Understanding the immune mechanism of host disease resistance and development of marker vaccines and DIVA tests for Peste des Petits Ruminants (PPR)
Lead Research Organisation:
The Pirbright Institute
Department Name: Livestock Viral Diseases
Abstract
Peste des petits ruminants (PPR), also known as 'goat plague', is a highly contagious viral disease of sheep and goats. The direct economic losses of this disease have been estimated to be INR 1800 million (US$ 39 million) annually in India alone, whilst globally, >60% of the small ruminant population is considered at risk. However little is known about the pathogenesis of PPRV. Importantly, the primary site of viral replication has yet to be properly defined and the mechanism of the contrasting host specific disease resistance to PPR is unknown. Effective live attenuated vaccines are available to control PPR and a c-ELISA kit, to monitor the antibody response against the H protein, has been developed at IVRI and Pirbright. However, the critical drawback of these vaccines and associated c-ELISA kits is their inability to differentiate infection in vaccinated animals (DIVA) that slows down the implementation of PPR control through vaccination.
We hypothesise that PPRV infects immune cells of the respiratory mucosa, which then migrate to T-cell-rich areas of local lymphoid organs, from which virus enters the general circulation. We aim to develop a recombinant live attenuated DIVA vaccine that will be aerosolised to the primary viral replication site and is capable of generating a rapid and appropriate immune response including mucosal immunity. By further characterising the immune mechanisms underlying the differential susceptibility of sheep, goats and large ruminants to PPRV infection we aim to enhance our understanding of disease resistance mechanisms that will enable the development of better vaccines for the control of PPRV.
Aims and objectives: Three complementary research objectives are necessary to advance the ability to control and eradicate PPR: 1) understand PPRV pathogenesis in the pre-viraemic stage to identify the primary site of virus replication as a target for vaccination; 2) further characterise the immune response to PPR in small and large ruminants to understand differential disease resistance; and 3) develop appropriate PPR marker vaccines with associated DIVA tests to provide effective and targeted PPR control, ultimately leading to eradication from India.
Research approaches: Similar to our Nigeria75/1 GFP vaccine virus rescue, a virulent recombinant PPR virus containing the GFP gene will be constructed and rescued. This virus will be aerosolised to infect goats. Tissues will be collected from respiratory mucosa and associated lymph nodes and the primary viral replication site will be located by auto fluorescence of GFP and by IHC in tissues. Subsequent vaccinations will use the intranasal route if we define the primary replication site of PPRV during the pre-viremic stage. Using reverse genetics techniques we will develop two negative marker vaccines against Indian PPRV (Sungri 96- goat origin and Arasur 1987- sheep origin). Epitope deletion of a region of the H protein critical for monoclonal antibody binding will allow serological differentiation between vaccinated and naturally infected animals using the current cH-ELISA. For simple and rapid field diagnosis, we intend to develop loop mediated isothermal amplification assay (LAMP) and a lateral flow device. Real-time RT-PCR assay and biosensor assay development and validation in India will help the PPR control programme.
Interrogation of the immune mechanisms that underlie the differential susceptibility of species / breeds of small and large ruminants to PPRV will be carried forward using an unbiased transcriptomics approach.
Increasing our knowledge on early pathogenesis, using a marker vaccine to generate an appropriate immune response and the ability to differentiate infection from vaccination, in combination with a deeper understanding of immune function will enable the control of PPRV. This project will help in delivering PPR control in India and elsewhere by bringing together major players in PPR research in India and the UK.
We hypothesise that PPRV infects immune cells of the respiratory mucosa, which then migrate to T-cell-rich areas of local lymphoid organs, from which virus enters the general circulation. We aim to develop a recombinant live attenuated DIVA vaccine that will be aerosolised to the primary viral replication site and is capable of generating a rapid and appropriate immune response including mucosal immunity. By further characterising the immune mechanisms underlying the differential susceptibility of sheep, goats and large ruminants to PPRV infection we aim to enhance our understanding of disease resistance mechanisms that will enable the development of better vaccines for the control of PPRV.
Aims and objectives: Three complementary research objectives are necessary to advance the ability to control and eradicate PPR: 1) understand PPRV pathogenesis in the pre-viraemic stage to identify the primary site of virus replication as a target for vaccination; 2) further characterise the immune response to PPR in small and large ruminants to understand differential disease resistance; and 3) develop appropriate PPR marker vaccines with associated DIVA tests to provide effective and targeted PPR control, ultimately leading to eradication from India.
Research approaches: Similar to our Nigeria75/1 GFP vaccine virus rescue, a virulent recombinant PPR virus containing the GFP gene will be constructed and rescued. This virus will be aerosolised to infect goats. Tissues will be collected from respiratory mucosa and associated lymph nodes and the primary viral replication site will be located by auto fluorescence of GFP and by IHC in tissues. Subsequent vaccinations will use the intranasal route if we define the primary replication site of PPRV during the pre-viremic stage. Using reverse genetics techniques we will develop two negative marker vaccines against Indian PPRV (Sungri 96- goat origin and Arasur 1987- sheep origin). Epitope deletion of a region of the H protein critical for monoclonal antibody binding will allow serological differentiation between vaccinated and naturally infected animals using the current cH-ELISA. For simple and rapid field diagnosis, we intend to develop loop mediated isothermal amplification assay (LAMP) and a lateral flow device. Real-time RT-PCR assay and biosensor assay development and validation in India will help the PPR control programme.
