Utilising proteomics to develop anti-HCMV immunotherapy
Lead Research Organisation:
CARDIFF UNIVERSITY
Department Name: School of Medicine
Abstract
Human cytomegalovirus (HCMV) is a herpesvirus that infects almost everyone worldwide. Infection is lifelong, during which time it is controlled by the immune system. While the majority of infections do not cause symptoms, HCMV is nevertheless a major cause of disease in certain groups of people. If caught during pregnancy, the virus can pass to the foetus and can result in deafness, mental retardation, or even death of the unborn child. In the UK up to 1000 babies per year have severe permanent disabilities due to HCMV, more than Down's syndrome or foetal alcohol syndrome. HCMV is a major cause of severe life-threatening disease in individuals with poor immune systems, notably transplant patients and people with HIV/AIDs. HCMV has also been associated with the most common form of brain cancer, hardening of the arteries, premature aging of the immune system, hepatitis and inflammatory bowel problems. Antiviral drugs have toxic side effects, and viruses rapidly become resistant to them. There is an urgent need for better therapeutic options.
CMV is the most complex human virus. Unfortunately we, and others, have shown that the virus changes whenever it is grown in the laboratory. This means that researchers have not been able to study the actual virus that causes clinical disease, and this has limited the development of vaccines and therapy. To solve this problem we took a clinical virus, sequenced its genome and designated it strain Merlin. This has been adopted as the worldwide HCMV reference strain. My work has characterised how this virus changes when grown in the lab and enabled me to devise a unique system to stop these changes happening. For the first time, scientists can perform experiments with a virus that accurately mimics the virus that causes disease. I will now use this virus, along with state-of-the-art technology, to define all HCMV proteins that can be targeted for vaccination or therapy.
To date vaccines have aimed to prevent initial infection with the virus. These studies need to target proteins present in the virus, yet the entire set of proteins present in clinical virus is completely unknown. Using our viruses we can now define the complete set of proteins available for targeting.
Although these vaccine strategies may reduce the chances of becoming infected, they cannot stop infection completely. Once a person is infected, a different strategy is required - one that enables cells to be killed after they are infected. The immune system can only kill infected cells if it can recognise them, yet we don't know how the virus changes infected cells. Using our state-of-the-art techniques and viruses, we will now determine exactly how HCMV changes the surface of an infected cell. We will determine which of these changes are the best targets for killing infected cells, and engineer antibodies that can be given to patients to enable their immune system to recognise these cells, and kill them - thereby controlling the HCMV infection.
Although we are in a unique position to develop and test these therapeutic reagents against infected cells, our novel viruses still suffer from a limitation. Virus is naturally spread by being secreted in bodily fluids (e.g. urine, saliva). To understand and control the process by which the virus spreads between people, we must be able to mimic this process in the lab. Yet when we grow clinical virus in the lab, very little virus is secreted. We have shown that this is because of a viral gene called RL13. We will investigate how RL13 stops secretion of virus, how this can be circumvented in the lab, and how it is circumvented when virus is secreted in patients. This will enable the production of large amounts of secreted virus that, as closely as possible, represents virus secreted from patients. This is crucial to enable laboratories to investigate the way HCMV spreads between people, and to develop ways of stopping it happening.
CMV is the most complex human virus. Unfortunately we, and others, have shown that the virus changes whenever it is grown in the laboratory. This means that researchers have not been able to study the actual virus that causes clinical disease, and this has limited the development of vaccines and therapy. To solve this problem we took a clinical virus, sequenced its genome and designated it strain Merlin. This has been adopted as the worldwide HCMV reference strain. My work has characterised how this virus changes when grown in the lab and enabled me to devise a unique system to stop these changes happening. For the first time, scientists can perform experiments with a virus that accurately mimics the virus that causes disease. I will now use this virus, along with state-of-the-art technology, to define all HCMV proteins that can be targeted for vaccination or therapy.
To date vaccines have aimed to prevent initial infection with the virus. These studies need to target proteins present in the virus, yet the entire set of proteins present in clinical virus is completely unknown. Using our viruses we can now define the complete set of proteins available for targeting.
