Studentship: Investigation into the effect of spike glycoprotein glycosylation for rational vaccine development
Lead Research Organisation:
THE PIRBRIGHT INSTITUTE
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
Infectious bronchitis virus (IBV) has four structural proteins; spike (S) glycoprotein, membrane (M) and envelope (E) proteins which are found in the lipid membrane surrounding the virus particle and the nucleocapsid (N) protein binds the positive-sense RNA genome. The S glycoprotein is highly glycosylated with N-linked high-mannose type oligosaccharides (Cavanagh et al., 1983) and mediates attachment of the virus to host cells and fusion of virus-cell and cell-cell. Previous work has shown that exchanging the spike of a strain of IBV for that from another strain can change the tropism of the recombinant virus.We wish to investigate the role of glycosylation of the S glycoprotein on infectivity and tropism of IBV for different cell types, both in vitro and in ovo for the development of novel vaccines.
Planned Impact
unavailable
Publications
Bickerton E
(2018)
The S2 Subunit of Infectious Bronchitis Virus Beaudette Is a Determinant of Cellular Tropism.
in Journal of virology
Bickerton E
(2014)
Cellular tropism of the infectious bronchitis virus spike glycoprotein
in 8th International Symposium on Avian Corona- and Pneumoviruses and complicating pathogens 2nd Annual Meeting of Cost Action FA1207, Rauischholzhausen, Germany
Keep S
(2016)
Animal Coronaviruses
Keep SM
(2015)
Transient dominant selection for the modification and generation of recombinant infectious bronchitis coronaviruses.
in Methods in molecular biology (Clifton, N.J.)
Maier HJ
(2015)
Preface. Coronaviruses.
in Methods in molecular biology (Clifton, N.J.)
Stevenson-Leggett P
(2020)
Treatment with Exogenous Trypsin Expands In Vitro Cellular Tropism of the Avian Coronavirus Infectious Bronchitis Virus.
in Viruses
Stevenson-Leggett P
(2021)
Analysis of the avian coronavirus spike protein reveals heterogeneity in the glycans present.
in The Journal of general virology
| Description | We have investigated the role of the spike glycoprotein of infectious bronchitis virus (IBV) in the ability of IBV to grow in different cell types and have developed our understanding of the spike's role in virus entry under different physiological conditions, including temperature and presence of different enzymes. We have established that the addition of exogenous protease during culture can expand the tropism of some IBV strains. We have generated a new vaccine candidate for IBV with a modified spike that can be grown in cell culture rather than viable hen's eggs. We have identified certain regions of the virus proteins that are modified by host cells and are important for antibody recognition. We have identified the glycans present on the spike glycoprotein of IBV. |
| Exploitation Route | These findings may be used for rational vaccine design. In particular, the new vaccine candidate will be investigated in a recently-started Follow-on Fund grant. If the candidate is deemed successful, it will remove the need for growing such a vaccine in hen's eggs, which will be advantageous for the vaccine industry. |
| Sectors | Agriculture Food and Drink Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
| Description | The findings have contributed to a successful BBSRC link grant application and have been presented at national and international conferences. We have been awarded BBSRC Follow-on Funding to continue this research into the development of vaccines against infectious bronchitis virus that can be produced in cell culture rather than eggs. Recent studies expressing coronavirus S proteins in mammalian and insect cells have identified a high level of glycosylation on the protein's surface. We used IBV propagated in embryonated hens' eggs to explore the glycan profile of viruses derived from infection in cells of the natural host, chickens. We identified multiple glycan types on the surface of the protein and found a strain-specific dependence on complex glycans for recognition of the S2 subunit by a monoclonal antibody in vitro, with no effect on viral replication following the chemical inhibition of complex glycosylation. We confirmed glycosylation at 18 sites by mass spectrometry for the pathogenic laboratory strain M41-CK. Further characterization revealed heterogeneity among the glycans present at six of these sites, indicating a difference in the glycan profile of individual S proteins on the IBV virion. Choice of cell type may be important for the expression of coronavirus spikes or stock viruses, to ensure that spike glycosylation resembles that observed during natural infection. |
| First Year Of Impact | 2019 |
| Sector | Agriculture, Food and Drink,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal |
| Description | Training MSc students |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | Delivered a new training session to MSc students teaching viral quantification assays. This lead to a greater understanding of laboratory techniques and academic research. |
| Description | BBSRC responsive mode link award |
| Amount | £1,382,000 (GBP) |
| Funding ID | BB/P019137/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2018 |
| End | 01/2021 |
| Description | Further development of infectious bronchitis virus vaccines adapted for production in cell culture |
| Amount | £262,701 (GBP) |
| Funding ID | BB/R019576/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2018 |
| End | 03/2020 |
| Description | Rational development of the next generation of vaccines for Infectious Bronchitis Virus |
| Amount | £155,538 (GBP) |
| Organisation | British Egg Marketing Board |
