Further development of an African swine fever virus live attenuated vaccine
Lead Research Organisation:
The Pirbright Institute
Department Name: Vector-borne Viral Diseases
Abstract
African swine fever virus (ASFV) causes a severe disease of domestic pigs that can result in up to 100% mortality and has severe socio-economic impacts. ASFV is endemic in most sub-Saharan African countries and Sardinia. Since introduction of ASF in 2007 to Georgia, the disease has rapidly spread through the Russian Federation and the risk of further spread has increased. The lack of a vaccine limits options for disease control. Attenuated ASFV strain OURT88/3 induces good levels of protection in pigs against lethal challenge with virulent virus. Commercial development of this strain as a vaccine has been hampered by the lack of a suitable cell line to propagate the virus. We have now identified a pig macrophage cell line can be infected by OURT88/3 strain and the virus grown in these cells can still induce protection in pigs. We will investigate the use of this cell line for ASFV vaccine strain production and diagnosis. We will also identify partners for commercial development
Publications
Wileman T
(2016)
Encyclopedia of Cell Biology
Sánchez-Cordón PJ
(2017)
Different routes and doses influence protection in pigs immunised with the naturally attenuated African swine fever virus isolate OURT88/3.
in Antiviral research
Reis AL
(2017)
Unraveling the Armor of a Killer: Evasion of Host Defenses by African Swine Fever Virus.
in Journal of virology
Sánchez-Cordón PJ
(2018)
African swine fever: A re-emerging viral disease threatening the global pig industry.
in Veterinary journal (London, England : 1997)
Montaner-Tarbes S
(2019)
Serum-Derived Extracellular Vesicles from African Swine Fever Virus-Infected Pigs Selectively Recruit Viral and Porcine Proteins.
in Viruses
| Description | The registration of vaccines requires evaluation of their safety and efficacy at different doses. To evaluate if the naturally attenuated ASFV strain OURT88/3 may meet these requirements we carried out an experiment in which we immunised groups of pigs with different doses (10 e3, 10 e4, 10 e5) and by either intramuscular or intranasal routes. Pigs received a boost immunisation of the same dose and by the same route and were challenged with a virulent isolate in parallel with a group of non-immune pigs. The results showed that the pigs immunised with the two lower doses by the intranasal route were all protected whereas in other groups protection varied between 33% and 66%. Adverse reactions were more severe at the higher dose. The results suggest that the oral/nasal route may be a more effective delivery route. This route may be most useful for delivery of vaccine by bait to wild boar or to piglets. The protection induced by OURT88/3 was compared with that induced by two ASFV gene deletion mutants. Rational attenuation of virus by deletion of genes would provide a route to construct a vaccine for any of the different genotypes circulating, for example in E. Europe. The results showed these 2 deletion mutants could induce good levels of protection and are promising candidates for further study. Further evaluation of these gene deleted ASFV in the genotype I strain Benin97/1 has included comparison of clinical signs and levels of protection observed following delivery of different doses and by different routes (Intramuscular and Intranasal). In addition a study was carried out to determine duration of immunity over a period of 130 days. |
| Exploitation Route | Funding has been obtained for further development of vaccine candidates for Africa from GALVmed (Global Alliance for Livestock Veterinary Medicines) and for vaccines from Europe from a veterinary vaccine company (Zoetis). A patent has been applied for and granted by OAPI African countries. This application is under review by other patent examiners in the EU and USA. |
| Sectors | Agriculture, Food and Drink |
| Description | The results from the award will support the commercial development of a vaccine for African swine fever virus thus helping to protect the UK and global pig industry from this devastating pig disease. |
| Sector | Agriculture, Food and Drink |
| Impact Types | Economic |
| Description | Science Director Global Alliance for African swine fever virus research |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | I was Science Director of the Global Alliance for Research on African swine fever virus (GARA). This involved being Chair of the Scientific Organizing Committee for 2 International Meetings and preparing reports and GAP analysis to direct research. |
| URL | https://www.ars.usda.gov/GARA/ |
| Description | GALVmed DFID Funding |
| Amount | £1,000,000 (GBP) |
| Organisation | GALVmed |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2016 |
| End | 03/2022 |
| Description | Zoetis Research Funding |
| Amount | £550,000 (GBP) |
| Organisation | Zoetis |
| Sector | Private |
| Country | United States |
| Start | 04/2017 |
| End | 10/2018 |
| Description | Collaboration on ASFV immune evasion genes |
| Organisation | Gulbenkian Institute of Science |
| Country | Portugal |
| Sector | Academic/University |
| PI Contribution | Assays of ASFV immune evasion genes in macrophages. |
| Collaborator Contribution | Information of ASFV immune evasion genes from Dr Mike Parkhouse |
| Impact | Multi-disciplinary involving molecular and cell biology and virology. 1 publication |
| Start Year | 2007 |
| Description | Mapping ligand binding domain on African swine fever virus CD2v protein |
| Organisation | University of Oxford |
