ANIHWA call 1: MADISUP. Marek's Disease Virus induced immunosuppression: From diagnosis to vaccination
Lead Research Organisation:
The Pirbright Institute
Department Name: Avian Viral Diseases
Abstract
Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes high economic losses in poultry production. Beside acute death or extensive tumor formation, MDV induces immunosuppression (IS) thus increasing the susceptibility of chickens to other pathogens. Besides being an issue of animal health and welfare, it increases the need for pharmacological treatment and also for the frequency of vaccination against multitude of pathogens, as MDV infection was shown to strongly reduce vaccine responses. Furthermore, MDV vaccines themselves induce mild IS, as such causing a dilemma between the absolute necessity of a MDV vaccination and the reduced response to other vaccines.
Though the phenomenon of IS has been recognised for decades, very little is known about the mechanisms behind MDV-induced IS to date. Our goal is to apply the unique expertise and the techniques developed over the last years by the consortium on MDV and chicken immunology to identify the basic mechanisms associated with IS, and to develop novel MDV vaccines with significantly reduced immunosuppressive properties.
Though the phenomenon of IS has been recognised for decades, very little is known about the mechanisms behind MDV-induced IS to date. Our goal is to apply the unique expertise and the techniques developed over the last years by the consortium on MDV and chicken immunology to identify the basic mechanisms associated with IS, and to develop novel MDV vaccines with significantly reduced immunosuppressive properties.
Technical Summary
Though the phenomenon of immunosuppression (IS) has been recognised for decades, very little is known about the mechanisms behind MDV-induced IS to date. In this project, we aim to examine the basis of IS in MD infection. Evaluation of MDV-induced IS is currently restricted
to the measurement of thymus and bursa atrophy, a gross and inaccurate method, which can only be performed post-mortem. Therefore, there is a definite need for establishing novel diagnostic tools that facilitate a quantitation of immunosuppressive effects that can be applied to a large scale in poultry production. In the differnt workpackages, we will examine (1) the modulation of the innate and adaptive immune system by evaluating the role of NK cells, and by studying the differential leukogram profiles, (2) role of lymphocyte death as a cause of IS, (3) dynamics of interactions of vaccine viruses in the avian embryo, and finally (4) opportunities of evaluating novel vaccine candidates that do not induce immunosuppression.
to the measurement of thymus and bursa atrophy, a gross and inaccurate method, which can only be performed post-mortem. Therefore, there is a definite need for establishing novel diagnostic tools that facilitate a quantitation of immunosuppressive effects that can be applied to a large scale in poultry production. In the differnt workpackages, we will examine (1) the modulation of the innate and adaptive immune system by evaluating the role of NK cells, and by studying the differential leukogram profiles, (2) role of lymphocyte death as a cause of IS, (3) dynamics of interactions of vaccine viruses in the avian embryo, and finally (4) opportunities of evaluating novel vaccine candidates that do not induce immunosuppression.
Planned Impact
By targeting virus-induced immunosuppression, our project aims at understanding the mechanisms. A better knowledge of the immunossuppressive effects of the virus help in devising methods/strategies for preventing losses from the disease. A vaccine that would have reduced immunosuppressive effects will have immense potential in preventing losses and reducing losses and improving welfare. The proposed research will benefit the poultry industry as an improved understanding of the molecular mechanisms of MDV immunosuppression could lead to new strategies of control. Judging from the interest in the lay press, there is a considerable interest among the public for the scientific understanding of how some diseases produce damage to animal health. What will be done to ensure that they have the opportunity to benefit from this research? A special attention will be paid to the exploitation of results as this project will identify genes, molecular and cellular mechanisms which may be at the origin of industrial developments. A consortium agreement will be engaged and negotiated through the institutional representative of each partner. Material rights may concern cell-lines or vaccines which may arise as breakthrough developments from WP1 - 2 and 4. The project aims mainly to target the poultry vaccine market with a promising new offer in MDV replication process that can be monitored in vitro and therefore that can lead to a better production and control of the poultry vaccines.