Although these vaccine strategies may reduce the chances of becoming infected, they cannot stop infection completely. Once a person is infected, a different strategy is required - one that enables cells to be killed after they are infected. The immune system can only kill infected cells if it can recognise them, yet we don't know how the virus changes infected cells. Using our state-of-the-art techniques and viruses, we will now determine exactly how HCMV changes the surface of an infected cell. We will determine which of these changes are the best targets for killing infected cells, and engineer antibodies that can be given to patients to enable their immune system to recognise these cells, and kill them - thereby controlling the HCMV infection.
Although we are in a unique position to develop and test these therapeutic reagents against infected cells, our novel viruses still suffer from a limitation. Virus is naturally spread by being secreted in bodily fluids (e.g. urine, saliva). To understand and control the process by which the virus spreads between people, we must be able to mimic this process in the lab. Yet when we grow clinical virus in the lab, very little virus is secreted. We have shown that this is because of a viral gene called RL13. We will investigate how RL13 stops secretion of virus, how this can be circumvented in the lab, and how it is circumvented when virus is secreted in patients. This will enable the production of large amounts of secreted virus that, as closely as possible, represents virus secreted from patients. This is crucial to enable laboratories to investigate the way HCMV spreads between people, and to develop ways of stopping it happening.
Technical Summary
Development of vaccines and therapy requires that research uses viruses that mimic the agent of disease. We have developed the only HCMV BAC containing a complete wildtype genome, and can prevent in-vitro mutation by tet-repressing the unstable regions UL128L and RL13, enabling growth of high titre, genetically wildtype virus. During subsequent infection without repression, the entire virion proteome is expressed for analysis. We will use this virus to define and validate the entire proteome available for therapeutic targeting.
For the production of neutralising antibodies and inhibitors of viral entry, the virion proteome of wildtype virus will be defined. These strategies can reduce transmission, but spread in vivo is cell-to-cell, for which antibody dependent cellular cytotoxicity (ADCC) antibodies may be more effective. We will use Stable Isotope Labelling of Amino Acids in Cell Culture (SILAC) of surface proteins to define all potential targets for ADCC antibodies on the infected cell. We will determine which are targets during natural infection, and the functional consequences of viral encoded Fc binding proteins in circumventing ADCC. We will engineer chimeric antibodies against targets, and test their ability to promote ADCC killing of infected cells for therapy.
Our viruses permit the study of wildtype HCMV infected cells, but it remains hard to produce high titre cell free wildtype virus for studying virus entry, because RL13 (an Fc binding protein) inhibits virus release. We have defined the binding partners of RL13 using SILAC-IP and will determine, and circumvent, the interactions responsible for this inhibition. This will enable the production of high titre wildtype virus (with reference to our virion proteome). Since RL13 inhibits virus release, we will determine whether clinical virus lacks gpRL13 when secreted at high titres into urine. Finally we will begin determining whether RL13 promotes persistence of Rhesus CMV based vaccine vectors.
For the production of neutralising antibodies and inhibitors of viral entry, the virion proteome of wildtype virus will be defined. These strategies can reduce transmission, but spread in vivo is cell-to-cell, for which antibody dependent cellular cytotoxicity (ADCC) antibodies may be more effective. We will use Stable Isotope Labelling of Amino Acids in Cell Culture (SILAC) of surface proteins to define all potential targets for ADCC antibodies on the infected cell. We will determine which are targets during natural infection, and the functional consequences of viral encoded Fc binding proteins in circumventing ADCC. We will engineer chimeric antibodies against targets, and test their ability to promote ADCC killing of infected cells for therapy.
Our viruses permit the study of wildtype HCMV infected cells, but it remains hard to produce high titre cell free wildtype virus for studying virus entry, because RL13 (an Fc binding protein) inhibits virus release. We have defined the binding partners of RL13 using SILAC-IP and will determine, and circumvent, the interactions responsible for this inhibition. This will enable the production of high titre wildtype virus (with reference to our virion proteome). Since RL13 inhibits virus release, we will determine whether clinical virus lacks gpRL13 when secreted at high titres into urine. Finally we will begin determining whether RL13 promotes persistence of Rhesus CMV based vaccine vectors.
