GCRF establishment of biopharmaceutical and animal vaccine production capacity in Thailand and neighbouring South East Asian countries

Lead Research Organisation: University of Kent
Department Name: Sch of Biosciences

Abstract

This programme aims to establish state of the art facilities and technology for the production of recombinant proteins, especially biopharmaceuticals and bespoke animal vaccines.

Biopharmaceuticals are protein drugs that are used to treat an increasingly wide range of serious diseases, to the extent that half of all new drugs are predicted to be biopharmaceuticals by 2020. They are usually produced in bacterial or animal cells, which makes them difficult to make and far too expensive for the vast majority of patients in developing countries. In Thailand, fewer than 2% of patients have access to anti-cancer biopharmaceuticals that are routinely used in the UK, and which are on the World Health Organisation's list of 'minimum medicine needs for a basic health-care system'. Cancer rates in Thailand are high and rising, so there is a profound need for these medicines.

Animal vaccines are required to combat infections in livestock, which is a growing problem in Thailand and other countries due to the increasing demands of growing populations. Many imported vaccines do not work well because they were raised against strains that are simply too different. Thailand and other developing countries suffer massive losses in livestock every year, with some outbreaks leading to 90% loss rates.

Countries such as Thailand can only address these problems by producing the biopharmaceuticals themselves, at much lower costs, and by formulating vaccines that are matched to circulating viral strains. Progress in both areas requires large scale facilities for recombinant protein production, usually in E. coli or mammalian cells. This is a highly complex area and most developing countries do not have this capacity - hence they need to import the products. To address this problem the Thai government has established a purpose-built National Biopharmaceutical Facility (NBF), built in 2014 and fully equipped for bacterial/ animal cell systems and product formulation. It has also developed a substantial animal vaccine research group.

The UK has world-class expertise in this area of 'bioprocessing' and this project aims to apply this expertise, initially in Thailand and later elsewhere, to develop the NBF into a state of the art facility that can make both biopharmaceuticals and vaccine antigens. The UK team includes experts in every step of the production chain, including design of expression system, expression of proteins at high levels, large scale cultivation, product extraction / purification, and product 'analysis'. The latter area is crucially important; any drugs licensed for human use have to pass extremely stringent quality tests that involve detailed analysis of the final protein product.

During the project a group of the UK applicants will work closely with the Thai team to transfer their capabilities to the Thai centres and build up production capacity. This will be aided by seconding the UK researchers to Thailand for long periods, and visits by the Thai researchers to the UK to learn new approaches. At the same time, others UK and Thai team members will work with government ministries, companies and farms to ensure that the products will be distributed effectively so that they reach end users. Finally, representatives from a range of neighbouring South East Asian countries will be involved in the network meetings so that they are fully aware of the programme's progress and outputs and able to use the information and technology to initiate their own production pipelines.

Planned Impact

The aim of this programme is to enable state of the art capacity and capability for recombinant protein production in Thailand and other South East Asian countries, with a focus on the production of (i) biopharmaceuticals and (ii) veterinary vaccines. The primary beneficiaries will be:

1. The population of Thailand, through the provision of advanced medicines and increased secure food security.
- the programme will result in a pipeline for biopharmaceutical production that is urgently needed in Thailand and neighbouring countries. The research will lead to the large-scale production of protein drugs that are routinely used to treat a number of cancer and autoimmune diseases in high-income countries. Only a small fraction (fewer than 2%) of Thai patients currently have access to these drugs but this project will result in large-scale, cost-effective production systems that will enable much greater patient penetration rates to be attained. Cancer rates, in particular, are very high in Thailand and the availability of these medicines will have a dramatic positive effect on survival rates and life expectancy for patients.
- The programme will also produce veterinary vaccines against major swine viral diseases that cause massive livestock losses. By preventing or minimising such outbreaks, the work will enhance the productivity of the Thai swine industry, provide better nutrition and safeguard jobs for approximately 200,000 households.

2. The populations of neighbouring South East Asian countries, particularly Vietnam, Cambodia, Myanmar, and Lao DPR.
- representatives from these countries will be involved in programme network meetings from the outset in order to disseminate findings at a regional level. Every assistance will be provided in order to assist these countries to start their own production facilities.
- Several Thai companies will be involved in the production, sales and marketing of these new biopharmaceuticals and vaccines, and some of these companies are large multinationals with bases in the countries listed above. This will provide a natural outlet for distribution of new products within the SE Asian region.

3. The UK Bioprocessing and animal vaccine industries and academic communities.
- while the primary impact is intended to be in SE Asia, the programme will bring together highly-rated UK groups in order to develop effective new platforms and processes for the production of these important molecules. The programme will differ from traditional production systems by focusing more intensively on cost, so that the products can be made more cheaply, ensuring that the products benefit more SE Asian end users. It is undoubtable that the establishment of integrated production processes will be of interest to UK companies and academics, who are very likely to adapt elements of the programme for their own uses. The UK houses some of the world's most prominent biopharmaceutical and animal vaccine companies, many of whom already collaborate with one or more of the applicants. The development of new expression, cultivation, downstream processing systems is certain to be of interest to such companies, as are product analysis data on the proteins that the new facilities generate.