| Department | Weatherall Institute of Molecular Medicine (WIMM) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Testing of mutant versions of CD2v extracellular domain for ability to bind to red blood cells |
| Collaborator Contribution | Produced predicted model of CD2v extracellular domain and selected mutations to be made |
| Impact | Preliminary results for publication and future funding application |
| Start Year | 2018 |
| Title | ATTENUATED AFRICAN SWINE FEVER VIRUS VACCINE |
| Description | The present invention provides an attenuated African Swine Fever (ASF) virus which lacks a functional version of the following genes: multigene-family 360 genes 9L, 10L, 11L, 12L, 13L and 14L; and multigene-family 505 genes 1R, 2R, 3R and 4R. The invention further provides an attenuated African Swine Fever (ASF) virus which lacks a functional version of the DP148R gene. The present invention also provides a vaccine comprising such an attenuated virus and its use to prevent ASF. Further, the invention relates to intranasal administration of an attenuated ASF virus. |
| IP Reference | WO2015193685 |
| Protection | Patent application published |
| Year Protection Granted | 2015 |
| Licensed | No |
| Impact | We have initiated a collaboration with Zoetis and GALVmed which has brought new funding to the project. |
| Description | Agritech Forum Kiev Ukraine |
| 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 was invited by the UK Department of Trade and Industry to attend an Agritech Business Forum in Kiev Ukraine. I gave a presentation at a workshiop they organised and met with Ukrainian businesses, Vets, Policy makers and Farmers |
| Year(s) Of Engagement Activity | 2016 |
| Description | BBC World Service Science Programme "Science in Action" Broadcast |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | This was an broadcast with BBC World Service Science in Action Programme to inform the public about the current African swine fever situation and provide information on pathogenesis mechanisms of transmission and our research on vaccine development |
| Year(s) Of Engagement Activity | 2018 |
| URL | http://www.bbc.co.uk/programmes/p002vsn |
| Description | Broadcast on African swine fever on BBC wolrd service "The Food Chain" |
| 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 | Public/other audiences |
| Results and Impact | Interview with BBC World Service "The Food Chain" on African swine fever virus. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.bbc.co.uk/programmes/p05xhflj |
| Description | Communication on Understanding Animal Research |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | I gave a presentation and discussed with students at Woking College my work and more generally in use of animals in research. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Expert panel on African swine fever virus whole genome sequencing and bioinformatics |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | Member of expert working group to discuss methods for African swine fever virus complete genome sequencing . Attendance at working group meeting in Nairobi Kenya. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Inreview with Daily Telegraph about African swine fever |
| 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 | Public/other audiences |
| Results and Impact | Interview with reporter from Daily Telegraph about African swine fever virus and risks to UK farmers |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.telegraph.co.uk/news/2018/12/12/uk-farmers-warned-alert-african-swine-fever-virus-hits-e... |
| Description | Interview with BBC Radio 4 Inside Science |
| 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 | Public/other audiences |
| Results and Impact | An interview with BBC Radio 4 Inside Science producers to inform them about African swine fever virus and our research on vaccine development |
| Year(s) Of Engagement Activity | 2018 |
| URL | http://www.bbc.co.uk/programmes/p05v91jq |
| Description | Interview with Health for Animals about African swine fever vrius vaccine development and current situation |
| 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 | Industry/Business |
| Results and Impact | Interview with journalists from Health for Animals about African swine fever vaccine research published in a newsletter sent to 200 people. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://healthforanimals.org/resources-and-events/newsletter-repository/17-disease-outbreaks.html?q=... |
| Description | Interview with IEG Policay about ASFV vaccines |
| 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 | Policymakers/politicians |
| Results and Impact | Interview with Peter Rixon of IEG policy about the prospects for development of vaccines for African swine fever vrius |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://iegvu.agribusinessintelligence.informa.com/CO221819/ASF-outbreak-in-Belgium-highlights-lack-... |
| Description | Invited Keynote Speaker International Society of Veterinary Epidemiology and Ecology, China Mai Thailand |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Keynote talk on progress towards African swin efever virus vaccine development at ISVEE meeting Thailand |
| Year(s) Of Engagement Activity | 2018 |
| Description | Laboratory Training to Postgraduate MSC students |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | Training and knowledge exchange to MSC Veterinary Microbiology students from Surrey University |
| Year(s) Of Engagement Activity | 2016 |