People |
ORCID iD |
Venugopal Nair (Principal Investigator) |
Publications
Reddy VRAP
(2019)
In vitro Interactions of Chicken Programmed Cell Death 1 (PD-1) and PD-1 Ligand-1 (PD-L1).
in Frontiers in cellular and infection microbiology
Tang N
(2019)
Generating Recombinant Avian Herpesvirus Vectors with CRISPR/Cas9 Gene Editing.
in Journal of visualized experiments : JoVE
Bondada MS
(2019)
Multifunctional miR-155 Pathway in Avian Oncogenic Virus-Induced Neoplastic Diseases.
in Non-coding RNA
Tang N
(2021)
Application of CRISPR-Cas9 Editing for Virus Engineering and the Development of Recombinant Viral Vaccines
in The CRISPR Journal
Denesvre C
(2016)
Marek's disease virus undergoes complete morphogenesis after reactivation in a T-lymphoblastoid cell line transformed by recombinant fluorescent marker virus.
in The Journal of general virology
Description | Marek's disease virus-induced immunosuppression was more prominent with the HVT vaccine rather than the CVI988 (Rispens) vaccine. Our studies also provided evidence for apoptosis and innate responses in response to in ovo vaccination with HVT and CVI988 vaccines, as well as recombinant HVT IBDV VP2 vaccines. While the role of different cell types were demonstrated, the observed decrease in macrophage numbers may be due to a lack of stimuli for maintaining the antigen-presenting process leading to macrophage destruction. |
Exploitation Route | Improving the approaches of developing better vaccines |
Sectors | Agriculture, Food and Drink |
Description | Contributing to the chapter on Marek's disease for the OIE Terrestrial Manual |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
Impact | The contribution to the Terrestrial Manual on the recent advances in the diagnosis and control of Marek's disease will impact on improved and better control of the disease to reduce losses and improved food security |
URL | http://www.oie.int/ |
Description | Participation in the Management of the Oxford DTP |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | As part of the Management committee of the Oxford-Pirbright-Oxford Brookes-Diamond doctorate Training Partnership, contributed to the success of the DTP in meeting the objectives, recruitment and review |
URL | http://www.biodtp.ox.ac.uk/ |
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 | Charity/Non Profit |
Country | United Kingdom |
Start | 12/2016 |
End | 11/2021 |
Description | Marek's Disease Virus induced immunosuppression |
Amount | £395,000 (GBP) |
Funding ID | BB/LK014262/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2014 |
End | 09/2017 |
Title | CRISPR/Cas9-based gene editing pipeline for generation of recombinant herpesvirus vaccines or targeted editing |
Description | CRISPR/Cas9-based gene editing pipe line was established for rapid generation of recombinant herpesvirus vaccines, which involves the use of stable Cas-9 expressing cell lines or through transient Cas9 expression |
Type Of Material | Technology assay or reagent |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | The major impact of this will be enabling advanced research in developing new innovative vaccines for successful and effective control of avian diseases for enhancing global food security |
URL | https://www.jove.com/video/58193/generating-recombinant-avian-herpesvirus-vectors-with-crisprcas9-ge... |
Description | Collaboration with Harbin Veterinary Research Institute China |
Organisation | Chinese Academy of Agricultural Sciences |
Department | Harbin Veterinary Research Institute (HVRI) |
Country | China |
Sector | Public |
PI Contribution | We had intellectual input in formulating the research programme |
Collaborator Contribution | The partners visited Pirbright and set up collaborative research plans and signed a memorandum of understanding |
Impact | Output or outcomes are yet to materialize. But we had one joint publication |
Start Year | 2014 |
Description | OIE Reference Laboratory |
Organisation | World Organisation for Animal Health, France |
Country | France |
Sector | Public |
PI Contribution | As the Reference Lab, we have contributed to the diagnostic procedures and preparation of manual |
Collaborator Contribution | Collaborators has published our activities and prepared the book |
Impact | Publication of the Manual on diagnostic tests |
Title | A METHOD FOR PRODUCING AVIAN LEUKOSIS VIRUS(ALV)-RESISTANT AVIAN LINE USING CRISPR/CAS9 SYSTEM |
Description | Patent describes a method for generating avian leukosis virus-resistant chicken line using CRISPR/Cas9-based gene editing approaches |