Publications

10 25 50
 
Description The grant has resulted in a number of breakthroughs in terms of production of target high value animal vaccines and therapeutic proteins and as we complete the final year of the project we are moving towards commercialisation for some products. The choice of targets was been determined through discussions with stakeholders in Thailand including the Thai Ministry of Public Health and The Health Intervention and Technology Assessment Program (HITAP) which is a semi-autonomous research unit under Thailand's Ministry of Public Health. It is a non-profit organization with responsibility for appraising a wide range of health technologies and programs.

In terms of biopharmaceuticals, we have produced CHO cell lines expressing 3 different medicines (primarily to treat breast and other cancers) as well as a very promising molecule for the treatment of Dengue fever. We have also produced an E. coli strain expressing a biopharmaceutical to treat macular degeneration. Constructs encoding these molecules have been designed and tested at small scale, and transferred to the Thai partners who will now scale up expression. We will now enter discussions with NBF and other companies to plan the commercialisation of the CHO lines.

In terms of animal vaccines, we have designed and tested constructs encoding a series of porcine vaccine candidates. Two of the constructs show high levels of expression and they have been sent to the Thai partners who have tested them and successfully scaled-up production. Work on one of the vaccine candidates has proceeded very rapidly and we have shown that the protein expresses at high levels (over 1 gram/litre culture), and can be purified in a simple single step. The vaccine performs well in cell-based assays and in small animal trials. We are currently conducting efficacy trials in pigs, with the trial results expected in Spring 2022. If the vaccine is shown to be effective in pigs, we will move rapidly to submit for approval by the Thai FDA and firmly establish collaborations for manufacture and distribution of the product. A major Thai company, BiS Group, plans to distribute the first vaccine once approved.

The grant is aimed at capacity building in Thailand, and the Thai partners have shown that they can successfully produce the porcine vaccine on a large scale and now have optimised CHO cell lines to enhance capacity building from production of biopharmaceuticals using mammalian cells. We are working with the relevant ministries in both Thailand and Vietnam to ensure that the molecules can be effectively submitted for regulatory approval once the production processes have been finalised.
Exploitation Route As we enter the final phase of the project, it is clear that several target molecules are being expressed at the required levels. We are building networks with other potential users who can benefit from this technology. Collaborations have been established with a series of groups and companies in Thailand, Malaysia and Vietnam (see list of collaborations) and this is clear progress in terms of capacity building. In general, several core areas of the research are moving from the development phase to a translational phase.
Sectors Agriculture

Food and Drink

Healthcare

Government

Democracy and Justice

Manufacturing

including Industrial Biotechology

Pharmaceuticals and Medical Biotechnology

URL https://research.kent.ac.uk/gcrfbiopharma/
 
Description During the project we have established collaborations and held discussions with a very wide range of stakeholders including major companies (CPF and BIS - see collaborations and partnerships), the Thai National Vaccines Institute, and many others. We have positioned ourselves so that now we are close to reaching our aim of producing the target high-value molecules at scale, they can be successfully submitted for regulatory approval and will have maximal economic and societal impact. We have developed a process for expressing and purifying a key porcine vaccine candidate, well ahead of schedule. Importantly, the team at NBF have scaled up production of the PCV2d vaccine to industrially-relevant levels. This is a major milestone for the project because this demonstration of capacity-building in Thailand was one of the central aims of the project. It affirms the Thai facility's ability produce high-value recombinant proteins for commercial applications, which greatly increases the potential economic and societal impact that our work can have in Thailand. The vaccine is currently undergoing efficacy trials in pigs and we are negotiating with a major Thai company, who plan to manufacture and distribute the vaccine once it has been approved by the Thai FDA. In addition, as part of a new collaboration that has arisen directly from this award, we are working with NIVR, Vietnam, to develop a lateral flow test for African Swine Fever virus (ASFV), which has had a devastating effect on the pig industry in Vietnam and surrounding countries. We are currently generating antibodies the the ASFV antigen that we have produced and will push this part of the project towards commercialisation as rapidly as possible in the next 12-months. We have also made rapid progress in the development of monoclonal antibody drugs. First, we have produced CHO cell lines that express high-profile biopharmaceuticals, and we are considering avenues for their commercialisation, and secondly, in collaboration with a group in Mahidol University we have designed and produced CHO cell lines that express monoclonal antibodies that target Dengue fever virus. These mAbs will be tested for efficacy in mouse infection trials in the coming months. Key technologies used in the UK groups have been successfully transferred to both of the Thai collaborator groups. Five researchers from the Thai groups have carried out secondments at UCL and Kent to learn core techniques. Three of the Thai RAs who received training on this project have moved on to positions in the Thai Biotechnology industry, a clear indicator that we are succeeding in building capacity in industry as well as academia, which is important for ensuring that this project has maximum economic impact through strengthening the biotechnology sector in Thailand.
First Year Of Impact 2020
Sector Agriculture, Food and Drink,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Cultural

Societal

Economic

Policy & public services

 
Description Influence on Institutional attitudes to international research collaborations
Geographic Reach Asia 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Influence on biopharmaceutical policy in Thailand
Geographic Reach Asia 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Influence on vaccine production and purchasing policy in Thailand
Geographic Reach Asia 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Invitation to serve on International Advisory Board of BIOTEC in Thailand
Geographic Reach Asia 
Policy Influence Type Membership of a guideline committee
Impact The PI Prof Robinson has been invited to serve on the International Advisory Board of BIOTEC, one of the two main Thai partners in this project. The aim is to provide expertise on a range of subjects including international grant applications
 
