Further development of infectious bronchitis virus vaccines adapted for production in cell culture
Abstract
Infectious bronchitis virus (IBV) causes a respiratory disease in chickens making them more susceptible to bacterial infections. Chickens infected with IBV gain less weight and produce fewer high quality eggs. It is important to vaccinate against IBV both for welfare and economic reasons. Many fertilised chicken eggs are used to produce vaccines against IBV. Egg-based vaccine production has numerous disadvantages. We have identified a method to produce live vaccines on a cell line which is beneficial to the vaccine industry as well as the poultry industry, reducing the number of eggs utilised in vaccine production; an important consideration under the principles of the 3Rs. Vaccine production on cell lines is faster and more efficient than on eggs and large volumes of vaccine can be produced. We aim to further develop this method to generate vaccines against IBV that can be produced in cell culture and to license these products to a commercial partner.
Publications
Conceicao C
(2020)
The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins.
in PLoS biology
Keep S
(2022)
A Temperature-Sensitive Recombinant of Avian Coronavirus Infectious Bronchitis Virus Provides Complete Protection against Homologous Challenge
in Journal of Virology
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 assessed the efficacy of two vaccine candidates against IBV that can be propagated in cell culture. The vaccine viruses have been characterised in vivo and the amounts of IBV-specific and neutralising antibodies present in vaccinated chickens have been quantified and compared for each virus. In vivo virus tropism has been analysed in infected tissues. The presence of immune markers following vaccination and challenge has been assessed using immunohistochemistry techniques and analysed by a pathologist. A technique for enabling IBV replication in cell culture has also been optimised, allowing for increased virus yields in cell culture with the addition of exogenous protease. This work has recently been published in the journal, Viruses. Three recombinant viruses containing cell culture modifications in the S2 subunit have been generated by reverse genetics. The growth and genetic stability of the viruses are being analysed in different cell types in vitro. |
| Exploitation Route | We are talking to veterinary pharmaceutical companies about the potential for licensing the new vaccine candidates. IBV vaccines that can be propagated in cell culture would be beneficial to industry, making vaccine manufacture more efficient and reducing the reliance on hen's eggs. This is also an important consideration under the 3Rs. The ability of IBV field strains to replicate in cell culture with the addition of exogenous protease will allow a greater range of IBV strains to be studied in the lab |
| Sectors | Agriculture, Food and Drink,Manufacturing, including Industrial Biotechology |
| Description | Results of this research have been presented at national and international conferences, facilitating networking and discussion of future collaborations. We have discussed the findings with contacts in the poultry industry and are seeking ways to take the development of live attenuated IBV vaccines that can be propagated in cell culture forward in collaboration with industry. We have also continued to develop the results of this grant in an undergraduate placement project, providing training to the next generation of molecular virology researchers and experience of working in a laboratory. |
| First Year Of Impact | 2020 |
| Sector | Agriculture, Food and Drink,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| 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 | Training of 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 | 21ROMITIGATIONFUND Pirbright Institute |
| Amount | £283,000 (GBP) |
| Funding ID | BB/W510725/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2021 |
| End | 03/2022 |
| Description | SOMAmer technology to diagnose coronavirus infection: veterinary and zoonotic implications |
| Amount | £1 (GBP) |
| Organisation | University of Oxford |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 10/2021 |
| End | 09/2025 |
| Description | Taiwan Partnering Award |
| Amount | £40,700 (GBP) |
| Funding ID | BB/S020624/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| 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 | 10/2021 |
| End | 09/2025 |
| 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 | Ash Manor School challenge week workshop |
| 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 | For this event, 60 students were rotating around a series of science workshops as part of their challenge week based on a selected theme of their choice. Giulia and Phoebe contributed together with other people from our Institute in delivering the workshop about microbiology, hence student were actively interested in the topic. They organised activities that could be performed in small groups such as teaching pupils about the importance of hand hygiene using our UV Equipment, seeing live mosquitoes through a microscope, learning about flu using our Flu Fighters- H&N Selector and trying to take swabs from a model chicken using Flu Fighters- Henrietta the Chicken. The students were very interested in all the activities and actively participating, and they were asking many questions related to viruses, animal diseases, zoonotic diseases and microbiology in general. |
| Year(s) Of Engagement Activity | 2019 |
| 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 | 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 | MSc Student group visit to The Pirbright Institute |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | A group of 8 MSc students from the University of Surrey visited The Pirbright Institute to learn different techniques in virology research. This included a short presentation about different methods of virus quantification followed by practical training in the lab for all students. This sparked a lot of questions about the technique and our research. The students were able to list the benefits and limitations of the technique by the end of the session. Some students said they planned to return to the Institute to complete short research projects in the summer. |
| Year(s) Of Engagement Activity | 2020 |
| 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 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 | 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 | 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 | 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 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 of results to potential industry partners |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | I presented some of my results in a short presentation to two representatives from a vaccine company. This sparked questions about the applications of the research in an industrial setting to boost vaccine virus yields and also some suggestions were made about further experiments for more tailored results to the company. |
| Year(s) Of Engagement Activity | 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 | Presentations at the UK International Coronavirus Network (UK-ICN) AGM |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | We presented research "The Genetic Stability, Replication Kinetics and Cytopathogenicity of Recombinant Avian Coronaviruses with a T16A or an A26F Mutation within the E Protein Is Cell-Type Dependent" and "A temperature sensitive recombinant of avian coronavirus infectious bronchitis virus provides complete protection against homologous challenge" and a poster on "A novel in-cell micro neutralisation assay for the human coronavirus OC-43: Allowing rapid and automated quantification of neutralising effect of antibodies and antiviral compounds" at the annual general meeting of the UK-ICN in Cambridge. We networked with other researchers working in the coronavirus field and discussed future research. |
| Year(s) Of Engagement Activity | 2022 |
| Description | STEM Student Challenge Day (Farnborough College) |
| 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 | 40 pupils attended the event from different schools to participate in different activities meant to reflect the science involved in vaccine research, sparking questions about the different steps involved in finding a vaccine candidate and the roles we play in these steps. Students asked about potential opportunities for work experience in the laboratory and which subjects are suitable for studying virology at university. |
| Year(s) Of Engagement Activity | 2020 |
| Description | School Visit (Ash Manor) |
| 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 | High school aged 13-14 were involved in an interactive session where they had the chance to learn about different areas of research at The Pirbright Institute, including swabbing for influenza viruses and looking at mosquitoes under a light microscope. They were able to ask questions about our research and our roles at the organisation. |
| Year(s) Of Engagement Activity | 2019 |
| 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 |