Planned Impact
Successfully preventing HCMV disease has huge health and financial implications - other than genetic defects, HCMV accounts for more cases of congenital malformation and deafness than any other, and in the USA, the lifelong costs associated with congenital HCMV infection is estimated to be around $4 billion per year. It is clear that work leading to treatment or vaccination is of major importance and will see benefits worldwide.
Our development of a clonal, wildtype HCMV genome, has already had clear benefit to companies developing diagnostics for HCMV, with Merlin being designated the first international diagnostic standard for HCMV. The BAC clone is also being used for drug discovery in the field of peptide based drugs and virus derived from the BAC is also being used as a vaccine vector to vaccinate against TB. However these vaccine vectors have, to date, had to lack important components of the virion envelope, potentially compromising their effectiveness. The work in the project will enable us to produce the first clonal virus that stably expresses the complete wildtype HCMV proteome. This virus will be the definitive virus with which to test and develop diagnostics and therapeutics. Companies that are using HCMV as a vaccine delivery agent will also benefit from the development of wildtype virus, and the knowledge of whether and which tropism modifiers in the genome of a vaccine strain are beneficial in terms of attenuating virus while stimulating an immune response.
Using wildtype virus to define the complete set of therapeutic targets available within the virion itself, or on the surface of the infected cell, and developing chimeric antibodies to take advantage of this information, has the potential to completely change the landscape of HCMV therapy. Chimeric antibodies will offer the chance to readily control HCMV in vivo, and this work will define which proteins within the virus are ideal for targeting in a vaccine. Together these advances will bring health and financial benefits to both patients and the pharmaceutical industry.
Under all of these scenarios, the companies involved will benefit from the use of the reagents, technologies and principles developed in this grant. The staff member employed on the grant will obtain expertise in a wide range of scientific techniques, including molecular biology, proteomics, virology and immunology. They will obtain experience of presenting at both national and international meetings, and writing scientific papers. Through the development of chimeric antibodies, they will also work with our research and commercial division (RACD) to ensure we have patent protection for any reagents we successfully produce. Thus they will obtain a wide range of skills that can be applied in multiple job sectors.
Our development of a clonal, wildtype HCMV genome, has already had clear benefit to companies developing diagnostics for HCMV, with Merlin being designated the first international diagnostic standard for HCMV. The BAC clone is also being used for drug discovery in the field of peptide based drugs and virus derived from the BAC is also being used as a vaccine vector to vaccinate against TB. However these vaccine vectors have, to date, had to lack important components of the virion envelope, potentially compromising their effectiveness. The work in the project will enable us to produce the first clonal virus that stably expresses the complete wildtype HCMV proteome. This virus will be the definitive virus with which to test and develop diagnostics and therapeutics. Companies that are using HCMV as a vaccine delivery agent will also benefit from the development of wildtype virus, and the knowledge of whether and which tropism modifiers in the genome of a vaccine strain are beneficial in terms of attenuating virus while stimulating an immune response.
Using wildtype virus to define the complete set of therapeutic targets available within the virion itself, or on the surface of the infected cell, and developing chimeric antibodies to take advantage of this information, has the potential to completely change the landscape of HCMV therapy. Chimeric antibodies will offer the chance to readily control HCMV in vivo, and this work will define which proteins within the virus are ideal for targeting in a vaccine. Together these advances will bring health and financial benefits to both patients and the pharmaceutical industry.
Under all of these scenarios, the companies involved will benefit from the use of the reagents, technologies and principles developed in this grant. The staff member employed on the grant will obtain expertise in a wide range of scientific techniques, including molecular biology, proteomics, virology and immunology. They will obtain experience of presenting at both national and international meetings, and writing scientific papers. Through the development of chimeric antibodies, they will also work with our research and commercial division (RACD) to ensure we have patent protection for any reagents we successfully produce. Thus they will obtain a wide range of skills that can be applied in multiple job sectors.