Description Membership of National Biopharma Mission in India
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact Prof Mark Smales and Dan Bracewell (PIs on this project, from Kent and UCL respectively) are now serving on this board, which aims to enhance biopharmaceutical production and delivery in India
 
Description Showcase event at Ministry of Science, Technology and Innovation, Thailand
Geographic Reach Asia 
Policy Influence Type Contribution to a national consultation/review
 
Description Visiting Professorship, University of Malaysia, Sabah
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact The PI on this project, Prof Robinson, has been appointed as Visiting Professor at the University of Malaysia, Sabah, in order to advise on research efforts and grant acquisition
 
Description Development of vaccines for pigeon circoviruses
Amount ฿1,400,000 (THB)
Organisation Charoen Pokphand Group 
Sector Private
Country Thailand
Start 01/2020 
End 12/2021
 
Description Enhancement, Demonstration and Novel Application of Lonza's GS piggyBac Transposon System
Amount £0 (GBP)
Funding ID Industry funded fellowship (value undisclosed) 
Organisation Lonza Group 
Sector Private
Country Global
Start 03/2020 
End 03/2023
 
Description Generation, characterisation and application of SARS-CoV-2 protein antigens for COVID-19 rapid diagnostic purposes in the hospital and community
Amount £418,025 (GBP)
Funding ID BB/V011324/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2020 
End 12/2021
 
Description Royal Society International collaboration Awards
Amount £225,000 (GBP)
Funding ID ICA\R1\191288 
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2020 
End 02/2023
 
Description Royal Society Newton Advanced Fellowship
Amount £74,000 (GBP)
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2018 
End 09/2021
 
Description SECRETERS; A new generation of microbial expression hosts and tools for the production of biotherapeutics and high-value enzymes
Amount £560,000 (GBP)
Funding ID Secreters Innovative Training Network 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 01/2019 
End 12/2023
 
Title Bacterial strains expressing porcine vaccines transferred to Thai collaborators 
Description This GCRF project involves production of new E. coli strains expressing animal vaccines and their transfer to Thai collaborators for scale-up. New E. coli strains expressing candidate porcine vaccines have been developed and transferred to the collaborating Thai groups. The Thai group at NBF has now scaled up production confirming that the production process is viable, and the vaccine is being tested for efficacy in March 2021. 
Type Of Material Cell line 
Year Produced 2018 
Provided To Others? No  
Impact The Thai collaborators can now produce these recombinant proteins at scale - a major capacity building milestone in this project 
 
Title CHO cell lines expressing biopharmaceuticals + transfer to Thailand 
Description This GCRF project involves production of new strains expressing animal vaccines and their transfer to Thai collaborators for scale-up. New Chinese Hamster Ovary cell lines expressing a series of biopharmaceuticals have been developed and transferred to the collaborating Thai groups 
Type Of Material Cell line 
Year Produced 2019 
Provided To Others? No  
Impact Cell lines transferred to Thai groups for scale-up 
 
Title New E. coli strains expressing biopharmaceuticals - transfer to Thailand 
Description This GCRF project involves production of new strains expressing biopharmaceuticals and their transfer to Thai collaborators for scale-up. 2 new E. coli strains expressing biopharmaceuticals have been developed and transferred to the collaborating Thai groups 
Type Of Material Cell line 
Year Produced 2018 
Provided To Others? No  
Impact Thai groups will develop scale-up protocols 
 
Title Generation of datasets on breast cancer epidemiology in Thailand 
Description Two of the consortium PIs working in Thailand, Dr Fatim Lakha and Prof Richard Coker (employed by London School of Hygiene and Tropical Medicine) have compiled data on breast cancer from a number of sources in Thailand, including the NHSO and Cancer registry. the aim is to provide a needs assessment for the project but the report (in preparation) will provide a 10-year description of breast cancer epidemiology which will be a valuable resource in itself. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? No  
Impact Report has now been published: see URL 
URL https://pubmed.ncbi.nlm.nih.gov/33212481/
 
Description BIOTEC 
Organisation National Center for Genetic Engineering and Biotechnology (BIOTEC)
Country Thailand 
Sector Public 
PI Contribution BIOTEC are a partner in the GCRF project who specialise in the field of animal vaccines. They are working with the UK team to develop new vaccines against porcine circoviruses
Collaborator Contribution BIOTEC provides core expertise in the design of vaccines to porcine circovirus strains that affect SE Asia (PCV2d and PCV3). They have designed recombinant protein constructs that that UK team has now produced in order to develop subunit vaccines to circulating strains of PCV2d and PCV3. The PCV2d vaccine has been shown to be successful in cell-based infection assays and is now undergoing tests in pigs. This is a major output from this project.
Impact Progress is ahead of schedule and the efficacy trials with pigs are currently being conducted. If successful we will push for full commercialisation of the vaccine..
Start Year 2017
 
