA (mtDNA) under certain conditions, which is potently proinflammatory. We hypothesized that injury and orthopedic trauma surgery would induce NET production with mtDNA as a structural component. Methods: Neutrophils were isolated 8 trauma patients requiring orthopedic surgery postinjury and up to 5 days postoperatively. Four healthy volunteers provided positive and negative controls. Total hip replacement patients acted as an uninjured surgical control group. Neutrophil extracellular traps were visualized with DNA (Hoechst 33342TM/Sytox Green/MitoSox/MitoTracker) stains using live cell fluorescence microscopy with downstream quantitative polymerase chain reaction analysis of DNA composition. Results: Neutrophil extracellular traps were present after injury in all 8 trauma patients. They persisted for 5 days postoperatively. Delayed surgery resulted in NET resolution, but they reformed postoperatively. Total hip replacement patients developed NETs postoperatively, which resolved by day 5. Quantitative polymerase chain reaction analysis of NET-DNA composition revealed that NETs formed after injury and surgery were made of mtDNA with no detectable nuclear DNA component. Conclusions: Neutrophil extracellular traps formed after major trauma and subsequent surgery contain mtDNA and represent a novel marker of heightened innate immune activation. They could be considered when timing surgery after trauma to prevent systemic NET-induced inflammatory complications.
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Nova |
2013 |
Kok CC, Au GG, 'Novel marker for recombination in the 3'-untranslated region of members of the species Human enterovirus A', ARCHIVES OF VIROLOGY, 158 765-773 (2013) [C1]
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Nova |
2011 |
Au GG, Beagley LG, Haley ES, Barry RD, Shafren DR, 'Oncolysis of malignant human melanoma tumors by Coxsackieviruses A13, A15 and A18', Virology Journal, 8 1-6 (2011) [C1]
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Nova |
2009 |
Haley ES, Au GG, Carlton BR, Barry RD, Shafren DR, 'Regional administration of oncolytic Echovirus 1 as a novel therapy for the peritoneal dissemination of gastric cancer', Journal of Molecular Medicine, 87 385-399 (2009) [C1]
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Nova |
2008 |
Howland LJ, Au GG, Barry RD, Shafren DR, 'Potent oncolytic activity of human enteroviruses against human prostate cancer', Prostate, 68 577-587 (2008) [C1]
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Nova |
2007 |
Au GG, Lincz L, Enno A, Shafren DR, 'Oncolytic Coxsackievirus A21 as a novel therapy for multiple myeloma', British Journal of Haematology, 137 133-141 (2007) [C1]
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2005 |
Au GG, Lindberg AM, Barry RD, Shafren DR, 'Oncolysis of vascular malignant human melanoma tumors by Coxsackievirus A21', International Journal of Oncology, 26 1471-1476 (2005) [C1]
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Nova |
2004 |
Hansbro NG, Johansson ES, Au GG, Lindberg A, Barry RD, Shafren DR, 'Enterovirus capsid interactions with decay-accelerating factor mediate lytic cell infection', Journal of Virology, 78 1431-1439 (2004) [C1]
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2004 |
Shafren DR, Au GG, Nguyen T, Barry RD, Hansbro NG, Harvey ES, et al., 'Systemic therapy of malignant human melanoma tumors by a common cold-producing enterovirus, Coxsackievirus A21', Clinical Cancer Research, 10 53-60 (2004) [C1]
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2003 |
Newcombe NG, Andersson P, Johansson ES, Au GG, Lindberg AM, Barry RD, Shafren DR, 'Cellular receptor interactions of C-cluster human group A coxsackieviruses', JOURNAL OF GENERAL VIROLOGY, 84 3041-3050 (2003)
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2000 |
Tooney PA, Au GG, Chahl LA, 'Localisation of tachykinin NK1 and NK3 receptors in the human prefrontal and visual cortex', Neuroscience Letters, 283 185-188 (2000) [C1]
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Nova |