Organisations
Publications
Assaifan AK
(2016)
Nanotextured Surface on Flexographic Printed ZnO Thin Films for Low-Cost Non-Faradaic Biosensors.
in ACS applied materials & interfaces
Elasifer H
(2020)
Downregulation of HLA-I by the molluscum contagiosum virus mc080 impacts NK-cell recognition and promotes CD8+ T-cell evasion.
in The Journal of general virology
Fielding CA
(2014)
Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation.
in PLoS pathogens
Fletcher-Etherington A
(2020)
Human cytomegalovirus protein pUL36: A dual cell death pathway inhibitor.
in Proceedings of the National Academy of Sciences of the United States of America
Gabaev I
(2014)
Expression of the human cytomegalovirus UL11 glycoprotein in viral infection and evaluation of its effect on virus-specific CD8 T cells.
in Journal of virology
Houldcroft CJ
(2020)
Assessing Anti-HCMV Cell Mediated Immune Responses in Transplant Recipients and Healthy Controls Using a Novel Functional Assay.
in Frontiers in cellular and infection microbiology
Hyde K
(2021)
Limited replication of human cytomegalovirus in a trophoblast cell line.
in The Journal of general virology
Karniely S
(2016)
Human Cytomegalovirus Infection Upregulates the Mitochondrial Transcription and Translation Machineries.
in mBio
Laib Sampaio K
(2016)
The contribution of pUL74 to growth of human cytomegalovirus is masked in the presence of RL13 and UL128 expression
in Journal of General Virology
Lau B
(2020)
Human Cytomegalovirus Long Non-coding RNA1.2 Suppresses Extracellular Release of the Pro-inflammatory Cytokine IL-6 by Blocking NF-?B Activation.
in Frontiers in cellular and infection microbiology
McLaren JE
(2019)
IL-33 Augments Virus-Specific Memory T Cell Inflation and Potentiates the Efficacy of an Attenuated Cytomegalovirus-Based Vaccine.
in Journal of immunology (Baltimore, Md. : 1950)
Murrell I
(2017)
The pentameric complex drives immunologically covert cell-cell transmission of wild-type human cytomegalovirus
in Proceedings of the National Academy of Sciences
Murrell I
(2016)
Genetic Stability of Bacterial Artificial Chromosome-Derived Human Cytomegalovirus during Culture In Vitro.
in Journal of virology
Nightingale K
(2018)
High-Definition Analysis of Host Protein Stability during Human Cytomegalovirus Infection Reveals Antiviral Factors and Viral Evasion Mechanisms.
in Cell host & microbe
O'Donnell VB
(2020)
Potential Role of Oral Rinses Targeting the Viral Lipid Envelope in SARS-CoV-2 Infection.
in Function (Oxford, England)
Patel M
(2018)
HCMV-Encoded NK Modulators: Lessons From in vitro and in vivo Genetic Variation.
in Frontiers in immunology
Scurr MJ
(2020)
Cancer Antigen Discovery Is Enabled by RNA Sequencing of Highly Purified Malignant and Nonmalignant Cells.
in Clinical cancer research : an official journal of the American Association for Cancer Research
Stanton RJ
(2014)
HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells.
in Cell host & microbe
Taher H
(2020)
In vitro and in vivo characterization of a recombinant rhesus cytomegalovirus containing a complete genome.
in PLoS pathogens
Uusi-Kerttula H
(2015)
Incorporation of Peptides Targeting EGFR and FGFR1 into the Adenoviral Fiber Knob Domain and Their Evaluation as Targeted Cancer Therapies.
in Human gene therapy
Vlahava VM
(2021)
Monoclonal antibodies targeting nonstructural viral antigens can activate ADCC against human cytomegalovirus.
in The Journal of clinical investigation
Wang ECY
(2018)
Suppression of costimulation by human cytomegalovirus promotes evasion of cellular immune defenses.
in Proceedings of the National Academy of Sciences of the United States of America
Weekes MP
(2014)
Quantitative temporal viromics: an approach to investigate host-pathogen interaction.
in Cell
Weiler N
(2021)
Role of Envelope Glycoprotein Complexes in Cell-Associated Spread of Human Cytomegalovirus.
in Viruses
Wilkinson GW
(2015)
Human cytomegalovirus: taking the strain.