Description Bioscience Animal Health group (BIS) 
Organisation Bioscience Animal Health Group
Country Thailand 
Sector Private 
PI Contribution BIS are one of Thailand's largest distributors of veterinary products including animal vaccines. They are working with our consortium to assist in our porcine vaccine production project.
Collaborator Contribution BIS currently distribute imported vaccines against pig viruses, but are keen to help us produce new vaccines and have offered to market the vaccines when they have been validated. They are planning to market our vaccine once it is approved by the Thai FDA and have offered to fund safety trials in Thailand.
Impact BIS are now heavily involved in the planning of the project and we have agreed that they will have full rights to market the vaccine in Thailand if the efficacy trials are successful
Start Year 2017
 
Description Charoen Pokphand Foods Thailand 
Organisation Charoen Pokphand Group
Country Thailand 
Sector Private 
PI Contribution Our consortium aims to assist the Thai collaborators to design and produce porcine vaccines in Thailand and elsewhere in South East Asia. The project involves working with end users and regulatory agencies to ensure that we produce the right vaccines and to further ensure that they rapidly proceed through the regulatory approval processes.
Collaborator Contribution CPF Thailand are collaborating with our consortium on the launch of porcine vaccines. They are Thailand's largest producer of pork products and own numerous large farms. They will assist with the design and approval of vaccines against porcine viruses during the course of this project. They have close ties with key Government agencies and are in an excellent position to advise on this project.
Impact CPF are continuing to advise on the requirements for regulatory approval in Thailand and Vietnam
Start Year 2018
 
Description Chulalongkorn University 
Organisation Chulalongkorn University
Country Thailand 
Sector Academic/University 
PI Contribution Our project is aimed at capacity building of recombinant protein production in Thailand and other South East Asian countries. We provide expertise in several platforms to our core GCRF-funded partners but are also aiming to develop new collaborations with other academic and industrial partners in the region.
Collaborator Contribution Chulalongkorn University has a prominent Vaccine Research Center that aims to develop a range of new vaccines. Following initial discussions in Bangkok, they have requested a collaboration with our team in order to learn new techniques for protein production in bacterial and mammalian cell platforms. They seconded a PhD student to our laboratory in Kent for 6 months starting in July 2019 and this was highly successful. They are following up this work with a view to publication in 2021.
Impact Collaboration is ongoing
Start Year 2019
 
Description Dr Isabel Lim, University of Malaysia Sarawak 
Organisation University Malaysia Sarawak (UNIMAS)
Country Malaysia 
Sector Academic/University 
PI Contribution Dr Lim is interested in the production of novel anti-cancer products. She is collaborating with the Kent groups to test extracts from various sources for anti-cancer activity
Collaborator Contribution University of Kent has numerous cancer cell lines and will be testing extracts from Dr Lim's groups for bioactivity.
Impact Collaboration just started
Start Year 2018
 
Description Dr Zarina Amin 
Organisation Malaysian University of Sabah
Country Malaysia 
Sector Academic/University 
PI Contribution Dr Zarina Amin is Director of the Biotechnology Research Institute, University of Malaysia Sabah. Her group is now collaborating with the Kent PIs to develop vaccines against fish pathogens.
Collaborator Contribution The Malaysian fish industries (mainly Tilapia and Grouper) suffer huge losses due to bacterial infections. Dr Amin's group has started a collaboration with the Kent groups to produce recombinant subunit vaccines that are expected to be far more effective than the killed whole bacterial formulations that are currently used.
Impact Dr Amin has successfully applied for a Malaysian grant to develop fish vaccines, with Prof Robinson as co-investigator
Start Year 2018
 
Description Huvepharma biopharma 
Organisation Huvepharma
Country Bulgaria 
Sector Private 
PI Contribution Our research team is developing a PCV2d vaccine together with partners. The aim is to produce this vaccine commercially for use in SE Asia and Huvepharma are a collaboration with a view to them possibly being involved in further commercialisation outside SE Asia,
Collaborator Contribution Huvepharma have expressed an interest in production of the vaccine for distribution in Europe and the US.
Impact Collaboration started vert recently
Start Year 2020
 
Description Mahidol University PhD secondment scheme 
Organisation Mahidol University
Country Thailand 
Sector Academic/University 
PI Contribution We are keen to maintain the collaborations built up with Thai centres during this award, and have agreed that several PhD students in our BBSRC 'SoCoBio' Doctoral Training Partnership will undertake their 3-month placements (PIPS) with collaborators in Mahidol University.
Collaborator Contribution Mahidol will host several phD students per year and waive all fees.
Impact Secondment scheme has just started this year
Start Year 2022
 
Description NBF 
Organisation National Biopharmaceutical Facility
Country Thailand 
Sector Public 
PI Contribution National Biopharmaceutical Facility, Thailand. They are a partner in the GCRF project who receive funding. We have developed a collaboration in order to enhance production of high value proteins in Thailand and other SE Asian countries as part of the GCRF project. NBF are developing capacity for CHO cell culture and production of monoclonal antibodies (biopharmaceuticals) with assistance from the Kent and UCL groups, and for production of animal vaccines.
Collaborator Contribution Partners in Imperial College and UCL are also involved in this collaboration
Impact NBF have produced the PCV2d vaccine candidate at large scale following small-scale production at Kent. This is a major milestone in the project and the first demonstration of industrial-scale production of a high-value recombinant protein by this organisation. This was a key aim in the capacity building programme.
Start Year 2017
 