Interrogation of the immune mechanisms that underlie the differential susceptibility of species / breeds of small and large ruminants to PPRV will be carried forward using an unbiased transcriptomics approach.
Increasing our knowledge on early pathogenesis, using a marker vaccine to generate an appropriate immune response and the ability to differentiate infection from vaccination, in combination with a deeper understanding of immune function will enable the control of PPRV. This project will help in delivering PPR control in India and elsewhere by bringing together major players in PPR research in India and the UK.
Technical Summary
Peste des petits ruminants (PPR) is a highly contagious viral disease of sheep and goats. However little is known about the pathogenesis of PPRV. Importantly, the primary site of viral replication has yet to be properly defined and the mechanism of the contrasting host specific disease resistance to PPR is unknown. Effective live attenuated vaccines are available to control PPR and a c-ELISA kit, to monitor the antibody response against the H protein. However, the critical drawback of these vaccines and associated c-ELISA kits is their inability to differentiate infection in vaccinated animals (DIVA) that slows down the implementation of PPR control through vaccination. Pirbright Institute (PIR) has already rescued the Nigeria 75/1 vaccine strain using reverse genetics techniques. Using the phage display peptide library screening technique, this vaccine has been negatively marked after mutating the epitope recognised by the monoclonal antibody used in the H ELISA. However, this vaccine cannot be used in India due to regulatory requirements of the Indian Government. Therefore, this project will use the above successful techniques to develop similar marker vaccines against contemporary Indian vaccine strains (Sungeri 96 and Arasur 87). Further, it is essential to know the primary site of virus replication for PPR infection for targeted vaccination to generate the rapid and appropriate immune response. Therefore, a virulent recombinant PPR virus containing the GFP will be aerosolised to infect goats and the primary viral replication site will be located by auto fluorescence of GFP and by IHC in tissues. Furthermore, understanding the immune mechanisms underlying the differential susceptibility of sheep, goats using an unbiased transcriptomics approach will enhance our understanding of disease resistance mechanisms.
Planned Impact
PPR remains endemic in developing countries in Asia, Middle East and Africa except South Africa that do not control borders and animal movements, nor vaccinate systematically on a large scale. PPR is a highly contagious viral disease of sheep and goats. The direct economic losses of this disease have been estimated to be INR 1800 million (US$ 39 million) annually in India alone, whilst globally, >60% of the small ruminant population is considered at risk. Vaccination is key to PPR control plans and eventual eradication in India and other endemic countries. Effective live attenuated vaccines are available to control PPR and a c-ELISA kit, to monitor the antibody response against the H protein. However, the critical drawback of these vaccines and associated c-ELISA kits is their inability to differentiate infection in vaccinated animals (DIVA) that slows down the implementation of PPR control through vaccination.
This project will support UK policy on food security, major investment in India on PPR control, and the research aims of the Global PPR Research Alliance (GPRA) for future eradication. It will strengthen multidisciplinary collaborations between science and industry, virology, molecular biology, mathematics and epidemiology. The complementary partnership will diversify the impact, broadening scientific outreach and providing channels to influence both policy and implementation of disease control.
As World Reference Laboratory for PPR, PIR is the global coordinating centre for labs engaged in regional PPR control activities mainly by training personels from endemic countries . IVRI in India work as National reference laboratory for PPR in India and is responsible for PPR control in India. OIE and FAO both are actively engaged in control policy of PPR throughout world. For the first time after seeing the devastating situation in DRC, OIE has established a PPR vaccine bank to help countries for control through vaccination. Recently PPR has spread to European part of Turkey and Northern Africa and become a threat to whole Europe. The common wildlife present in Europe and Turkey may bring the disease to Europe any time. EC is recently concern about this and recognise the role of wildlife for PPR spread.
PI at Pir has already developed a marker vaccine for Nigeria/75/1 PPR vaccine strain. However this cannot be used in India due to regulation imposed by Government. Therefore marker vaccine development for Indian vaccine strain is the main objective of this project. With the existing experience of reverse genetics techniques, the project will able to produce marker vaccine for PPR in India. The existing tests both at IVRI and Pirbright will work as DIVA test as the epitope against monoclonal used in this test will be mutated in vaccine virus. Therefore the test will work as a DIVA test and can detect infection in vaccinated animals. The other benefit from project will be to start a targeted vaccination targeting the primary replication site of virus in natural infection. This will generate a quick immune response in animals. The cause of this host specific disease resistance in PPR is unknown. Therefore characterisation of the immune response to PPR in small and large ruminants to understand differential disease resistance is necessary. Exploring this complete / relative disease resistant phenomenon across species / breeds may offer an alternate strategy for disease control with the following advantages.
1.Recommendation of particular resistant breeds in high disease prone areas
2.Selection of individuals that have high levels of disease resistance or tolerance for breeding purposes, if molecular markers are identified
3.Gene 'interogression' through cross-breeding to introduce 'resistant' genes into susceptible breeds
This project will support UK policy on food security, major investment in India on PPR control, and the research aims of the Global PPR Research Alliance (GPRA) for future eradication. It will strengthen multidisciplinary collaborations between science and industry, virology, molecular biology, mathematics and epidemiology. The complementary partnership will diversify the impact, broadening scientific outreach and providing channels to influence both policy and implementation of disease control.