in Medical microbiology and immunology
Description | A UK underpinning platform to study immunology and immunopathology of COVID-19:The UK Coronavirus Immunology Consortium |
Amount | £6,552,119 (GBP) |
Funding ID | MR/V028448/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 07/2020 |
End | 12/2022 |
Description | Collaborative grant |
Amount | £2,593,375 (GBP) |
Funding ID | 204870/Z/16/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2018 |
End | 06/2022 |
Description | Collaborative grant |
Amount | £1,704,805 (GBP) |
Funding ID | 209213/Z/17/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2018 |
End | 06/2023 |
Description | Covid Immunology Consortium |
Amount | £8,000,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 07/2019 |
End | 08/2021 |
Description | Development of a rapid, low cost Human Cytomegalovirus diagnostic |
Amount | £758,611 (GBP) |
Funding ID | II-LB-1117-20001 |
Organisation | National Institute for Health Research |
Sector | Public |
Country | United Kingdom |
Start | 11/2018 |
End | 10/2022 |
Description | Enhancing Efficiency of Therapeutic Antiviral Antibodies |
Amount | £50,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2020 |
End | 08/2021 |
Description | Exploiting Novel Antiviral Immune Responses |
Amount | £1,900,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2023 |
End | 04/2029 |
Description | GW4 PhD Studentship |
Amount | £80,000 (GBP) |
Organisation | GW4 |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2017 |
End | 04/2021 |
Description | GW4 Studentship |
Amount | £80,000 (GBP) |
Organisation | Cardiff University |
Sector | Academic/University |
Country | United Kingdom |
Start | 08/2017 |
End | 09/2021 |
Description | Health studentship |
Amount | £66,000 (GBP) |
Funding ID | HS-14-11 |
Organisation | Health and Care Research Wales |
Sector | Public |
Country | United Kingdom |
Start | 01/2015 |
End | 12/2017 |
Description | ISSF |
Amount | £50,000 (GBP) |
Organisation | Cardiff University |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2018 |
End | 04/2019 |
Description | ISSF |
Amount | £50,000 (GBP) |
Organisation | Cardiff University |
Sector | Academic/University |
Country | United Kingdom |
Start | 08/2019 |
End | 08/2020 |
Description | ISSF Seedcorn |
Amount | £40,000 (GBP) |
Organisation | Wellcome Trust |
Department | Wellcome Trust Strategic Award |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2016 |
End | 12/2016 |
Description | Identifying therapeutic combinations of antiviral antibodies |
Amount | £20,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 06/2020 |
End | 10/2020 |
Description | Impact Award |
Amount | £50,000 (GBP) |
Organisation | NRN |
Sector | Charity/Non Profit |
Country | Nepal |
Start | 08/2017 |
End | 09/2018 |
Description | Invention for Innovation |
Amount | £320,000 (GBP) |
Organisation | National Institute for Health Research |
Sector | Public |
Country | United Kingdom |
Start | 09/2014 |
End | 09/2017 |
Description | Investigating the role of mouthwashes in protecting from occupational SARS-CoV2 exposure |
Amount | £150,000 (GBP) |
Organisation | Venture Life |
Sector | Private |
Country | United Kingdom |
Start | 09/2019 |
End | 05/2021 |
Description | MRC Confidence in Concept |
Amount | £48,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2017 |
End | 03/2018 |
Description | MRC DTG |
Amount | £70,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2014 |
End | 09/2017 |
Description | MRC DTG |
Amount | £70,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2014 |
End | 09/2017 |
Description | Mapping the lipid envelope composition of SARS-CoV2 for reducing transmission, thrombosis and inflammation |
Amount | £604,006 (GBP) |
Funding ID | BB/W003376/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2021 |
End | 11/2022 |
Description | Modulating Immune Responses to Control Virus Infection |
Amount | £80,000 (GBP) |
Organisation | Health and Care Research Wales |
Sector | Public |
Country | United Kingdom |
Start | 01/2021 |
End | 12/2023 |
Description | NISCHR Cancer Centre |
Amount | £106,000 (GBP) |
Organisation | Health and Care Research Wales |
Sector | Public |
Country | United Kingdom |
Start |
Description | Project Grant |
Amount | £150,000 (GBP) |
Organisation | Sir Halley Stewart Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2014 |
End | 12/2015 |
Description | Project Grant |
Amount | £672,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 05/2014 |
End | 05/2017 |
Description | Project Grant |
Amount | £750,000 (GBP) |