| Sector | Private |
| Country | United Kingdom |
| Start | 09/2024 |
| End | 09/2028 |
| Description | UK International coronavirus network (UK-ICN) |
| Amount | £510,207 (GBP) |
| Funding ID | BB/W003287/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2021 |
| End | 09/2025 |
| Description | Characterisation of IBV spike protein glycosylation using mass spectrometry |
| Organisation | University of Liverpool |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Preparation of purified IBV S protein samples for mass spectrometry analysis. |
| Collaborator Contribution | Analysis of samples by mass spectrometry to characterize glycans on the surface of the IBV S protein. |
| Impact | Identification and structural analysis of glycans on the surface of the IBV S protein. |
| Start Year | 2017 |
| Description | Collaboration with University of Bristol |
| Organisation | University of Bristol |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We are collaborating on a PhD studentship to investigate "Rational development of the next generation of vaccines for Infectious Bronchitis Virus". We have sourced the funding and are hosting the student. |
| Collaborator Contribution | Our partners at Bristol are supervising the PhD student and we have monthly meetings to discuss project progress. |
| Impact | None yet. |
| Start Year | 2024 |
| Description | Partnering with National Taiwan University |
| Organisation | National Taiwan University |
| Country | Taiwan, Province of China |
| Sector | Academic/University |
| PI Contribution | We have prepared and submitted an application for a BBSRC-Taiwan Partnering Award to study "Assembly of Recombinant Infectious Bronchitis Virus and Determination of Antigenic Sites that Confer Hemagglutination Activity". |
| Collaborator Contribution | The partners conceived the project and got in contact about submitting an application for funding together. |
| Impact | An application has been made for a BBSRC-Taiwan Partnering Award in November 2018. |
| Start Year | 2018 |
| Description | Attendance of South Wiltshire Virology Group Meeting (University of Surrey) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Industry/Business |
| Results and Impact | Scientists attended the meeting in Surrey and heard oral presentations from experts in the field as well as students and early career researchers. The event encouraged networking between colleagues and potential collaborators from other institutes and universities. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Avian Immunity and Genetics Meeting |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Industry/Business |
| Results and Impact | The meeting consisted of oral and poster presentations from researchers in the field of avian immunity and genetics. I presented a poster which encouraged discussion around my project. |
| Year(s) Of Engagement Activity | 2017 |
| Description | BSI webinar |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | I presented a webinar hosted by the British Society for Immunology entitled "BSI Coronavirus webinar: What can we learn from the animal coronaviruses?", which sparked questions and discussions afterwards. I have since been contacted to establish new collaborations with people in the audience. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Careers fair |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Students from several schools in the region attended the careers fair where we had a stall. Several students requested information about apprenticeships and were interested in possible careers in science. |
| Year(s) Of Engagement Activity | 2011,2012,2013,2014,2015,2016,2017 |
| Description | Centre of excellence for research on avian diseases (CERAD) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | I was invited to present my work at the UK-China Centre of excellence for research on avian diseases (CERAD) meeting attended by researchers from UK, China and Thailand. There was lots of discussion about the research and future directions, including potential collaborations. |
| Year(s) Of Engagement Activity | 2017 |
| Description | European COST Action FA1207 Early Stage Researchers Meeting (Uppsala, Sweden) |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | 15 postgraduate students from different European laboratories (all researching avian coronaviruses) attended a small focus group meeting to discuss the creation of a network for the PhD students in these research groups. This was designed to encourage inter-group collaboration and to facilitate knowledge exchange between different groups with different expertise. The visit consisted of several forums where the expertise of each group were identified and opportunities for collaboration were discussed. |
| Year(s) Of Engagement Activity | 2015 |
| Description | International Day of Women and Girls in Science |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | I gave a quote as a STEM ambassador about why I think it is important to make sure women and girls have the same opportunities in STEM. This was shared on social media to celebrate International Day of Women and Girls in Science, a UN-led initiative. |
| Year(s) Of Engagement Activity | 2019 |
| Description | International Women's Day video for social media |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Three team members were interviewed about their careers in science for International Women's Day. The videos were posted on Pirbright's website, Facebook and Twitter to celebrate what we love about working in science. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Interview for national newspaper |