As World Reference Laboratory for PPR, PIR is the global coordinating centre for labs engaged in regional PPR control activities mainly by training personels from endemic countries . IVRI in India work as National reference laboratory for PPR in India and is responsible for PPR control in India. OIE and FAO both are actively engaged in control policy of PPR throughout world. For the first time after seeing the devastating situation in DRC, OIE has established a PPR vaccine bank to help countries for control through vaccination. Recently PPR has spread to European part of Turkey and Northern Africa and become a threat to whole Europe. The common wildlife present in Europe and Turkey may bring the disease to Europe any time. EC is recently concern about this and recognise the role of wildlife for PPR spread.
PI at Pir has already developed a marker vaccine for Nigeria/75/1 PPR vaccine strain. However this cannot be used in India due to regulation imposed by Government. Therefore marker vaccine development for Indian vaccine strain is the main objective of this project. With the existing experience of reverse genetics techniques, the project will able to produce marker vaccine for PPR in India. The existing tests both at IVRI and Pirbright will work as DIVA test as the epitope against monoclonal used in this test will be mutated in vaccine virus. Therefore the test will work as a DIVA test and can detect infection in vaccinated animals. The other benefit from project will be to start a targeted vaccination targeting the primary replication site of virus in natural infection. This will generate a quick immune response in animals. The cause of this host specific disease resistance in PPR is unknown. Therefore characterisation of the immune response to PPR in small and large ruminants to understand differential disease resistance is necessary. Exploring this complete / relative disease resistant phenomenon across species / breeds may offer an alternate strategy for disease control with the following advantages.
1.Recommendation of particular resistant breeds in high disease prone areas
2.Selection of individuals that have high levels of disease resistance or tolerance for breeding purposes, if molecular markers are identified
3.Gene 'interogression' through cross-breeding to introduce 'resistant' genes into susceptible breeds
Publications
Abubakar M
(2017)
Serological Detection of Antibodies to Peste des Petits Ruminants Virus in Large Ruminants.
in Transboundary and emerging diseases
Altan E
(2019)
Molecular characterization of Peste des petits ruminants viruses in the Marmara Region of Turkey.
in Transboundary and emerging diseases
Brüning-Richardson A
(2016)
Mononegaviruses of veterinary importance. Volume 2: molecular epidemiology and control
Clarke BD
(2018)
Molecular detection, isolation and characterization of Peste-des-petits ruminants virus from goat milk from outbreaks in Bangladesh and its implication for eradication strategy.
in Transboundary and emerging diseases
Dhanasekaran S
(2014)
Toll-like receptor responses to Peste des petits ruminants virus in goats and water buffalo.
in PloS one
Fine A
(2020)
Eradication of Peste des Petits Ruminants Virus and the Wildlife-Livestock Interface
in Frontiers in Veterinary Science
Getachew B
(2018)
Monoclonal antibody resistant mutant of Peste des petits ruminants vaccine virus.
in Virusdisease
Kumar KS
(2014)
Molecular characterisation of lineage IV peste des petits ruminants virus using multi gene sequence data.
in Veterinary microbiology
| Description | 1. Researchers ( Satya Parida group) at The Pirbright Institute, together with partners in India, have developed a peste des petits ruminants virus (PPRV) vaccine that will be the first to differentiate between infected and vaccinated animals (DIVA). The DIVA vaccine virus was produced using a synthetic cDNA copy of the full-length genome of PPRV, which produces virus when introduced into cells. This vaccine has been tested in goats where it was shown to be both safe and effective in providing protection when the goats were infected with virulent PPRV. In contrast to the current vaccine, this new DIVA vaccine can differentiate between naturally infected and vaccinated animals based on antibody responses, serology. This will be extremely beneficial in the assessment of vaccine coverage and epidemiological surveillance, increasing the efficiency of control programmes. The work was funded by a Farmed Animal Disease and Health (FADH) grant joint funded by the Biotechnology and Biological Sciences Research Council (BBSRC), ISP host for satya and ISP CCG for animal ( Goats) experments and the Indian Government's Department of Biotechnology (DBT) and carried out in collaboration with Tamil Nadu Veterinary and Animal Sciences University (TANUVAS), Indian Veterinary Research Institute (IVRI), National Institute of Animal Biotechnology (NIAB) and National Institute of Veterinary Epidemiology and Disease Informatics (NIVEDI) and a patent application has been filed. 2. Little is known about the early events in the development of peste des petits ruminants virus (PPRV) infection. The current dogma is that PPRV replicates primarily in the epithelium of the respiratory tract before disseminating throughout the host, similarly to rinderpest virus (RPV). However, our investigations using intranasal inoculation of a recombinant PPRV containing Green Fluorescent Protein (GFP) indicate this is not the case. The PPRV-GFP virus is made from a synthetic cDNA copy of virus obtained from field isolates (PPRV/Mor-08), which produces virus when introduced into cells. GFP emits green light when stimulated by ultraviolet light and so can be visualized using florescence microscopy. Infection with the recombinant PPRV-GFP virus shows that immune cells in the pharyngeal tonsil are the primary target for infection, not epithelial cells. This is a ground-breaking discovery which changes our understanding of PPR pathogenesis. The research was funded by a Farmed Animal Disease and Health (FADH) grant joint funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Indian Government's Department of Biotechnology (DBT) and ISP Virus and ISP CCG for animal experiments. 