Funding ID | MR/S00971X/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2019 |
End | 04/2022 |
Description | Research |
Amount | £180,000 (GBP) |
Organisation | Kymab |
Sector | Private |
Country | United Kingdom |
Start | 01/2019 |
End | 12/2019 |
Description | Research Infrastructure Fund |
Amount | £350,000 (GBP) |
Organisation | Cardiff University |
Sector | Academic/University |
Country | United Kingdom |
Start | 06/2017 |
End | 07/2022 |
Description | Role of ADCC in SARS-COV2 infection |
Amount | £70,000 (GBP) |
Organisation | Health and Care Research Wales |
Sector | Public |
Country | United Kingdom |
Start | 07/2020 |
End | 03/2021 |
Description | SIURI Studentship |
Amount | £80,000 (GBP) |
Organisation | Cardiff University |
Sector | Academic/University |
Country | United Kingdom |
Start | 08/2018 |
End | 09/2023 |
Description | SREF |
Amount | £20,000 (GBP) |
Organisation | Cardiff University |
Sector | Academic/University |
Country | United Kingdom |
Start |
Description | Ser Cymru studentship |
Amount | £70,000 (GBP) |
Organisation | Government of Wales |
Sector | Public |
Country | United Kingdom |
Start | 01/2014 |
End | 12/2016 |
Description | Supporting industry to meet the needs of the covid19 pandemic |
Amount | £150,000 (GBP) |
Organisation | European Commission |
Department | European Regional Development Fund (ERDF) |
Sector | Public |
Country | Belgium |
Start | 07/2020 |
End | 03/2022 |
Description | Systems Immunity PhD |
Amount | £80,000 (GBP) |
Organisation | Cardiff University |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2017 |
End | 09/2021 |
Description | Systems Immunity PhD Studentship |
Amount | £90,000 (GBP) |
Organisation | Cardiff University |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2018 |
End | 10/2022 |
Description | The Immunological and Virological Determinants of Long Covid |
Amount | £700,000 (GBP) |
Organisation | National Institute for Health Research |
Sector | Public |
Country | United Kingdom |
Start | 03/2022 |
Description | Wellcome ISSF |
Amount | £50,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2018 |
End | 03/2019 |
Description | Welsh Government Pathfinder |
Amount | £60,000 (GBP) |
Organisation | Government of Wales |
Sector | Public |
Country | United Kingdom |
Start | 01/2017 |
End | 12/2017 |
Title | Anti-viral therapeutic |
Description | The development of antibodies capable of controlling HCMV through ADCC. |
IP Reference | |
Protection | Patent application published |
Year Protection Granted | |
Licensed | Yes |
Impact | Licensing of IP to a commercial company. |
Title | METHODS AND COMPOSITIONS FOR THE TREATMENT OF HCMV |
Description | Provided herein are compositions and methods for the treatment of HCMV infection in a subject. |
IP Reference | WO2015073788 |
Protection | Patent application published |
Year Protection Granted | 2015 |
Licensed | Yes |
Impact | NA |
Description | Advisor to Welsh Scientific Minister on covid19 |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | I advised the Welsh chief scientific officer on the state of research internationally relating to covid19. |
Year(s) Of Engagement Activity | 2020,2021 |
Description | BBC Wales Today interview |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Interview on BBC Wales Today to highlight our research. Unknown as yet. |
Year(s) Of Engagement Activity | 2014 |
Description | Conference organiser UK CMV workshop |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | Organised a conference for all researchers within the Uk CMV field. |
Year(s) Of Engagement Activity | 2017 |
URL | http://ukcmv.cf.ac.uk |
Description | Discussing vaccine trials with media organisation |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Industry/Business |
Results and Impact | Discussed recent HCMV vaccine trials with a journalist from 'Globaldata', which produces industry publications. |
Year(s) Of Engagement Activity | 2017 |
Description | International herpesvirus conference (Japan) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Discussions with other researchers in the field. Email discussions with other researchers. |
Year(s) Of Engagement Activity | 2014 |
Description | International herpesvirus conference, Boise |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Presentation at international conference. |
Year(s) Of Engagement Activity | 2015 |
Description | Keynote presentation at IHW |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Keynote presentation at conference |
Year(s) Of Engagement Activity | 2019 |