IP Reference | 10-2018-0011871 Korea |
Protection | Patent application published |
Year Protection Granted | 2018 |
Licensed | Commercial In Confidence |
Impact | The technology allows introduction of de novo genetic resistance against avian leukosis viruses using gene editing technologies |
Title | Multivalent recombinant vaccines |
Description | The use of CRISPR/Cas9-based technology for the development of recombinant vaccines against poultry diseases |
IP Reference | EP19218804 |
Protection | Patent application published |
Year Protection Granted | |
Licensed | Commercial In Confidence |
Impact | The technology will impact on translation of the technology for commercial development of poultry disease vaccines |
Description | AN INTERVIEW WITH PROFESSOR VENUGOPAL NAIR |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Professor Venugopal Nair is a Research Group Leader at The Pirbright Institute, a visiting Professor of Avian Virology at the Department of Zoology, and a Jenner Investigator at the Jenner Institute, University of Oxford. He is also a member of the Microbiology Society, and in this interview, he tells us more about his research into viral diseases of livestock. |
Year(s) Of Engagement Activity | 2020 |
URL | https://microbiologysociety.org/membership/meet-our-members/focus-area-viruses/an-interview-with-pro... |
Description | Avian Genetics and Immunity (University of Surrey) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | The Symposium on Avian Genetics and Immunity is being to engage international audience with interests on avian genetics and immunity |
Year(s) Of Engagement Activity | 2017 |
URL | http://geneticsandimmunity.com |
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 | Interview for CGTN on the importance of poultry disease control in China and the significance of collaboration |
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 | It was an interview by the editor for CGTN on the contribution of Pirbright and the Chinese collaborations on controlling poultry diseases and improving avian health |
Year(s) Of Engagement Activity | 2020 |
URL | https://newseu.cgtn.com/news/2020-01-28/British-and-Chinese-scientists-join-forces-to-fight-avian-di... |
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 | Invitation to talk at the Vaccine Symposium "Vaccines at different levels of complexity from subunit to whole cell formulations" jointly organised by the Centre of Genomic Regulation (CRG), Radboud UMC and MSD Animal Health, with the support from the MycoSynVac project |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Gave a talk and participated in the discussion on the challenges and research opportunities for innovation in poultry disease control |
Year(s) Of Engagement Activity | 2017 |
URL | http://www.crg.eu/ |
Description | Invited talk on 20th World Vaccine Congress Washington on 28th September 2020 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited talk on 'Novel vaccine technique to target multiple poultry diseases using CRISPR/Cas9 system' at the 20th World Vaccine Congress in Washington |
Year(s) Of Engagement Activity | 2020 |
URL | https://www.terrapinn.com/conference/world-vaccine-congress-washington/index.stm |
Description | Invited talk on 28th September 2020 on ''Challenges and opportunities for control of infectious animal diseases including zoonosis' |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | International Webinar of 'Epistemological approaches to animal disease control programmes with special reference to rabies' |
Year(s) Of Engagement Activity | 2020 |
Description | Keynote talk at the World Veterinary Poultry Association meeting |
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 the keynote talk on 'Avian tumour viruses: their contribution to our understanding of cancer' at the World Veterinary Poultry Association XXth Congress in Edinburgh |
Year(s) Of Engagement Activity | 2017 |
URL | http://www.wvpac2017.com/ |
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 | Presentation on the effects on oncogenic virus infection at the Veterinarian's Forum, Namakkal, India on 29 Dec 2018 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | The purpose of the engagement was to update the practicing poultry veterinarians on the problems with oncogenic virus diseases and methods of control. The meeting attended by nearly 100 veterinarians was very informative and ended with a long discussion on the challenges and innovations |
Year(s) Of Engagement Activity | 2018 |