2. Little is known about the early events in the development of peste des petits ruminants virus (PPRV) infection. The current dogma is that PPRV replicates primarily in the epithelium of the respiratory tract before disseminating throughout the host, similarly to rinderpest virus (RPV). However, our investigations using intranasal inoculation of a recombinant PPRV containing Green Fluorescent Protein (GFP) indicate this is not the case. The PPRV-GFP virus is made from a synthetic cDNA copy of virus obtained from field isolates (PPRV/Mor-08), which produces virus when introduced into cells. GFP emits green light when stimulated by ultraviolet light and so can be visualized using florescence microscopy. Infection with the recombinant PPRV-GFP virus shows that immune cells in the pharyngeal tonsil are the primary target for infection, not epithelial cells. This is a ground-breaking discovery which changes our understanding of PPR pathogenesis. The research was funded by a Farmed Animal Disease and Health (FADH) grant joint funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Indian Government's Department of Biotechnology (DBT) and ISP Virus and ISP CCG for animal experiments. 3. Collaborating with TANUVAS, our Indian collaborators, for the first time we showed that host RNAseq data reveals of the contribution of interferon stimulated genes to the increased host defence and decreased viral replication of PPRV in Cattle. |
| Exploitation Route | Licencing to commercial companies for commercialisation of vaccines. Early events of pathogeneis for PPRV will show the pathogenesis events for other morbillivirus which is not very clear yet. |
| Sectors | Agriculture, Food and Drink,Education,Government, Democracy and Justice,Manufacturing, including Industrial Biotechology |
| URL | https://www.pirbright.ac.uk/news/2020/05/host-defence-genes-may-contribute-peste-des-petits-ruminants-susceptibility |
| Description | Development of DIVA vaccines attracted vaccine producers and funding agencies for signing non-exclusive licencing agreements for commercialising the DIVA vaccines and DIVA tests. GALVMED through gates foundation has recently funded to test the stability of PPR vaccine in the field of Jordan. DIVA vaccines developments, early events of pathogenesis of PPR virus and PPR disease susceptibility have brought many lead/key note invitation Globally. Talks were given at PPR GREN, FAO/OIE forum, vaccine producers meeting, VIROCON and IAVMI meeting in India and many other international conferences in Bangkok, Kenya and Germany. |
| Sector | Agriculture, Food and Drink,Communities and Social Services/Policy,Education,Government, Democracy and Justice,Manufacturing, including Industrial Biotechology |
| Impact Types | Societal,Economic,Policy & public services |
| Description | Development and Evaluation of PPR DIVA vaccines |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Citation in other policy documents |
| Impact | Peste des petits ruminants (PPR) is a highly contagious disease, severely affects small ruminants in almost 70 countries in Africa, the Middle East and parts of Asia. It causes USD 1.5 to 2 billion in losses each year in regions that are home to over 80% of the world's sheep and goats and to more than 330 million of the world's poorest people, many of whom depend on them for their livelihoods. The estimated current expenditure on PPR vaccination ranges between USD 270 and 380 million. The annual impact of PPR alone may be valued at between USD 1.45 and 2.1 billion per year. Approximately a third of the global financial burden of PPR is borne by Africa, with a further quarter borne by South Asia. This burden will be removed with the successful eradication of PPR. The undiscounted costs for a fifteen-year Global control Strategy of FAO and OIE are between USD 7.6 and 9.1 billion, with the first five years costing between USD 2.5 and 3.1 billion. (http://www.fao.org/3/a-i4460e.pdf). PPR is currently controlled by vaccination using mainly two live attenuated PPRV vaccines (Nigeria 75/1 and Sungri 96). However, the current vaccines and serological tests are unable to enable Differentiation between naturally Infected and Vaccinated Animals (DIVA). This factor precludes meaningful assessment of vaccine coverage and epidemiological surveillance based on serology, in turn reducing the efficiency of control programmes. Therefore, it is almost impossible to assess the quality and efficacy of existing PPR vaccines without knowing whether positive animals are vaccinated or naturally infected. Unlike rinderpest, where cattle and buffalo were primary hosts, in PPR, new crops (about 30-40%) of lambs and kids are produced every year and are the most susceptible population to bring back new PPR outbreaks6&7. Therefore, it is likely that the cycle of vaccinations and PPR outbreaks will continue until and unless we reach the stage of 80-90% herd immunity. Therefore, development of a marker vaccine and associated DIVA diagnostics will enable the assessment of vaccine efficacy which is essential for any successful vaccination campaign. https://www.pirbright.ac.uk/news/2018/09/pirbright-scientists-run-vaccination-campaign-eradicate-peste-des-petits-ruminant The availability of a recombinant PPRV vaccine with a proven functionality is a prerequisite for the development of novel vaccines that may enable the development of DIVA tools for PPRV diagnostics. In the DBT-BBSRC FADH BB/L004801/1 grant we have rescued Sungri 96 and Nigeria 75/1 vaccine strains. Both the vaccine strains were rescued from respective synthetic c-DNA clones with mutations in the variable part of C terminus of the nucleocapsid (N) gene similar to Dolphin Morbillivirus (DMV) to enable negative marker DIVA vaccines. These two DIVA vaccines along with parental vaccines have been recently tested in a pilot studies in goats. Both the DIVA and parent vaccines provided safety, stability and protection for vaccinated goats whereas the control animals were clinically infected. Patent applications have been made to protect these DIVA vaccines. Agreements are being done with vaccine industries for the licensing and commercialisation. |