Description | Media commentator on SARS-CoV2 |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | • Radio 5 live to discuss Christmas during covid • Institute for Welsh Affairs round-table to dissect the Welsh response to the pandemic • Chairing a panel discussion as part of European Researchers Night, celebrating covid research in Wales • Radio 5 live to discuss the Welsh vs English response to the pandemic • BBC to produce a 10 minute piece for social media 'busting the covid myths' • BBC News on the spread of SARS-CoV2 around the country • BBC News 24 on whether the government should have locked down sooner • Numerous appearances on Wales Online, Western Mail, and BBC Radio Wales, including on the need and effectiveness of lockdown, the need for the circuit breaker, whether the circuit breaker worked, what behaviours are 'safe' during covid, how Welsh Universities are supporting covid19 research, what the mutations seen in the virus mean, and what the vaccine means. • A talk to the Royal Society of Biology (South Wales) on covid19 • Panel member for BBC Eye on Wales 'Coronavirus, what lies ahead' • Panel member for BBC Science Café 'Finding cures for coronavirus' • Panel member for BBC Science Café 'Coronaviruses' • Live interview by 'Science made simple', for a piece aimed at explaining the pandemic to primary school children • ITV News on why Wales was seeing higher cases than England. • BBC Wales Tonight on the 'new variants' of covid • Produced social media clips on the topic of 'can my life go back to normal after the covid vaccine' |
Year(s) Of Engagement Activity | 2020,2021 |
Description | Meeting Chief Medical Officer |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | I met with the chief medical officer to discuss ways of improving patient awareness of congenital HCMV infection. |
Year(s) Of Engagement Activity | 2016 |
Description | Member of the 'Hospitality During Covid' group |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Industry/Business |
Results and Impact | I sat on a committee tasked with producing a set of nationally agreed safety guidelines for festivals during covid19, thus permitting them to obtain insurance for their event. |
Year(s) Of Engagement Activity | 2020,2021 |
Description | Member of the 'International Intelligence' subgroup of Welsh government 'Technical Advisory Group' |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | I site on the group responsible for informing ministers of how other countries are dealing with the covid19 pandemic, as a route to determine which actions will likely be successful in Wales. |
Year(s) Of Engagement Activity | 2020,2021 |
Description | Member of the 'Virology and Testing' subgroup of Welsh Government 'Technical Advisory Group' |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | I sit on the TAG subgroup responsible for advising ministers on issues relating to covid testing. |
Year(s) Of Engagement Activity | 2020,2021 |
Description | Microbiology Society Talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | Talk at a conference |
Year(s) Of Engagement Activity | 2017 |
Description | Mini-herpesvirus workshop |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Presentation at international conference. |
Year(s) Of Engagement Activity | 2015 |
Description | Plenary Speaker UK CMV Conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Plenary lecture at leading national conference. Discussions with peers. |
Year(s) Of Engagement Activity | 2014 |
Description | Press release |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Press release highlighting recent major funding successes. Unknown as yet. |
Year(s) Of Engagement Activity | 2014 |
Description | Provided a response to recommendations to UK Newborn Screening Committee on newborn HCMV screening |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | Provided responses as to whether universal screening of all newborns for HCMV, is practical and/or desirable. |
Year(s) Of Engagement Activity | 2017 |
Description | Society for General Microbiolgy annual meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Discussions with other researchers Speaker invites. |
Year(s) Of Engagement Activity | 2014 |
Description | Talk at CMV 2017 conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Talk at a conference |
Year(s) Of Engagement Activity | 2017 |
Description | University Seminar Series (UCL) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | Research seminar series |
Year(s) Of Engagement Activity | 2015 |