6 results on '"Oliver Carnell"'
Search Results
2. Syrian hamster convalescence from prototype SARS-CoV-2 confers measurable protection against the attenuated disease caused by the Omicron variant.
- Author
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Kathryn A Ryan, Kevin R Bewley, Robert J Watson, Christopher Burton, Oliver Carnell, Breeze E Cavell, Amy Challis, Naomi S Coombes, Elizabeth R Davies, Jack Edun-Huges, Kirsty Emery, Rachel Fell, Susan A Fotheringham, Karen E Gooch, Kathryn Gowan, Alastair Handley, Debbie J Harris, Richard Hesp, Laura Hunter, Richard Humphreys, Rachel Johnson, Chelsea Kennard, Daniel Knott, Sian Lister, Daniel Morley, Didier Ngabo, Karen L Osman, Jemma Paterson, Elizabeth J Penn, Steven T Pullan, Kevin S Richards, Sian Summers, Stephen R Thomas, Thomas Weldon, Nathan R Wiblin, Emma L Rayner, Richard T Vipond, Bassam Hallis, Francisco J Salguero, Simon G P Funnell, and Yper Hall
- Subjects
Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
The mutation profile of the SARS-CoV-2 Omicron (lineage BA.1) variant posed a concern for naturally acquired and vaccine-induced immunity. We investigated the ability of prior infection with an early SARS-CoV-2 ancestral isolate (Australia/VIC01/2020, VIC01) to protect against disease caused by BA.1. We established that BA.1 infection in naïve Syrian hamsters resulted in a less severe disease than a comparable dose of the ancestral virus, with fewer clinical signs including less weight loss. We present data to show that these clinical observations were almost absent in convalescent hamsters challenged with the same dose of BA.1 50 days after an initial infection with ancestral virus. These data provide evidence that convalescent immunity against ancestral SARS-CoV-2 is protective against BA.1 in the Syrian hamster model of infection. Comparison with published pre-clinical and clinical data supports consistency of the model and its predictive value for the outcome in humans. Further, the ability to detect protection against the less severe disease caused by BA.1 demonstrates continued value of the Syrian hamster model for evaluation of BA.1-specific countermeasures.
- Published
- 2023
- Full Text
- View/download PDF
3. A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19
- Author
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Jiandong Huo, Halina Mikolajek, Audrey Le Bas, Jordan J. Clark, Parul Sharma, Anja Kipar, Joshua Dormon, Chelsea Norman, Miriam Weckener, Daniel K. Clare, Peter J. Harrison, Julia A. Tree, Karen R. Buttigieg, Francisco J. Salguero, Robert Watson, Daniel Knott, Oliver Carnell, Didier Ngabo, Michael J. Elmore, Susan Fotheringham, Adam Harding, Lucile Moynié, Philip N. Ward, Maud Dumoux, Tessa Prince, Yper Hall, Julian A. Hiscox, Andrew Owen, William James, Miles W. Carroll, James P. Stewart, James H. Naismith, and Raymond J. Owens
- Subjects
Science - Abstract
Neutralizing nanobodies (Nb) are of considerable interest as therapeutic agents for COVID-19 treatment. Here, the authors functionally and structurally characterize Nbs that bind with high affinity to the receptor binding domain of the SARS-CoV-2 spike protein and show that an engineered homotrimeric Nb prevents disease progression in a Syrian hamster model of COVID-19 when administered intranasally.
- Published
- 2021
- Full Text
- View/download PDF
4. Development of a Hamster Natural Transmission Model of SARS-CoV-2 Infection
- Author
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Stuart Dowall, Francisco J. Salguero, Nathan Wiblin, Susan Fotheringham, Graham Hatch, Simon Parks, Kathryn Gowan, Debbie Harris, Oliver Carnell, Rachel Fell, Robert Watson, Victoria Graham, Karen Gooch, Yper Hall, Simon Mizen, and Roger Hewson
- Subjects
COVID-19 ,transmission ,animals ,Microbiology ,QR1-502 - Abstract
The global pandemic of coronavirus disease (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to an international thrust to study pathogenesis and evaluate interventions. Experimental infection of hamsters and the resulting respiratory disease is one of the preferred animal models since clinical signs of disease and virus shedding are similar to more severe cases of human COVID-19. The main route of challenge has been direct inoculation of the virus via the intranasal route. To resemble the natural infection, we designed a bespoke natural transmission cage system to assess whether recipient animals housed in physically separate adjacent cages could become infected from a challenged donor animal in a central cage, with equal airflow across the two side cages. To optimise viral shedding in the donor animals, a low and moderate challenge dose were compared after direct intranasal challenge, but similar viral shedding responses were observed and no discernible difference in kinetics. The results from our natural transmission set-up demonstrate that most recipient hamsters are infected within the system developed, with variation in the kinetics and levels of disease between individual animals. Common clinical outputs used for the assessment in directly-challenged hamsters, such as weight loss, are less obvious in hamsters who become infected from naturally acquiring the infection. The results demonstrate the utility of a natural transmission model for further work on assessing the differences between virus strains and evaluating interventions using a challenge system which more closely resembles human infection.
