Combating highly pathogenic avian influenza: Novel vaccination strategies using recombinant live avian viral vaccine vectors

Lead Research Organisation: The Pirbright Institute
Department Name: UNLISTED

Abstract

Combating highly pathogenic avian influenza: Novel vaccination strategies using recombinant live avian viral vaccine vectors. Avian influenza (AI) viruses (or the 'avian flu' as it is commonly called) naturally exist in wild birds such as waterfowl and shore birds where the virus is highly diverse and generally not pathogenic. These low pathogenic avian influenza (LPAI) viruses routinely cross over from the wild-bird reservoir and infect domestic poultry, frequently becoming highly pathogenic viruses (HPAI), which are extremely dangerous to commercial poultry and are occasionally fatal to humans. In the recent outbreaks of HPAI viruses of H5 and H7 subtypes in many parts of the world, including the EU, more than 200 million domestic poultry have either died or been culled, impecting huge socio-economic costs. The current epidemic of HPAI H5N1 originating from south East Asia and recently transmitted over long distances via migratory birds is unprecedented. The magnitude of risk that migratory birds are posing to the United Kingdom and other EU countries is not clear, however, there is growing evidence (recent death of migratory swan by H5N1 in Fife, Scotland) suggesting that the prevention and control of AI disease outbreak in poultry and other captive birds will be a major challenge for many years to come. To date the main strategy for controlling HPAI in domestic poultry in UK and in some other countries has been eradication of the virus by large scale culling of infected and contact flocks. However, the current world-wide epidemic has severely affected the economies of developed as well as developing countries. Therefore, for ethical, ecological and economic reasons, it is no longer considered acceptable to control and eradicate AI mainly by the mass killing of animals. As a result the European Parliament, the World Organization for Animal Health (OIE) and Food and Agriculture Organization (FAO) have allowed not only emergency vaccination, following disease outbreak, but also preventive vaccination as an additional tools for the control of AI. Currently, the available AI inactivated vaccines are produced in embryonated eggs and have several disadvantages. We propose to develop novel vaccines using some of the state of the art biotechnological tools. These will allow the administration of live viral vaccines as single injection either at hatch or into eggs before they hatch (in ovo vaccination). These new improved vaccines will be safe, effective and economical, and above all protect the commercial poultry and other domestic birds from disease and dissemination of AI viruses into the environment, consequently preventing AI virus spread, averting the looming global pandemic threat.

Technical Summary

We propose to use novel approaches for AI vaccination using recombinant herpesvirus of turkey (HVT) and avian infectious bronchitis virus (IBV) as vaccine vectors that express protective haemagglutinin (HA) and neuraminidase (NA) antigens of avian influenza virus. Since these vaccine constructs will express only selected AI antigen, vaccinated birds can be unambiguously differentiated from those infected with the field virus. These virus vectors have several distinct advantages: (1) they are extensively used as live virus vaccines. (2) they induce immunity following in ovo vaccine application. (3) it is relatively easy to generate new vaccines from the specific field isolates. Recombinant HVT and IBV vectors will be generated by cloning HA and NA genes (the multiple basic amino acids at the HA1 & HA2 cleavage sites will be deleted) from the HPAI viruses, [A/os/Italy 984/00 (H7N1) and A/ty/Turkey/1/05 (H5N1)], into the HVT and IBV genomes using in house derived reverse genetics systems. We plan to generate a panel of recombinant viruses (1) HVT/H7/N1 (2) HVT/H5/N1 (3) IBV/H7 (4) IBV/H5 (5) IBV/N1 for use as potential vaccine candidates. The recombinant viruses will be evaluated for expression of the AI-derived HA and NA genes in cell culture and in ovo. Selected viruses will be used in homologous virus challenge studies in chickens for comparison with commercially available inactivated vaccines. The protection parameters of the vaccines candidates will be assessed by comparing the immune responses, mortality rates, morbidity and shedding of AI virus from the challenged birds. The data obtained from these experiments will enable us to select the most effective vaccine candidate providing protection against challenge with HPAI AI virus and decrease in excretion of the AI virus. Ultimately, we anticipate that these novel AI vaccines will be used in the eradication of AI by the control of disease and reduction of viral load in the environment.
 
Description We have demonstrated regional and global changes in TCR alpha beta T cell repertoires in the gut depending on the complexity of the enteric microflora. We have also demonstrated the development of recombinant viral vectors for immunizing against avian influenza
Exploitation Route Controlling avian influenza by vaccination in endemic countries such as Vietnam
Sectors Agriculture, Food and Drink,Environment

 
Description Innovations in control of avian infectious diseases for sustainable growth and food security in low and middle income countries
Amount £355,000 (GBP)
Organisation The Royal Society 
Sector Academic/University
Country United Kingdom
Start 12/2016 
End 11/2021
 
Description Studentship Identification of genetic markers in the haemagglutinin glycoprotein critical for antigenic activity of H9N2
Amount £118,000 (GBP)
Funding ID BBS/E/I/00001759 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2015 
End 09/2019
 
Description UK-China partnership on Global Food Security: Combating avian tumor diseases for sustainable poultry proudction
Amount £382,000 (GBP)
Funding ID BB/R007632/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2018 
End 03/2020
 
Title CRISPR/Cas9-based gene editing of avian herpesvirus vectors to develop novel recombinant vaccines 
Description Development of recombinant herpesvirus vaccines are usually achieved by classical homologous recombination methods. The advent of new genome editing tools has enabled its application on avian herpesvirus vaccine strains to develop new recombinant vaccines potentially capable of expressing protective antigens from multiple pathogens 
Type Of Material Technology assay or reagent 
Year Produced 2017 
Provided To Others? Yes  
Impact The major impact will be in the generation of novel vaccines that can simultaneously protect against multiple avian diseases 
URL http://www.poultryworld.net/Health/Articles/2016/12/Is-GM-technology-the-future-of-poultry-vaccines-...
 