| 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 with a journalist from The Telegraph about coronavirus replication and transmission. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Interview with Associated Press |
| 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 | Interview with a journalist from Associated Press about coronavirus research at The Pirbright Institute. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Interview with BBC Radio Surrey |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Interview with journalists from BBC Radio Surrey on the breakfast show about coronavirus research at The Pirbright Institute. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Interview with BuzzFeed News |
| 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 | Interview with a journalist from BuzzFeed News about coronavirus research at The Pirbright Institute. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Invited seminar speaker |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Other audiences |
| Results and Impact | Erica Bickerton was invited to give a seminar at Imperial College London, which sparked questions and discussion afterwards. |
| Year(s) Of Engagement Activity | 2017 |
| Description | MSc student visit |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Postgraduate students |
| Results and Impact | I hosted several MSc students from University of Surrey, discussed avian research with them and demonstrated some laboratory techniques. The students gained an understanding of academic research and laboratory work. |
| Year(s) Of Engagement Activity | 2018,2019 |
| Description | Microbiology Society Annual conference (UK) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | At each conference I presented a poster describing a particular aspect of my project. The poster sessions were open to all participants at the conference and so the audience included researchers from many different areas of science. This provides a platform to promote my research to a wider audience as well as discuss the key findings with experts in my own field. |
| Year(s) Of Engagement Activity | 2013,2015,2016 |
| Description | Microbiology Society Annual conference (UK) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Poster or oral presentation at Microbiology Society annual conference, a major international event. The participants included researchers from many different areas of science. This provides a platform to promote research to a wider audience as well as discuss the key findings with experts in my own field. |
| Year(s) Of Engagement Activity | 2010,2011,2012,2013,2014,2015,2016,2017,2018,2019 |
| Description | Microbiology Society Avian Focus Meeting (London, UK) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | I gave a 15 minute oral presentation about a part of my PhD project to an audience of around 80 people. The audience consisted of researchers from many different scientific institutions from different areas of avian research. This was a great opportunity to present my work to experts in this field and gain novel insights into the project and the possible applications of my work. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Microbiology Society Avian Focus Meeting (UK) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | I gave a 15 minute oral presentation to an audience of around 80 people in 2016 and 2018. The audience consisted of researchers from many different scientific institutions from different areas of avian research. This was a great opportunity to present to experts in this field and gain novel insights into the project and the possible applications of my work. |
| Year(s) Of Engagement Activity | 2016,2018 |
| Description | Nidovirus symposium |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | I presented my work at the Nidovirus Symposium, which is held every three years and brings together researchers from industry and academia from many different countries. I had some interesting discussions with other researchers and built my network. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Opening of The Biggs Avian Research Facility |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | We presented our research and spoke to guests attending the opening of the Biggs Avian Research Facility at Pirbright. Guests who attended included politicians and members of the public from the local area, eminent researchers from other institutions, and members of BBSRC. Guests reported that they felt much more informed about the work going on at Pirbright and were impressed by our facilities. |
| Year(s) Of Engagement Activity | 2023 |
| Description | Pirbright Institute Student Day |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | I presented a poster describing my work to the student body and supervisors. This generated discussion and collaboration between different groups within the Institute. |
| Year(s) Of Engagement Activity | 2015,2016 |
| Description | Positive Strand Viruses Conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | This was a poster presentation. There were several different poster sessions at the conference allowing a large selection of people to view each poster. The audience included world leaders in my research field and important names from groups all over the world. This gave me the opportunity to discuss my work with other scientists on a one to one basis, leading to generation of new ideas for future experiments and collaborations. |
| Year(s) Of Engagement Activity | 2010,2013,2016,2019 |