| URL | https://www.pirbright.ac.uk/press-releases/2018/09/pirbright-collaboration-provides-tools-peste-des-... |
| Description | FAO has published a press release on the progress of PPR eradication using vaccines |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Contribution to a national consultation/review |
| URL | http://www.fao.org/news/story/en/item/1367789 |
| Description | Facilitated the transfer of molecular technology for the capacity building of the Sokoine University of Agriculture (SUA) Southern African Centre for Infectious Disease Surveillance (SACIDS) peste des petits ruminants (PPR) laboratory.19-25.01.2020 |
| Geographic Reach | Africa |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | Facilitated the transfer of molecular technology for the capacity building of the Sokoine University of Agriculture (SUA) Southern African Centre for Infectious Disease Surveillance (SACIDS) peste des petits ruminants (PPR) laboratory.19-25.01.2020. The PPR virus infected samples can be diagnosed now at SUA, Tanzania without sending to Pirbright or CIRAD reference laboratories. This will enhance the capacity building of SUA and help immensely in the ongoing PPR eradication. |
| Description | PPR DIVA Vaccine development . FAO/OIE in the meeting proceedings in December, 2018 recorded the future use of DIVA vaccine in the ongoing PPR eradication programme. This will be useful at least at the end phase of eradication to differentiate between vaccination and infection.As such few industries have contacted us to have the DIVA vaccine strains for commercialisation. Also some of the endemic countries are keen to have the strain for testing the DIVA vaccines in endemic settings. |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
| Description | Evalution of a stable liquid formulation of the PPR vaccine in sheep and goats |
| Amount | £225,638 (GBP) |
| Funding ID | IAH-R67A1151A1 |
| Organisation | GALVmed |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 02/2020 |
| End | 07/2021 |
| Description | GCRF Foundation Award |
| Amount | £564,621 (GBP) |
| Funding ID | BB/P023002/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 05/2018 |
| End | 05/2019 |
| Description | Investigating the feasibility of adapting a direct PCR diagnostics approach to in-field animal testing |
| Amount | £864,356 (GBP) |
| Funding ID | 104623 |
| Organisation | Innovate UK |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2018 |
| End | 04/2020 |
| Description | Next generation peste-des-petits ruminats (PPR) vaccines that differentiate between infected and vaccinated animals (DIVA) - proof of concept in sheep |
| Amount | £158,845 (GBP) |
| Funding ID | BB/T004096/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2020 |
| End | 03/2021 |
| Title | Facilitated the transfer of molecular technology for the capacity building of the Sokoine University of Agriculture (SUA) Southern African Centre for Infectious Disease Surveillance (SACIDS) peste des petits ruminants (PPR) laboratory. |
| Description | Facilitated the transfer of molecular technology for the capacity building of the Sokoine University of Agriculture (SUA) Southern African Centre for Infectious Disease Surveillance (SACIDS) peste des petits ruminants (PPR) laboratory. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | This has increased the capability of detection PPRV from infected samples by qPCR at SACIDS, Tanzania. This will be helpful to analyse samples from all over Africa without sending to Europe. |
| Title | Use of reverse genetics to develop PPR DIVA vaccines |
| Description | Reverse genetics technique has been established for PPR virus in our laboratory. As PPR vaccine is a live attenuated virus, it is not possible to differentiate between vaccinated and infected animals (DIVA) in existing antibody assays. However using reverse genetics technique we have manipulated/mutated residues in the full-length cDNA of virus and rescued the live attenuated vaccine strain which worked as a DIVA vaccine. Using this technique a GFP ( Green fluorescent protein) has been introduced into the virulent PPR virus that helped to follow the virus in the infected goats. Similarly using this technique we have modified the existing live attenuated viruses ( Nigeria 75/1) and Sungri 96/1) in to recombinant marker vaccines that enables to differentiate between infection and vaccination ( DIVA). So we have demonstrated that reverse genetics tool can be used to study the pathogenesis and to develop the marker vaccines. This technique can be adapted for other negative strand viruses to design the DIVA vaccines. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | PPR DIVA vaccine developed that can differentiate between vaccinated and infected animals. This will be helpful to know the efficacy of vaccine by knowing the presence antibodies in animal is due to vaccination or infection. This will reduce the eradication time and will facilitate to declare freedom of diseases as soon as Possible without long waiting period. |
| Description | IVRI, Mukteswar |
| Organisation | Indian Veterinary Research Institute |
| Country | India |
| Sector | Public |
| PI Contribution | 1. DIVA vaccine and DIVA test development. 2.Early pathogenesis study for PPR.3. Sharing of Knowledge 4.Joint publications |
| Collaborator Contribution | Development LAMP technique for PPR |
| Impact | 1. Development of DIVA vaccines and DIVA tests 2. Early pathogenesis study showed that PPR virus first replicates in Tonsils 3. LAM assay developed for PPR |
| Start Year | 2014 |
| Description | Indian Veterinary Research Institute (IVRI), Bareilly |
| Organisation | Indian Veterinary Research Institute |
| Country | India |
| Sector | Public |
| PI Contribution | 1. Development of PPR DIVA vaccine and DIVA tests 2. Early pathogenesis study |
| Collaborator Contribution | Development of Biosensor diagnostic assay for PPR |
| Impact | Joint publications. Sharing of knowledge. |
| Start Year | 2014 |
| Description | NIAB, Hyderabad |
| Organisation | National Institute of Animal Biotechnology |
| Country | India |
| Sector | Public |