Description Global Alliance for Research on Avian Diseases 
Organisation Global Alliance for Research on Avian Diseases
PI Contribution This alliance led by Pirbright has participation from over 40 countries and comprises of academics and industry professionals. This forum helps in working together, identifies the challenges and opportunities for improved control of avian diseases
Collaborator Contribution Two successful international meetings were organised as part of this alliance, one in London in 2015 and most recent one in Hanoi, Vietnam in January 2018
Impact Organisation of two successful international meetings and development of significant collaborations
Start Year 2015
 
Description Invitation to participate in the Vaccine Innovation Forum 2017 at Shanghai 26-27 April 2017 
Organisation Chinese Academy of Agricultural Sciences
Department Shanghai Veterinary Research Institute
PI Contribution Prof. Nair was invited to participate in the Vaccine Innovation Forum 2017 at Shanghai 26-27 April 2017 to present a talk on 'Novel Vaccine Development for Avian Virus Diseases'. He also participated in the round table discussions on the challenges and opportunities in the vaccines and vaccination sector
Collaborator Contribution Vaccine Innovation Forum will help in expanding the future collaborations and activities of the UK-China Centre of Excellence for Research on Avian Diseases (http://www.uk-china-cerad.org/).
Impact organised joint meeting in China and the UK to discuss on challenges and opportunities
Start Year 2017
 
Description Presentation at the Microbiology Society meeting 
Organisation Microbiology Society
Country Unknown 
Sector Learned Society 
PI Contribution PhD student presented her work at the meeting
Collaborator Contribution The partners organised the meeting
Impact Keshalini Sabaratnam presented the poster on 'The interaction between the MDV neurovirulence factor pp14 and the host transcription regulator, CREB3' at the Society's annual meeting
Start Year 2016
 
Description UK Korea collaboration 
Organisation Seoul National University
Country Korea, Republic of 
Sector Academic/University 
PI Contribution This collaboration has brought in Pirbright Institute's experience in Virology
Collaborator Contribution Partner's experience in genetics and genomics as well as gene editing and transgenic technology
Impact The visits by the Seoul partners to Pirbright and subsequent discussions on research collaboration has initiated a number of projects. This has also led to the award of the Royal Society International Professorship to Prof. Nair and Prof. Jae Yong Han from Seoul National University
Start Year 2015
 
Description Chaired the Poultry Disease group meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Poultry Disease group is a forum of veterinary practitioners to discuss the advances in poultry diseases that could be translated from research labs to the farms
Year(s) Of Engagement Activity 2017
 
Description Inauguration of the UK-China Centre of Excellence for Research on Avian Diseases (CERAD) and Symposium on Recent Advances in Avian Disease Research 
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 Inauguration of the UK-China Centre of Excellence for Research on Avian Diseases (CERAD) and Symposium on Recent Advances in Avian Disease Research. This was held in Binzhou, Shandong province in China in 2015
Year(s) Of Engagement Activity 2015
 
Description Invitation to give keynote talk on 'Control of avian diseases: Challenges and opportunities' 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave the Keynote talk on 'Control of avian diseases: Challenges and opportunities' at this International Symposium organized with an aim to gather international virology experts from both human and veterinary fields to share research experience, update findings and contribute their expertise through presentation and interactive discussion. The topics will cover a wide range of virology research common in both human and animal aspects. In addition, technological platforms such as vaccine development, and novel assays will be emphasized and addressed.
Year(s) Of Engagement Activity 2018
URL http://www.biotec.or.th/virus-symposium2018/index.php
 
Description Organised the 3rd UK-China CERAD meeting in Guildford, UK in July 2017 
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 The 3rd UK-China CERAD meeting helped to bring together professional from both countries to identify challenges and exploit the opportunities for improved control of poultry diseases and increasing food security.
Year(s) Of Engagement Activity 2017
URL http://www.uk-china-cerad.org/
 
Description Poultry Health course 
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 Poultry Health Course is run as a residential and online course to transfer recent advances in avian disease research from the laboratory to the field.
Year(s) Of Engagement Activity Pre-2006
URL http://www.poultryhealthcourse.com/
 
Description Second Symposium of the UK-China Centre of Excellence for Research on Avian Diseases held in March 2016 in Binzhou, Shandong Province, China 
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 The second international meeting of the UK-China CERAD was attended by a number of delegates from both UK and China and reviewed the progress. Plans were drawn of further activities and plans for securing additional grants.
Year(s) Of Engagement Activity 2016
 
Description UK-Malaysia Vaccinology Workshop (Malaysia) 
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 This workshop aimed to build long-term and sustainable links between scientists in the UK and Malaysia working on/have interests in veterinary vaccines. This workshop has encouraged early career researchers from veterinary, biological and social sciences to understand the ever-increasing threats to global food security from infectious animal diseases and their control using next generation vaccine strategies.
Year(s) Of Engagement Activity 2016
URL http://ukmalaysiaworkshop.co.uk/