Description National Institute for Veterinary Research (NIVR), Hanoi, Vietnam 
Organisation Veterinary Hospital - National Institute of Veterinary Research, Vietnam
Country Viet Nam 
Sector Hospitals 
PI Contribution NIVR are a unit of the Ministry of Agriculture and they are heavily involved in combatting animal diseases in Vietnam. Their top priority is to combat African Swine Fever (ASF) virus which has devastated pig stocks (2.2 million pigs culled in Vietnam to date). They urgently need simple ASF detection systems and our team is producing recombinant ASF antigens in order to develop a simple immunological test kit for ASF in blood samples.
Collaborator Contribution A PDRA in the Kent group has epxressed an ASF surface protein in E. coli and is in the process of raising antbodies to this protein. The antiserum will be used in a hand-hled test kit (lateral flow device) for screening pigs in Vietnam.
Impact NIVR have been awarded funding to carry out a pilot project with the Kent team, screening 7000-10000 pigs.
Start Year 2019
 
Description National Vaccine Institute, Thailand 
Organisation National Vaccine Institute
Country Thailand 
Sector Public 
PI Contribution Our project is aimed at capacity building of recombinant protein production in Thailand and other South East Asian countries, with a focus on animal vaccines and biopharmaceuticals. We provide expertise in several platforms to our core GCRF-funded partners but are also aiming to develop new collaborations with other academic and industrial partners in the region.
Collaborator Contribution The Thai National Vaccines Institute is a Government funded centre that is responsible for monitoring vaccine use and security in Thailand. We are collaborating with the NVI on a range of issues to ensure that our porcine vaccines are suitable for Thai needs and for assistance on regulatory approval.
Impact Collaboration is ongoing
Start Year 2018
 
Description PhD student internship programme in Thailand 
Organisation King Mongkut University of Technology Thonburi
Country Thailand 
Sector Academic/University 
PI Contribution I am the lead for 'professional internships for PhD students' (PIPS) for the SoCoBio BBSRC Doctoral Training Partnership. Each student is required to undertake a 3-month placement as part of their PhD and I have organised a placement programme for 7 PhD students with our GCRF collaborators in Thailand. This will help to maintain the legacy and effectiveness of the GCRF programme and lead to new UK-Thai collaborations.
Collaborator Contribution As indicated above: UK PhD students will work in Thailand every year for the duration of the DTP, helping to generate new collaborations.
Impact The internship programme started in 2022 with 7 secondments. It is too early to list outputs.
Start Year 2022
 
Description Pongrama Ramasoota 
Organisation Mahidol University
Country Thailand 
Sector Academic/University 
PI Contribution Dr Ramasoota (Mahidol University, Thailand) has developed a monoclonal antibody against Dengue fever that is in efficacy trials in mice. However, yields from their CHO cells are too low for commercialisation (4 mg/litre culture) so our consortium is collaborating with his group to improve productivity and our aim is to reach yields that are 100-1000 times higher.
Collaborator Contribution As stated above: Dr Ramasoota has developed a monoclonal antibody against Dengue fever that is in clinical trials. However, yields from CHO cells are too low for commercialisation so our consortium is collaborating with his group to improve productivity. Prof Mark Smales' group at the University of Kent are CHO cell experts who are working with Dr Ramasoota to produce super-producing cell lines.
Impact A new range of anti-Dengue Monoclonal antibodies have now been produced, at high yield, and these will shortly be tested for efficacy in mice. If these tests are successful the aim will be to engage with companies to initiate clinical trials,
Start Year 2018
 
Description Roslin Institute 
Organisation University of Edinburgh
Department The Roslin Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution We are providing purified samples of PCV2d antigen that have been produced at small scale at Kent.
Collaborator Contribution Prof Opriessnig is carrying our efficacy trials in pigs at Iowa State University (where she holds a joint position).
Impact Prof Tanja Opriessnig (Roslin Institute) is an expert in pig vaccine trials, and is conducting efficacy tests in pigs using our new PCV2d vaccine.
Start Year 2020
 
Description SBS 
Organisation Siam Bioscience Co., Ltd
Country Thailand 
Sector Private 
PI Contribution Provision of new CHO and E. coli strains and analytics expertise
Collaborator Contribution SBS are a Thai biopharmaceutical company who will be a partner in the GCRF project
Impact Collaboration started recently
Start Year 2017
 
Description Sartorius 
Organisation Sartorius
Department Sartorius Stedim Biotech
Country France 
Sector Private 
PI Contribution We are setting up a protein expression facility using the equipment purchased on a BBSRC ALERT grant. Thai and UK appointees on the GCRF grant are receiving training in the use of the equipment.
Collaborator Contribution Sartorius supplied the equipment and are helping to establish a facility; they have also provided consumables as part of a collaborative project on optimising the setup
Impact Collaboration is proceeding smoothly and we have submitted a manuscript for publication that includes authors from Sartorius.
Start Year 2018
 