| PI Contribution | DIVA vaccine and DIVA tests |
| Collaborator Contribution | SNP study for disease resistance |
| Impact | Development of DIVA vaccine and DIVA tests for PPR |
| Start Year | 2014 |
| Description | TANUVAS, INdia |
| Organisation | Tamil Nadu Veterinary and Animal Sciences University |
| Country | India |
| Sector | Academic/University |
| PI Contribution | 1. Development of DIVA vaccine and DIVA test. 2. Early pathogenesis study.3 Contributed to Transcriptome analysis carried out by TANUVAS |
| Collaborator Contribution | Transcriptome study for disease resistance in different breed of goats, sheep and large ruminants |
| Impact | 1.Development of DIVA vaccine.2. Development of DIVA tests 3. Early pathogenesis study showed that Virus first replicate in tonsils.4. High basal level of SLAM is present in large ruminants in comparison to small ruminants and may be therefore large ruminants are more resistant to the PPR. |
| Start Year | 2014 |
| Title | PPR DIVA vaccine |
| Description | We ahve developed two PPR live attenuated DIVA vaccines that can differentiate between vaccinated and infected animals. |
| IP Reference | PCT/GB2019/053641,WO2020128496 |
| Protection | Patent application published |
| Year Protection Granted | 2020 |
| Licensed | Commercial In Confidence |
| Impact | Till date there is no PPR vaccine avalable that can differentiate between vaccination and infection. This causes a huge issue on eradication of the didease and declare freedom from the disease. Therefore our newly develped chimeric live attenauted PPR vaccine and DIVA tests can differentiate between vaccination and infection which is a great achievement for ongoing PPR eradication. Please see detail from the below web. https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2020128496 |
| Title | PPR DIVA vaccines and DIVA tests |
| Description | In a DBT-BBSRC FADH grant, The Pirbright Institute in collaboration with four Indian partners (TANUVAS, IVRI, NIAB and NIVEDI) has developed a PPR vaccine, which will be the first to differentiate between infected and vaccinated animals (DIVA), for which a patent application has been filed. Scientists have manipulated in the genome of PPR full length cDNA and rescued the DIVA vaccine virus using reverse genetic technique. Further this vaccine has been tested in goats providing full safety and potency upon virulent virus challenge. In contrast to current vaccine, this new DIVA vaccine can differentiate between naturally infected and vaccinated animals, therefore will help in meaningful assessment of vaccine coverage and epidemiological surveillance based on serology, in turn increasing the efficiency of control programmes. Our DIVA PPR vaccine and DIVA tests concept are protected through a priority patent application which the Institute filed on 21 December 2018 (Application Number: 1820983.3). |
| IP Reference | |
| Protection | Copyrighted (e.g. software) |
| Year Protection Granted | 2018 |
| Licensed | No |
| Impact | Our DIVA PPR vaccine concept is protected through a priority patent application which the Institute filed on 21 December 2018 (Application Number: 1820983.3). Interest from Vaccine industries and Diagnostics are there and agreements are underway for licencing. |
| Description | Annual project meeting FADH PPR project at IVRI India- February 2018 |
| 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 | The 3rd Annual project meeting for FADH project was carried forward at IVRI between project partners. The work progress has been discussed and further meetings at TANUVAS, India and Pirbright, UK are planned. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Delivered a lead talk at Indian Association of Vetrinary Microbiology and Immunology ( IAVMI) at IVRI, Bareilly on PPR and FMD control by vaccination- February 6-7th, 2020 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Delivered a lead talk at Indian Association of Vetrinary Microbiology and Immunology ( IAVMI) at IVRI, Bareilly on PPR and FMD control by vaccination- February 6-7th, 2020. Further attended the panel meeting with FMD vaccine producers and FMD scientists at PDFMD and IVRI Bangalore to recommend Govt of India for the future control of FMD. Suggested boosting of the first dose FMDV vaccinated animals which will stimulate the immunity up to the second biannual vaccination to avoid any window for infection. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Delivered a lead talk on FMD vaccine and chaired a scientific session at Indian Veterinary Association at New Delhi ( 25.7.19-28.07.19) |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Delivered a lead talk on FMD vaccine and chaired a scientific session at Indian Veterinary Association at New Delhi ( 25.7.19-28.07.19). |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.indianveterinaryassociation.in/wp-content/uploads/2019/07/... |
| Description | Delivered a talk on PPR DIVA vaccine at EU Epizone meeting in Berlin-25.8.19-28-08.19 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Delivered a talk on PPR DIVA vaccine at EU Epizone meeting in Berlin-25.8.19-28-08.19 |
| Year(s) Of Engagement Activity | 2019 |
| Description | Delivered an invited talk on Epidemiology of PPR at wildlife Arusha, Tanzania - 22.10.10-26.10.19 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | Delivered an invited talk on PPR epidemiology at wildlife Arusha, Tanzania - 22.10.10-26.10.19 |
| Year(s) Of Engagement Activity | 2019 |
| Description | Delivered an online lead Talk at organised by Indian Council of Agriculatural Research ( ICAR) and Indian veterinary research institute (IVRI) on Immunological Agents for Animal Disease management |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Online event. many veterinarians and researchers, policy makers from India and abroad joined the meeting. Prof Parida has talked on PPR DIVA vaccines recently developed for the first time using reverse genetics. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Delivered invited talks at Greece veterinary association |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | Greece veterinary authority invited PI to delivered a talk on PPR threat to Greece from Turkey. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Expert group meeting for PPR eradication at head quarters of WHO, Vienna, Austria, 2018 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | In the FAO/PPR eradication meeting satya has presented work on PPR epidemiology and diagnosis. The talk was designed for the stakeholders and policy make to make aware on important points that are required for eradication of PPR |
