Differentiation of Infection in Vaccinated Animals for PPR and FMD

Lead Research Organisation: The Pirbright Institute
Department Name: UNLISTED

Abstract

Peste des petits ruminants (PPR) is an acute, highly contagious viral disease in sheep and goats. South Asia, Middle East including Turkey and African countries including Morocco are endemic for PPR. The main strategy for disease control is vaccinating sheep and goats with live attenuated PPRV. However there are no DIVA vaccines currently available, preventing the differentiation of infection in vaccinated animals (DIVA) and seromonitoring. FMD is another acute and infectious disease of cloven-hoofed domestic animals for which DIVA vaccines would be of value. Recently we have developed two viral vectored based recombinant FMD DIVA candidate vaccines and the immunogenicity of these vaccines needs to be determined.As wild-type PPRV induces immunosuppression in sheep and goats, we need to determine if the live attenuated PPRV vaccine also induces immunosuppression as this could be a problem if PPRV is used as a vector to deliver multivalent vaccines, or if it is administered with other vaccines. If the vaccine strain does induce transient immunosuppression, further studies are needed to increase understanding of the mechanism of immunosuppression &/or to analyse the immunosuppressive effects.

Publications

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Banyard AC (2014) Peste des petits ruminants virus, eastern Asia. in Emerging infectious diseases

 
Description 1. Two viral vector based FMD vaccines were developed that expressed FMD empty capsids and successfully tested in cattle as pilot studies. The vaccines provide full protection against virulent virus challenge. 2. Two PPR live attenuated DIVA vaccines were produced and tested in goats that provided full protection and could differentiate between vaccination and infection. 3. Inclusion of TLR adjuvants in FMD vaccine will stimulate longer duration immunity. 4. IgA antibody test will detect the current/persistent FMD infection.
Exploitation Route These vaccines and DIVA tests are needed to be tested in larger scale. Currents a patent file has been filed from the Institute. Commercialisation agreements are in progress with vaccine industries.
Sectors Agriculture, Food and Drink,Education,Manufacturing, including Industrial Biotechology

 
Description There is potential for PPR DIVA commercialisation of these vaccines and negotiations are initiated. DIVA tests for FMD and PPR are used to differentiate between vaccinated and infected animals. Inclusion of TLR adjuvants in FMD vaccine will stimulate longer duration immunity. IgA antibody test will detect the current/persistent infection and IDVET is negotiating with the Institute to commercialise the assay.
First Year Of Impact 2012
Sector Agriculture, Food and Drink,Education,Manufacturing, including Industrial Biotechology
Impact Types Policy & public services

 
Description Improvement on FMD and PPR vaccines. Through this partnering award we were able to achive further DBT-BBSRC FADH grant and BBSRC follow on grants whicvh helped us to improve the existing FMD and PPR vaccine. We have now demonstrated that adding TLR adjuvants to the existing vaccine the duration of immunity can be increased upto 6 months. Similarly we have develped PPR DIVA vaccine which can differentiate between infection and vaccination. The Indian Natioanl Goverment and industries are aware of this development so as other through recent FAO/OIE PPR meetings.
Geographic Reach Multiple continents/international 
Policy Influence Type Gave evidence to a government review
 
Description Longer duration immunity for FMD vaccine with TLR adjuvant-Conducted screening of 8 adjuvants with FMD vaccine in cattle and analyse the samples originated from the experiments. 4 selected adjuvants were tested in cattle at the Pirbright Institute and TLR III adjuvant was found as the best one. Under Follow on grant 12 cattle were vaccinated with existing vaccine with oil adjuvant and 12 cattle were vaccinated with oil and TLR III adjuvants. The protective immununity was assessed from the virus neutralizing antibody status. By 6 months post-vaccination only 17% of cattle were having protective antibodies (1:45 dilution) in conventional vaccine group whereas 80% cattle were having protective neutralizing titer (1:45) in TLR adjuvanted group. Therefore it is clear that adding TLR adjuvant one can increase the duration of immunity up to 6 months.
Geographic Reach Multiple continents/international 
Policy Influence Type Gave evidence to a government review
 
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 Right FMD vaccine strains for East Africa. We have shown that existing serotype A vaccine is not working for East Africa where as better serotype O vaccines are availabe internationally for use. Government of all the East afican countries are aware about this from our publications. Further hot spots of FMD virus circulation in tanzania has been identifies through a PhD student collaborating to Glasgow University. We have shown that comination of existing oil adjuvant with TLR adjuvants provides better protection.
Geographic Reach Africa 
Policy Influence Type Gave evidence to a government review
URL https://www.pirbright.ac.uk/press-releases/2017/04/bbsrc-investment
 
Description An effective vaccination programme for the eradication of foot-and-mouth disease from India
Amount £673,500 (GBP)
Funding ID BB/L004828/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 11/2014 
End 02/2018
 