Description Universiti Putra Malaysia 
Organisation Putra Malaysia University
Department Department of Pathology
Country Malaysia 
Sector Hospitals 
PI Contribution Our project is aimed at capacity building of recombinant protein production in Thailand and other South East Asian countries. We provide expertise in several platforms to our core GCRF-funded partners but are also aiming to develop new collaborations with other academic and industrial partners in the region.
Collaborator Contribution The collaboration is with Dr Maha Abdullah. Her group is interested in identifying and testing vaccines for the aquaculture industry in Malaysia and she has asked for assistance in the expression of a range of target proteins. The Kent group is now expressing these proteins and have sent samples to Dr Abdullah for efficacy trials this year (2021).
Impact Collaboration is entering an important phase. We have sent samples of vaccine candidates that have been purified after expression in E. coli. These will be tested for their ability to protect fish against pathogen attack.
Start Year 2018
 
Description Vanvimon Saksmerprome 
Organisation National Center for Genetic Engineering and Biotechnology (BIOTEC)
Country Thailand 
Sector Public 
PI Contribution Dr Saksmerprome (BIOTEC) is working on vaccines against shrimp viruses. She is working with University of Kent PIs to develop new systems to combat infections and the Robinson group is developing algal strains that express anti-viral RNAs. Algal strains expressing these molecules have been sent to Thailand and are undergoing efficacy trials in shrimp larvae. There is clear evidence that the algal extracts protectr from viral infection and the Thai group are now seeking commercial partners.
Collaborator Contribution The Kent group is developing new methods to produce anti-viral molecules that can be used to prevent viral infections that cause massive losses in the Thai shrimp industry. She is now an 'associate partner' in the GCRF consortium. Dr Saksmerprome has recently been awarded a Newton Advanced Fellowship to work with Prof Robinson's group, significantly strengthening the collaboration. Very recently, Prof Robinson, Dr Saksmerprome and another Thai PI have been awarded a 3-year Royal Society International Collaboration Award to develop an expanded research programme.
Impact The Newton Advanced fellowship (£74,000) and Royal Society ICA (£225k) described above
Start Year 2017
 
Title A method for production of capsid proteins from Porcine Circovirus 2 and Porcine Circovirus 3 in E. coli for vaccine formulations 
Description Patent application describes a new method for the low-cost production of a vaccine against porcine circovirus 2. This was a milestone aim in this GCRF project. Abstract: Effective vaccines are essential to prevent outbreaks and thereby reduce poverty, hunger and economic losses. Porcine circovirus 2 (PCV2) is a devastating pig disease that reduces farrowing and increases death rates in piglets, causing large economic losses worldwide. Porcine circovirus 3 (PCV3) is an emerging disease identified in 2016 that is often found to co-infect with PCV2. Vaccines are available and widely used for PCV2. There are currently no vaccines against PCV3. This invention includes a method for the expression and purification of a chimeric protein that comprises ORF2 proteins from both PCV2d and PCV3 in E. coli. The protein is expressed as a chimera, with ORF2 from PCV2d and PCV3 joined by a synthetic linker. We have developed a scalable single-step purification method, which results in cleavage of the linker between the PCV2d and PCV3 proteins and production of a high titre of PCV2d ORF2 and low levels of PCV3 ORF3. Based on this method, the PCV2d ORF2 protein is purified in large amounts (1-2 g/L) compared to US9717785 B2 (100mg-200 mg/L). The single-step protein purification method used in this invention is low-cost and scalable, so is industrially relevant. The purification method described in US9717785 B2 is not feasible at an industrial scale. The purification method in this invention produces recombinant protein of higher purity than a commercially available subunit vaccine, Porcillis PCV. 
IP Reference Submission number 2001005369. Submitted in Thailand (in Thai) in September 2020 
Protection Patent application published
Year Protection Granted 2020
Licensed No
Impact Submission of the patent application in Thailand will be followed by an application to the Thai FDA for approval to distribute the porcine vaccine in Thailand
 
Title Anti-Dengue virus monoclonal antibodies 
Description Dengue fever is a massive problem in SE Asia and elsewhere and effective treatments are urgently needed. A collaborating group at Mahidol University, Thailand, has developed monoclonal antibodies that are effective at preventing infection in cell based assays. The problem was that yields were far too low for further testing. Prof Mark Smales, a PI on this project, is collaboration with the group and has developed a number of CHO cell lines that express the antibodies at 100x higher levels. These antibodies and cell lines have been shipped to Thailand and efficacy tests are now underway. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Initial development
Year Development Stage Completed 2021
Development Status Under active development/distribution
Impact Project is now underway but it is too soon to judge impacts 
 
Title Porcine Circovirus 2 challenge trials in pigs 
Description Our PCV2 vaccine is being tested in pigs starting in March 2021, in controlled facilities at Iowa State University. If the trials are successful we will seek approval to license in Thailand from the Thai FDA, and will initiate the process of obtaining regulatory approval outside Thailand together with other companies. A major Thai veterinary products company intends to produce and distribute the vaccine once this stage is reached. 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2021
Development Status Under active development/distribution
Clinical Trial? Yes
Impact This is a major milestone in this project. Our aim from the outset was to enable Thailand to produce its own veterinary vaccines (and biopharmaceuticals) and this PCV2 vaccine was designed in Thailand, expressed and purified at small scale in the UK, and then produced at large scale in Thailand. The ultimate aim is for the vaccine to be distributed in SE Asia and we are ahead of schedule in this key element of the programme. 
 