| Description | Positive Strand Viruses Conference (Austin, Texas, USA) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | This was a poster presentation about the work involved in my PhD project. There were several different poster sessions at the conference allowing a large selection of people to view each poster. The audience included world leaders in my research field and important names from groups all over the world. This gave me the opportunity to discuss my work with other scientists on a one to one basis, leading to generation of new ideas for future experiments and collaborations. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Poster presentation at Global Alliance for Research on Avian Diseases international conference (Hanoi, Vietnam) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Approximately 80 people attended the event held over 3 days. The poster encouraged discussion about the project and potential collaborations between experts in the field. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Poster presentation at the International Nidovirus Symposium (Kansas City, MO, USA) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Presentation of a poster to the conference delegate including experts in the fields of nidovirus and glycosylation research. The presentation sparked discussion with numerous participants and led to collaboration with one. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Presentation at American Society for Virology conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited to give a keynote talk on "Rational vaccine design for the avian coronavirus infectious bronchitis virus" at the ASV Satellite Symposium: Viral Pathogenesis and Prevention in Animals, discussed research and future plans with other researches in the field. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Presentation at Global Alliance for Research on Avian Diseases Conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Presentation of my research at the Global Alliance for Research on Avian Diseases Conference in Vietnam to approximately 80 conference participants resulted in discussions about future research directions. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Presentation at RIVR meetings |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | Presentation of my research at Recently Independent Virology Researchers (RIVR) meetings in 2016, 2017, 2018, 2019 and 2020. I discussed my work and future collaborations with other virology researchers working in the UK. |
| Year(s) Of Engagement Activity | 2016,2017,2018,2019,2020 |
| Description | Presentation to BBSRC Executive Board |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | I presented our research to the BBSRC Executive Board when they visited The Pirbright Institute in September 2018 and discussed the impacts of our work.. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Presentations at Microbiology Society focused conference on Avian Infectious Diseases |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | The Microbiology Society supported a focused meeting on avian infectious disease research, bringing together scientists from all over the world to discuss their research. We gave presentations on "Characterisation of the Infectious Bronchitis Virus E Protein for Rational Vaccine Design" and "Rational vaccine design for the avian coronavirus infectious bronchitis virus", received good feedback on our work and ideas for future research. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Reverse genetics seminar (University of Surrey) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Postgraduate students |
| Results and Impact | A seminar was given based upon the reverse genetics system of infectious bronchitis virus. The audience was a group of 10 -15 MSc students from University of Surrey. The students were engaged, asked questions about the research and careers in science. We were asked to repeat the seminar for the next year's intake of students. |
| Year(s) Of Engagement Activity | 2013,2014,2015,2016,2017,2018 |
| Description | School visit (Compton, West Berkshire) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | The school visits included working with small groups of a-level biology students demonstrating a technique in the curriculum. They were encouraged to ask us questions about our work and how we use the technique as well as trying it out for themselves. |
| Year(s) Of Engagement Activity | 2012,2013,2014,2015 |
| Description | School visit (Compton, West Berkshire) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | The school visit included working with small groups of a-level biology students demonstrating a technique in the curriculum. They were encouraged to ask us questions about our work and how we use the technique as well as trying it out for themselves. |
| Year(s) Of Engagement Activity | 2013,2015 |
| Description | Teentech |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | The annual Teentech student science event in Guildford aims to encourage teenagers to consider science subjects and science careers. Our stand had considerable interest from the schoolchildren who were very enthusiastic. The event stimulated an increased interest in science and research. |
| Year(s) Of Engagement Activity | 2016,2019 |
| Description | organised workshops at Microbiology Society annual conferences 2014 - 2018 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | I co-organised virology division workshops on viral evolution and diversity and RNA viruses with colleagues from the virology division. The workshops were held at the annual Microbiology Society conferences in spring each year. Organisation involved selecting abstracts for oral or poster presentation, ordering the presentations and chairing the sessions. |
| Year(s) Of Engagement Activity | 2015,2016,2017,2018 |