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
 
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 £216,000 (GBP)
Organisation GALVmed 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2016 
End 09/2017
 
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 Lourinhã Museum
Department 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
 
Title Gene-deleted live attenuated African swine fever vaccine candidate 
Description We identified African swine fever virus genes that inhibit the host interferon antiviral response and showed that deletion of these from the virus genome attenuates the virus and can lead to induction of protection against challenge. Thus we identified a route to construct candidate live attenuated vaccines. 
IP Reference Patent PCT/GB2015/051798 
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
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 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 
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 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 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 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 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