Description FADH PPR project -Understanding the immune mechanism of host disease resistance and development of marker vaccines and DIVA tests for Peste des Petits Ruminants (PPR)
Amount £351,000 (GBP)
Funding ID BB/L004801/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2014 
End 07/2018
 
Description Improving the duration of immunity for FMD vaccine
Amount £201,000 (GBP)
Funding ID BB/N012682/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 05/2016 
End 05/2017
 
Title Appropriate FMD vaccine strains for East Africa and South East Asia and new adjuvants for FMD vaccines that provide longer duration immunity 
Description We have identifies appropriate Vaccine strains for Serotyoe O and A for East Africa and for South east Asia which are published now. Additionally we have identified potent and safe adjuvants which has been tested in cattle and provides longer duration immunity. 
Type Of Material Improvements to research infrastructure 
Year Produced 2014 
Provided To Others? Yes  
Impact Governments of East Africa and Regional OIE centre at South East Asia and vaccine producers are aware about the strains and adjuvants. 
 
Title Benifit of addition of TLR III to existing FMD vaccine 
Description We have demonstrated that TLR III adjuvants along with existing oil adjuvants provides longer duration immunity. 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? No  
Impact This will fulfill the lacuna of short living immunity of FMD inactivated vaccines 
 
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 Adjuvants study-FMD vaccine at Indian Immunologicals 
Organisation Indian Immunologicals Ltd
Country India 
Sector Private 
PI Contribution Conducted screening of 8 adjuvants with FMD vaccine in cattle and analyse the samples originated from the experiments. 4 selected adjuvants were tested in cattle at the Pirbright Institute and TLR III adjuvant was found as the best one. Under Follow on grant 12 cattle were vaccinated with existing vaccine with oil adjuvant and 12 cattle were vaccinated with oil and TLR III adjuvants. The protective immununity was assessed from the virus neutralizing antibody status. By 6 months post-vaccination only 17% of cattle were having protective antibodies (1:45 dilution) in conventional vaccine group whereas 80% cattle were having protective neutralizing titer (1:45) in TLR adjuvanted group. Therefore it is clear that adding TLR adjuvant one can increase the duration of immunity up to 6 months.
Collaborator Contribution Facilitate the animal experiments at their High containment
Impact Conducted screening of 8 adjuvants with FMD vaccine in cattle and analyse the samples originated from the experiments. 4 selected adjuvants were tested in cattle at the Pirbright Institute and TLR III adjuvant was found as the best one. Under Follow on grant 12 cattle were vaccinated with existing vaccine with oil adjuvant and 12 cattle were vaccinated with oil and TLR III adjuvants. The protective immununity was assessed from the virus neutralizing antibody status. By 6 months post-vaccination only 17% of cattle were having protective antibodies (1:45 dilution) in conventional vaccine group whereas 80% cattle were having protective neutralizing titer (1:45) in TLR adjuvanted group. Therefore it is clear that adding TLR adjuvant one can increase the duration of immunity up to 6 months.
Start Year 2016
 
Description Anihwa Call 1 
Organisation Agricultural Research for Development (CIRAD)
Country France 
Sector Public 
PI Contribution Developed PCR to detect PPR viral genome in faecal samples for experimentally infected animals.
Collaborator Contribution Developed PCR and antigen ELISA to detect PPR viral genome in faecal samples for field animals including wild life.
Impact Please see publications
Start Year 2013
 
Description Anihwa Call 1 
Organisation Friedrich Loeffler Institute
Country Germany 
Sector Public 
PI Contribution 1. Conducted challenge experiments in goats to study pathogenicity. 2. Developed NGS technology to sequence PPR whole genome.
Collaborator Contribution FLI has conducted transmission study between different species ( Goats, pig, camel). For the first time they showed that pigs are clinically infected by PPR virus.
Impact Joint Publications
Start Year 2013
 
Description Epitope prediction for FMD and serosurvey in East Africa 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution 1. Vaccine strain selection for O and A serotype for East Africa. 2. Epitope mapping.3. Analysis of sample collected from Tanzania national parks and domestic animals
Collaborator Contribution 1. Establishing mathematical modelling correlating phenotype to genotype circulating viruses against existing antisera. 2. Sero-survey in wildlife and domesticated animals for epidemiological studies.
Impact 1. Vaccine strains were selected for O and A serotypes for FMD for East Africa. 2. Hotspots were detected for FMD prevalence
Start Year 2016
 
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 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
 
Description Vaccine strain selction 
Organisation Onderstepoort Veterinary Institute
Country South Africa 
Sector Academic/University 
PI Contribution 1. Vaccine strain selection for serotype O and A
Collaborator Contribution Vaccine strain selection for serotype SAT1 and SAT2
Impact Vaccine strain for FMD serotype O and A were selected.
Start Year 2012
 
Title Development salivary IgA antibody assay for O,A and Asia1 to detect current FMD infection in field 
Description Development salivary IgA antibody assay for O,A and Asia1 to detect current FMD infection in cattle. 
IP Reference  
Protection Protection not required
Year Protection Granted 2015
Licensed No
Impact Development salivary IgA antibody assay for O,A and Asia1 to detect current FMD infection/persistence in cattle.
 