| Description | Member of Expert Group on Roadmap and Blueprint for an African swine fever vrius vaccine |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | I was a member of an EU commissioned working group on preparation of a Roadmap and Blueprint for an African swine fever virus vaccine. The group comprised ~ 15 experts. One 2 day face to face meeting, a telephone conference were held in addition to preparation of a 36 page report. The aim of the ASF blueprint and roadmap is to give an overview of the research efforts needed and help to direct investments towards specific areas. The STRATEGIC GOALS identified include: •Identification of potential strategies for vaccine development based on existing data/knowledge in a view of an effective and safe vaccine. •Identification of gaps and needs for vaccine development and manufacturing following the Good Manufacturing Practice Standards. •Identification of a network of dedicated laboratories directed towards vaccine development •Identification of the research steps (Roadmap) The report has been published on the EU website http://ec.europa.eu/food/sites/food/files/safety/docs/cff_animal_vet-progs_asf_blue-print-road-map.pdf |
| Year(s) Of Engagement Activity | 2016,2017 |
| URL | http://ec.europa.eu/food/sites/food/files/safety/docs/cff_animal_vet-progs_asf_blue-print-road-map.p... |
| Description | Organising Committee EPIZONE Annual Workshop |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I have been a member of the scientific organizing committee of the EU EPIZONE Network every year since its founding in 2005 except for 2015. |
| Year(s) Of Engagement Activity | 2006,2007,2008,2009,2010,2011,2012,2013,2014,2016 |
| URL | http://www.epizone-eu.net |
| Description | Participation in Understanding Animal Research Video |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Interviewed and filmed by Understanding Animal Research as part of their 360 degree tour of UK animal facilities (http://www.labanimaltour.org/) |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.labanimaltour.org/ |
| Description | Preparation of presentation on African swine fever clinical signs and pathogenesis |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Prepared a presentation on African swine fever clinical signs and pathogenesis aimed at making farmers and veterinary practitioners aware. Presentation made available publically on the APHA, DEFRA and Pirbright websites. A follow up video was made by APHA and training for APHA veterinary services is planned |
| Year(s) Of Engagement Activity | 2018 |
| URL | http://apha.defra.gov.uk/documents/surveillance/diseases/african-swine-fever-images.pdf |
| Description | Provided information to Podcast This week in Virology about African swine fever virus spread in wild boar |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | E-mail correspondence providing advice to presenters of TWIV This week in Virology Podcast. |
| Year(s) Of Engagement Activity | 2019 |
| URL | http://www.microbe.tv/twiv/twiv-532/ |
| Description | Representative at Pig and Poultry Fair, Stoneleigh UK |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | I represented The Pirbright Institute at a Stand at the Pig and Poultry Fair, Stoneleigh Warwickshire and discussed with farmers, vets, policy makers, schools |
| Year(s) Of Engagement Activity | 2016 |
| Description | Seminar on African swine fever virus |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Presentation on African swine fever virus vaccine development to Yebio Bioengineering and China Animal Health and Epidemiology Centre, Qingdao, PR China |
| Year(s) Of Engagement Activity | 2018 |
| Description | Seminar on African swine fever virus |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Seminar on African swine fever virus host interactions and vaccine development. Yangzhou University Veterinary Faculty PR China |
| Year(s) Of Engagement Activity | 2018 |
| Description | Seminar on African swine fever virus |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Seminar at Beijing Institute of Animal Sciences, Chinese Academy of Agricultural Sciences 12 Zhongguanchan South Stree, Haifing District Beijing |
| Year(s) Of Engagement Activity | 2018 |
| Description | Seminar on African swine fever virus virus host interaction and vaccine development |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Seminar on African swine fever virus evasion of host defences and vaccine development Institute of Molecular and Cellular Biology, UCL London |
| Year(s) Of Engagement Activity | 2018 |
| Description | Seminar on African swine fever virus virus host interaction and vaccine development |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Seminar Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences PR China |
| Year(s) Of Engagement Activity | 2018 |
| Description | Seminar on prospects for African swine fever virus vaccine development |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Seminar at Harbin Institute for Veterinary Research, PR China |
| Year(s) Of Engagement Activity | 2018 |
| Description | Seminar on virus host interactions and prospects for African swine fever virus vaccine development |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | Seminar on African swine fever virus host interactions and vaccine development |
| Year(s) Of Engagement Activity | 2018 |
| Description | Visit to QIA Institute S Korea |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Visit to QIA Institute S Korea to provide expert advice on ASFV |
| Year(s) Of Engagement Activity | 2013 |
| Description | Visiting Scientist from CReSA Barcelona |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | A postgraduate student from CReSA Barcelona visited for collaborative research and training for 6 months |
| Year(s) Of Engagement Activity | 2016 |