- Published
- 2021
- Full Text
- View/download PDF
5. A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19
- Author
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Robert J. Watson, Oliver Carnell, Jordan J. Clark, Francisco J. Salguero, Tessa Prince, William James, Michael J. Elmore, Miriam Weckener, Philip N. Ward, Audrey Le Bas, Chelsea Norman, Susan A. Fotheringham, Raymond J. Owens, Yper Hall, Parul Sharma, James H. Naismith, Adam Harding, Karen R. Buttigieg, Andrew Owen, Peter J. Harrison, Lucile Moynié, Jiandong Huo, Anja Kipar, Miles W. Carroll, Daniel K. Clare, James P. Stewart, Didier Ngabo, H. Mikolajek, Daniel Knott, Maud Dumoux, Joshua Dormon, Julia A. Tree, and Julian A. Hiscox
- Subjects
Male ,medicine.medical_treatment ,Science ,Mutant ,Intraperitoneal injection ,Dose-Response Relationship, Immunologic ,General Physics and Astronomy ,Hamster ,Alpha (ethology) ,Crystallography, X-Ray ,Article ,General Biochemistry, Genetics and Molecular Biology ,Epitope ,Epitopes ,Neutralization Tests ,medicine ,Antibody fragment therapy ,Animals ,Administration, Intranasal ,X-ray crystallography ,Multidisciplinary ,Mesocricetus ,biology ,SARS-CoV-2 ,Chemistry ,Cryoelectron Microscopy ,General Chemistry ,Single-Domain Antibodies ,biology.organism_classification ,Antibodies, Neutralizing ,Virology ,COVID-19 Drug Treatment ,Disease Models, Animal ,Spike Glycoprotein, Coronavirus ,biology.protein ,Female ,Antibody ,Golden hamster - Abstract
SARS-CoV-2 remains a global threat to human health particularly as escape mutants emerge. There is an unmet need for effective treatments against COVID-19 for which neutralizing single domain antibodies (nanobodies) have significant potential. Their small size and stability mean that nanobodies are compatible with respiratory administration. We report four nanobodies (C5, H3, C1, F2) engineered as homotrimers with pmolar affinity for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Crystal structures show C5 and H3 overlap the ACE2 epitope, whilst C1 and F2 bind to a different epitope. Cryo Electron Microscopy shows C5 binding results in an all down arrangement of the Spike protein. C1, H3 and C5 all neutralize the Victoria strain, and the highly transmissible Alpha (B.1.1.7 first identified in Kent, UK) strain and C1 also neutralizes the Beta (B.1.35, first identified in South Africa). Administration of C5-trimer via the respiratory route showed potent therapeutic efficacy in the Syrian hamster model of COVID-19 and separately, effective prophylaxis. The molecule was similarly potent by intraperitoneal injection., Neutralizing nanobodies (Nb) are of considerable interest as therapeutic agents for COVID-19 treatment. Here, the authors functionally and structurally characterize Nbs that bind with high affinity to the receptor binding domain of the SARS-CoV-2 spike protein and show that an engineered homotrimeric Nb prevents disease progression in a Syrian hamster model of COVID-19 when administered intranasally.
- Published
- 2021
6. Development of a Hamster Natural Transmission Model of SARS-CoV-2 Infection
- Author
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Graham J. Hatch, Simon Parks, Rachel Fell, Kathryn Gowan, Karen Gooch, Nathan Wiblin, Stuart Dowall, Robert J. Watson, Debbie Harris, Roger Hewson, Susan A. Fotheringham, Francisco J. Salguero, Yper Hall, Oliver Carnell, Victoria Graham, and Simon Mizen
- Subjects
Male ,Hamster ,Disease ,Biology ,medicine.disease_cause ,Microbiology ,Virus ,Article ,Pathogenesis ,Virology ,Cricetinae ,medicine ,Respiratory system ,Viral shedding ,Lung ,Coronavirus ,Mesocricetus ,Transmission (medicine) ,SARS-CoV-2 ,transmission ,COVID-19 ,Viral Load ,QR1-502 ,Virus Shedding ,animals ,Disease Models, Animal ,Infectious Diseases ,Female ,Nasal Cavity - Abstract
The global pandemic of coronavirus disease (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to an international thrust to study pathogenesis and evaluate interventions. Experimental infection of hamsters and the resulting respiratory disease is one of the preferred animal models since clinical signs of disease and virus shedding are similar to more severe cases of human COVID-19. The main route of challenge has been direct inoculation of the virus via the intranasal route. To resemble the natural infection, we designed a bespoke natural transmission cage system to assess whether recipient animals housed in physically separate adjacent cages could become infected from a challenged donor animal in a central cage, with equal airflow across the two side cages. To optimise viral shedding in the donor animals, a low and moderate challenge dose were compared after direct intranasal challenge, but similar viral shedding responses were observed and no discernible difference in kinetics. The results from our natural transmission set-up demonstrate that most recipient hamsters are infected within the system developed, with variation in the kinetics and levels of disease between individual animals. Common clinical outputs used for the assessment in directly-challenged hamsters, such as weight loss, are less obvious in hamsters who become infected from naturally acquiring the infection. The results demonstrate the utility of a natural transmission model for further work on assessing the differences between virus strains and evaluating interventions using a challenge system which more closely resembles human infection.
- Published
- 2021
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