Description 'Think Kent' film on GCRF programme 
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 The University of Kent commissioned a professional 12 minute documentary on the aims and outcomes of this GCRF award (URL below). This was a live broadcast with a Q&A session afterwards. The Thai version of the film is being broadcast in Thailand (in Thai) in March 2021.

https://www.youtube.com/watch?v=gGlzQw_jdvQ
Year(s) Of Engagement Activity 2020
 
Description 4th International Biotechnology and Bioengineering Conference, Kuala Lumpur 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was an international conference on industrial biotechnology, attended by a wide range of academics, companies and stakeholders. I was asked to give a Plenary presentation on our research and our GCRF project
Year(s) Of Engagement Activity 2019
URL https://bioscienceconference.com/biotech-2019/
 
Description Animal Vaccines Workshop, Hanoi, May 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact The consortium organised a workshop on animal vaccines in Hanoi in May 2019, which was attended by researchers and policy makers from Vietnam, Myanmar, Thailand and Taiwan. This workshop allowed multiple new connections to be made outside of Thailand and led directly to a new project working on African Swine Fever with a Vietnamese group at NIVR. Importantly, we developed excellent links with potential industrial partners, including VaBiotech (Vietnam) and CP-Group (Thailand/Vietnam).
Year(s) Of Engagement Activity 2019
URL https://research.kent.ac.uk/gcrfbiopharma/2019/06/08/animal-vaccines-workshop-in-hanoi-leads-to-new-...
 
Description Bangkok GCRF project showcase event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Our GCRF project team held a 'showcase event' In Bangkok on November 28, 2018 and the event was split into two parts:

1. Scientific session for 70-80 people on November 28, 2018, at the Sofitel Bangkok Sukhumvit. The aim was to invite senior research leaders from Thai Universities and companies, together with representatives from elsewhere in SE Asia. The event involved:
- lunch from 12-1
- talks and poster session from 1-5

2. Subsequent evening reception for 130 people at the British Embassy Residence from 7-9, to showcase the network's activities. We invited representatives from numerous government ministries, the Heads of Thai Universities and a range of other stakeholders.
Year(s) Of Engagement Activity 2018
URL https://research.kent.ac.uk/gcrfbiopharma/2018/12/17/gcrf-showcase-event-in-bangkok-brings-together-...
 
Description Bioprocessing Asia, November 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This is a major international conference held in Langkawi, Malaysia, in November 2018. One of the consortium PIs, Prof Dan Bracewell from UCL, is giving a presentation on the consortium's research
Year(s) Of Engagement Activity 2018
URL https://www.bioprocessingasia.net
 
Description GCRF Conference at University of Kent 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact The University of Kent hosted a major GCRF conference in July 2018. It was an opportunity to learn about this significant research fund, but also to meet and work with colleagues to develop projects that would benefit those living and working in ODA-compliant countries.

The programme of the conference is available below.

Programme
The details of the programme are given below for reference. A pdf of the programme is available here. The speakers' biographies are available here. Where available, the speakers' slides are included after the title of their talks.

Monday 2 July: Understanding the context

09:00 Registration
09:30 Opening remarks
09:45 Welcome (Prof Karen Cox, the Vice Chancellor)
10:00 The GCRF and Prioritising the Most Marginalised in the Context of Global Development Challenges (Dr Jaideep Gupte, GCRF Theme Leader, UKRI) (slides - pdf)
10:30 Coffee
11:00 Global Challenges: the view from Parliament (Baroness Suttie)
11:10 The Changing Landscape of International Research Funding: opportunities, challenges and partnerships (Rachael Sara-Kennedy, Universities UK International) (slides - pdf)
11:40 Research Capacity Building in Low and Middle Income Countries (Savita Ayyar, Wellcome/DBT India Alliance, and Allen Muyaama Mukhawana, African Academy of Sciences)
12:15 Lunch
13:15 Key issues facing NGOs
A series of short talks from NGOs
AMREF Africa (slides - pdf),
Care International (slides - pdf),
Doctors with Africa (slides - pdf),
Integrity Action (slides - pdf),
Penal Reform International (slides - pdf),
Toybox (slides - pdf),
World Bicycle Relief (slides - pdf).
14:30 Coffee and networking
15:30-16:00 Optional tours of labs (Engineering and Digital Arts, Biosciences, Physical Sciences) or the campus.
17:00 Buffet and drinks reception
Tuesday 3 July: Developing projects