Title Develpment of PPR DIVA Vaccines and DIVA tests 
Description Manipulating the genome live attenuated existing PPR vaccine we have developed DIVA vaccines and DIVA tests for PPR that can differentiate between infection and vaccination. This will facilitate the eradication at least at the last phase of eradication. 
IP Reference  
Protection Copyrighted (e.g. software)
Year Protection Granted 2016
Licensed No
Impact PPR DIVA vaccines can differentiate between infection and vaccination that will facilitate the eradication at least at the last phase of eradication programme.
 
Title NSP and SP FMD antibody tests 
Description We have validated NSP DIVA tests with FMD vaccinated/infected carrier animals and field sample for an industry. The assays are now in market and Institute is receiving royalty for the sale. 
IP Reference  
Protection Protection not required
Year Protection Granted 2015
Licensed Commercial In Confidence
Impact Due to this validation work now at least two international companies are there for sailing FMD diagnostic assay. This facilitate wide distribution of the kits worldwide.
 
Title TLR II adjuvant can stimulate longer duration of immunity for FMD vaccine. 
Description We have shown that TLR II adjuvant when added to the conventional vaccine, it stimulate longer duration immunity, at least up to 6 months. 
IP Reference  
Protection Protection not required
Year Protection Granted 2016
Licensed No
Impact Provision of longer duration immunity up to 6 months will help in biannual vaccination control policy. When vaccine provides less than 6 months immunity in biannual vaccination programme, there is always a window for infection.
 
Description BBSRC Impact case study 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Trainings, workshops and awareness provided on FMD among farmers at Arusha, Tanzania.
Year(s) Of Engagement Activity 2012
URL https://bbsrc.ukri.org/documents/foot-and-mouth-in-africa-pdf/
 
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 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 Invited lead talk and Chairing brain sterming session on FMD vaccine and control at international conference at Hyderabad Organised by NIAB 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact 1.Invited lead talk on Epidemiology of PPR.2. Chairing brain sterming session on FMD vaccine and control at international conference on Infectious animal diseases at Hyderabad Organised by NIAB
Year(s) Of Engagement Activity 2014
 
Description Invited talk on Efficacy FMD vaccine using TLR adjuvants at NVRQS, South Korea 
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 was invited to deliver a talk on FMD vaccine using TLR adjuvants. Since 2010 South Korea is facing FMD outbreak and preparing themselves to prepare their own FMD Vaccine. As we have identified TLR 3 is a good adjuvant for stimulating humoral and cell-mediated response I received sparked questions and discussion afterwards. Recently I have received queries for providing details about the adjuvants so that they can include this adjuvant to their vaccine.
Year(s) Of Engagement Activity 2016
 
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 Invited talk on new generation FMD vaccines at NIAB faculty 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact Delivered an invited talk on new generation FMD vaccines to inform the collaborator how TLR III adjuvant lingers the duration of immunity. The talk initiated sparking questions after the talk.
Year(s) Of Engagement Activity 2017
 
Description Invited talk to deliver at SEOC ( Spanish Vaterinary Society) and small ruminant research forum, Spain on threat of PPR to Euorope 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Due to recent spread of PPR in north Africa there is a threat of PPR to Europe. A clear discussion was made and an manuscript has been published on this talk in small ruminant journal.
Year(s) Of Engagement Activity 2015
 
Description Oral presentation at EUFMD meeting, Burgo, Italy on Longer duration of Immunity of FMD vaccine 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Talk on duration immunity for FMD vaccine and how it can be double by adding a TLR3 adjuvant to the correct vaccine formulation. This sparked questions and discussion afterwards. vaccine industries were keen on this.
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 at EUFMD meeting at Burgo by the senior postc of the PI group on epitope prediction of serotype O FMD virus 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact In this presentation we have shown 3 new epitopes of the FMD virus. An manuscript has been submitted for publication on this.
Year(s) Of Engagement Activity 2018
 
Description Workshop at Hainan province 
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 An workshop was organised by CAHEC at Hainan province and researchers from Pirbright Institute working on various diseases and researchers throughout China working on PPR and related diseases had joined.Talks were delivered by these researchers throughout the day.
Year(s) Of Engagement Activity 2011
 
Description Yearly visit (n=4) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact PI Satya Parida has visited CAHEC in each year during the project tenure and discussed work with colleagues of CAHEC working on PPR. Couple of times senior postdoc from Pirbright laboratory visited CAHEC with PI for exchange of whole genome sequencing technique discussion. Similar visits have been made by CAHEC and LVRI scientists to the Pirbrght Institute.
Year(s) Of Engagement Activity 2012,2013,2014,2015