| Year(s) Of Engagement Activity | 2018 |
| Description | FAO/OIE PPR vaccine expert Group meeting |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Presentations were made on vaccine development including DIVA and stabilised PPR Vaccine. All the vaccine produced, some of the funding agencies including GALVMED, policy makers OIE and FAO have attended this meeting. The meeting was organised by FAO.PI Satya Parida had presented work on Development of DIVA vaccine for PPR and DIVA ELISAs which was appreciated by everybody. In proceedings the use of DIVA vaccines at the end phase of eradication has been encouraged. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Faculty talk at IVRI, India in PPR DIVA vaccine and DIVA tests development |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | Satya Parida delivered an invited talk on PPR DIVA vaccine development using reverse genetics technique. Scientists and post graduate students were enjoyed the talk which sparked many questions and discussions afterwards and the joint Director of IVRI expressed interest on the work and further meetings. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Inception meeting for a Global Challenges Research Fund (GCRF) Global Research Translation Awards, 12.11.2019 |
| 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 | Inception meeting for a Global Challenges Research Fund (GCRF) Global Research Translation Awards, 12.11.2019 |
| Year(s) Of Engagement Activity | 2019 |
| Description | Initiation of a mass vaccination campain ( 2018) in TamilNadu, India |
| 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 | Scientists from The Pirbright Institute's Vaccine Differentiation group have recently returned from Chennai in India, where they conducted a mass peste des petits ruminants (PPR) vaccination campaign and awareness programme. They joined scientists from four specialist organisations; Tamil Nadu Veterinary and Animal Sciences University (TANUVAS), Indian Veterinary Research Institute (IVRI), National Institute of Animal Biotechnology (NIAB) and National Institute of Veterinary Epidemiology and Disease Informatics (NIVEDI). Peste des petits ruminants (PPR), also known as goat plague, is highly contagious and infects small ruminants such as sheep and goats, causing up to 90% mortality. The disease is prevalent across large parts of Africa, the Middle East, India and China and is estimated to cost between US$1.4 billion and US$2.1 billion globally each year. In 2017, the Food and Agricultural Organization (FAO) and the World Organisation for Animal Health (OIE) introduced a global eradication programme to reduce the devastating impact PPR has on the economy and food security of affected countries. "Over 40 vets joined our vaccination campaign in the Tanir Kulum village of Tiruvallur District, TaminNadu (close to Chennai), where we administered vaccines to over 400 sheep and goats in a single day. We also ran an awareness camp where we provided farmers and vets alike with expert guidance on diagnosing clinical signs of PPR and what measures they could take to reduce its spread", said Professor Satya Parida from Pirbright, who led the collaborative effort with Dr Dhinakar Raj from TANUVAS. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.pirbright.ac.uk/news/2018/09/pirbright-scientists-run-vaccination-campaign-eradicate-pes... |
| Description | Invited as PPR vaccine expert to vaccine producers meeting at Jordan, Amman-organised by OIE and FAO PPR secretariat-13.04.19-17.4.19, |
| 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 | Invited as PPR vaccine expert to vaccine producers meeting at Jordan, Amman-organised by OIE and FAO PPR secretariat-13.04.19-17.4.19, |
| Year(s) Of Engagement Activity | 2019 |
| Description | Invited talk at Agricultural Science congress at New Delhi, India, February-2019- Use of reverse genetics to study the early pathogenesis and to develop marker vaccines for PPR |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | 1. In a DBT-BBSRC FADH grant, The Pirbright Institute in collaboration with four Indian partners (TANUVAS, IVRI, NIAB and NIVEDI) has developed a PPR vaccine, which will be the first to differentiate between infected and vaccinated animals (DIVA), for which a patent application has been filed. Scientists have manipulated in the genome of PPR full length cDNA and rescued the DIVA vaccine virus using reverse genetic technique. Further this vaccine has been tested in goats providing full safety and potency upon virulent virus challenge. In contrast to current vaccine, this new DIVA vaccine can differentiate between naturally infected and vaccinated animals, therefore will help in meaningful assessment of vaccine coverage and epidemiological surveillance based on serology, in turn increasing the efficiency of control programmes. 2. Little is known about the early events in the development of peste des petits ruminants (PPR) virus (PPRV) infection. The current dogma is that similar to RPV, PPRV replicates primarily in the epithelium of the respiratory tract before disseminating throughout the host. However, our investigations, using intranasal inoculation of PPRV containing GFP (Green Fluorescent Protein) to mimic natural infection, indicate this is not the case and that immune cells in the pharyngeal tonsil is the primary target. This is a ground breaking discovery which changes the PPR pathogenesis. This infectious GFP virus is made from a synthetic cDNA of field virus (PPRV/Mor-08) using reverse genetics technique under FADH grant. The presentation sparked questions and discussions after the talk. Two PPR DIVA vaccines developed and the mechanism of PPR virus pathogenesis explained. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Invited talk on Epidemiology and vaccine development using reverse genetics techniques at Institute of Life science, Bhubaneswar India. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | Invited talk on Epidemiology and vaccine development using reverse genetics techniques at Institute of Life science, Bhubaneswar India delivered on 5th of Feb, 2018. Students and scientists were encouraged to take forward the approach for human disease and some request obtained to visit our lab at the Pirbright, Institute. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Joined as a FAO expert at Chiang Mai, Thailand for PPR and FMD control in SAARC region and delivered two invited talks- 16.06.19-23.06.19 |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Joined as a FAO expert at Chiang Mai, Thailand for PPR and FMD control in SAARC region and delivered two invited talks on FMD and PPR Global situations- 16.06.19-23.06.19 |
| Year(s) Of Engagement Activity | 2019 |
| Description | Oral and poster presentation at European Society of veterinary Virology and EPIZONE (ESVV/EPIZONE) at Vienna, Austria 2018 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Presentation has been made on early events of PPR virus pathogenesis. The presentation reveled that PPR virus first taken up by the immune cells to the Pharyngeal tonsil and then to other lymph nodes before generalisation of the disease. Secondary replication happens in epithelial cells. This alters the existing believe that virus primarily replicate in the epithelial cells. Similarly a poster presentation has been done to show the detection of nucleic acid of PPR virus during PPR eradication programme, nasal sample has been shown as the best sample for viral genome detection. |
| Year(s) Of Engagement Activity | 2018 |
| Description | PPR eradication meeting organised by FAO and OIE at Rome and talk has been delived on Development of DIVA vaccines |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Satya Parida is working as an expert to PPR eradication and he is being invited for few of FAO/OIE meetings. The meetings discussed about roadmap, vaccine production capacity and eradication policy. Satya also presented work on PPR DIVA vaccine and DIVA tests developments and their evaluation in goats. |
| Year(s) Of Engagement Activity | 2018 |
| Description | PPR vaccine producers meeting at MCI, Morocco organised by FAO/OIE |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | PPR vaccine producers meeting at MCI, Morocco organised by FAO/OIE. Almost all PPR vaccine producers through out world joined this meeting. Satya Parida has presented a talk on vaccine development and transmission of PPR virus in North Africa. There was hues interest on the talk particularly the spread of PPR in North Africa and new vaccine development. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Poster presentation by PhD student and seior postdoc at SGM meeting and Negative Strand Virus (NSV) meeting |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | The work on early events on Pathogenesis of PPR virus has been presented that showed PPR virus primarily replicates in Tonsils, not in the mucosal epithelium as thought till date. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Project close meeting at TANUVAS, Chennai July 2018- Delivering talk on outcome of the project |
| 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 | The project team held their final workshop at TANUVAS, which concluded a four year Farmed Animal Disease and Health (FADH) grant joint funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Indian Government's Department of Biotechnology (DBT). "This grant has enabled us to collaborate with four organisations across India, and ensured that our research can be applied in the field to aid the campaign for PPR global eradication", said Professor Parida.The project covered many areas of research which are essential for understanding PPR and creating tools to help control and prevent the disease. The team have now filed a patent application for their newly developed PPR vaccine, which is the first to differentiate between vaccinated and infected animals (DIVA) - a quality that enables livestock owners to protect their animals whilst continuing to trade. The team have also investigated how the PPR virus (PPRV) infects sheep and goats and how their immune systems respond. By inserting green fluorescent protein into virulent PPRV and administering the modified virus to goats, they demonstrated that PPRV primarily infects the tonsils, challenging the earlier belief that the virus first replicates in the respiratory tract epithelial cells. The collaborative project has also generated better diagnostic tests for use in the field and laboratory, and preliminary research has identified why some Indian breeds of goats and sheep are resistant to the disease, which could help scientists to create PPRV resistant breeds in the future. Project partners, scientists from the University and 40 field veterinarians have joined the meeting. An awareness training has been conducted on PPR disease and eradication for these field veterinarians. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.pirbright.ac.uk/news/2018/09/pirbright-scientists-run-vaccination-campaign-eradicate-pes... |
| Description | The peste des petits ruminants virus (PPRV) Global Research and Expertise Network (GREN) meeting. Presented work on the future eradication of PPRV, 13-15.11.2019 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | The peste des petits ruminants virus (PPRV) Global Research and Expertise Network (GREN) meeting. Presented work on the future eradication of PPRV, 13-15.11.2019 |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://rr-asia.oie.int/wp-content/uploads/2020/06/200622_ppr-gren-2-nairobi-november-2019-final-com... |
| Description | Workshop on PPR at NIAB, Hyderabad India |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Study participants or study members |
| Results and Impact | Project partners delivered talks on PPR diagnosis, Vaccine and genetic resistance. |
| Year(s) Of Engagement Activity | 2017 |