09:00 Opening remarks
09:15 Internationalisation in higher education (Dr Anthony Manning, Dean of Internationalisation, Kent)
09:30 Challenges and opportunities of leading a GCRF project: lessons learnt
09:30 Prof Elena Korosteleva, Principal Investigator of UKRI COMPASS (slides - pdf)
09:50 Prof Colin Robinson, Principal Investigator of the GCRF project to establish biopharmaceutical and animal vaccine production capacity in Thailand and neighbouring South East Asian countries (slides - pdf)
10:10 Dr Maria Paola Scaparra, Principal Investigator of project to understand how operational research can contribute to the achievement of the UN Sustainable Development Goals (slides - pdf)
10:30 Practical implementation of the 2030 Agenda through localising the Sustainable Development Goals (Dr Carl Wright, Commonwealth Local Government Forum)
11:00 Introduction to the Workshops (Karen Foundling, The Collective (facilitators))
11:10 Coffee
11:30 Facilitated Project Development Workshops
These will help delegates to talk openly about global challenge questions with colleagues form a range of different disciplines. The sessions will become increasingly focussed over the course of the following three and a half days
13:00 Lunch
13:45 Facilitated Project Development Workshops
Following the earlier discussions, the delegates will break into themes.
Human rights, good governance and social justice (provocateur: Harmonie Toros; expert: Elena Korosteleva; facilitator: Sarah Tetley)
Equitable access to sustainable development (provocateur: Rod Westrop (BBSRC); expert: Colin Robinson; facilitator: Helen Leech)
Sustainable economies and societies (provocateurs: John Morton & Adrienne Martin (Natural Resources Institute); expert: Maria Paola Scaparra; facilitator: Michelle Secker)
15:00 Coffee
15:30 Facilitated Project Development Workshops
17:00 Close
Wednesday 4 July: Working on the Detail and Preparing Bids

09:00 Essential Elements of Successful Funding Applications (Phil Ward, Deputy Director of Research Services) (slides - pdf)
lessons learnt by investigators and prioritisation panellists, gathered from a decade of the Grants Factory
09:45 Specific Requirements and Preparation of GCRF Bids (Dr Andrew Massoura, Grants and Contracts Manager) (slides - pdf)
What to watch out for in preparing a GCRF bid, including due diligence and post-award monitoring
10:30 Coffee
11:00 Feedback on Draft Projects
an opportunity for delegates to discuss their ideas and research questions across the three themes.
12:15 Workshops: responding to the feedback
13:00 Working Lunch
13:15 Workshops: examining specific questions
15:00 Coffee
15:30 Workshops: examining specific questions
17:00 Close
Thursday 5 July: Consolidation of the projects

09:00 Facilitated Project Development Workshops
11:00 Coffee
09:15 Facilitated Project Development Workshops
12:30 Lunch
14:00 Visit to Canterbury Cathedral
19:00 Gala dinner
Friday 6 July: Conclusion and next steps

09:00 Opening remarks
09:15 Feedback from breakout groups
10:30 Coffee
11:00 Next Steps: the University's GCRF Strategy (Dr Simon Kerridge, Director of Research Services, Kent)
11:15 Closing remarks (Prof Philippe De Wilde, Deputy Vice Chancellor Research and Innovation, Kent).
Year(s) Of Engagement Activity 2018
URL https://research.kent.ac.uk/researchservices/gcrf2018/
 
Description GCRF IBBEDW Impact Monitoring workshop, London, March 11, 2020 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation by professor Robinson to UKRI GCRF grant holders, on methods of achieving impact in GCRF projects
Year(s) Of Engagement Activity 2020
 
Description GCRF networks vaccinology conference, Bangkok 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact The MRC, BBSRC, EU and WHO are holding an international conference on vaccines in Bangkok in December 2018. The consortium PI, Prof Robinson, has been invited to describe our project aims.
Year(s) Of Engagement Activity 2018
URL https://intvetvaccnet.co.uk/gcrf-networks-vaccinology-course-0
 
Description India Alliance webinar (India) 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact This was an invited webinar from the India Alliance: 'DBT/Wellcome Trust India Alliance (India Alliance) is an independent, dynamic public charity that funds research in health and biomedical sciences in India. India Alliance invests in transformative ideas and supportive research ecosystems to advance discovery and innovation to improve health and well-being. India Alliance encourages diversity, inclusivity, and transparency in science and works to facilitate engagement of science with society'. The aim was to describe the GCRF programme and to advise Indian research groups on how to apply for international funding.
Year(s) Of Engagement Activity 2020
URL https://www.indiaalliance.org/science-communication-workshop
 
Description International Symposium on Human and Veterinary Viruses, Bangkok, 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This internation conference on vaccines was held in Bangkok in February 2018. A consortium members from UCL, Prof Tarit Mukhopadhyay gave a talk that introduced the consortium's aims and research.
Year(s) Of Engagement Activity 2018
 
Description Presentation at International Veterinary Vaccine Network conference, Hanoi, December 2020 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Dr peera Jaru-Ampornpan (PI on this grant) gave an invited presentation at the IVVN network conference 'Vaccines for Swine'
Year(s) Of Engagement Activity 2020
 
Description Stakeholder engagement visit to Hanoi, February 2019 
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 My visit to Hanoi during the week of February 25-March 1 was to develop collaborations with academic and industrial partners and to develop relationships with government ministries. The meetings included:
(i). Meeting with 4 executives from Charoen Pokphand Foods, Vietnam (very large producer of pork goods and hugely influential in Thailand and Vietnam). The aim was to collaborate on our consortium's production of porcine vaccines.
(ii). Presentation at the Vietnam Academy of Science and Technology and initiation of a collaboration with Dr Dang Diem Hong's group.
(iii). Meeting at the British Embassy with Science and Technology experts to start the process of interacting with the Vietnamese Ministries of Agriculture and Science.
Year(s) Of Engagement Activity 2019
 
Description Thailand Research Expo Symposium 2021 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact National Research Council of Thailand (NRCT) holds an annual Thailand Research Expo Symposium and the event in 2021 featured an entire session devoted to this grant's activities.
Year(s) Of Engagement Activity 2021