Protecting pigs and people through collaboration in Southeast Asia

Young piglet receiving vaccination

Collaboration, capacity building and knowledge sharing have supported Thailand’s ability to respond to animal and human health issues.

Biopharmaceuticals are medical products that have been produced or extracted from biological sources, such as:

  • vaccines
  • gene therapies
  • cells
  • tissues.

The global industry continues to grow, and biopharma products have become a crucial component of healthcare systems. A 2018 Nature article estimated that 40% of the 6,000 or more products in clinical development globally were biopharmaceuticals.

Global health inequality

Spending on health and pharmaceuticals in countries in the Organisation for Economic Co-operation and Development continue to significantly outstrip low- and middle-income countries.

Global health inequality results in more out-of-pocket spending and lower life expectancies for lower-income countries.

Biopharmaceuticals are following the same pattern, with those produced in high-income countries not always available or applicable to other areas of the world.

Noncommunicable diseases (NCDs), such as cancer, diabetes and heart disease, are the leading cause of death in Thailand, claiming 400,000 lives per year and making up 74% of total deaths.

NCDs also cost the Thai economy THB 1.6 trillion per year (equivalent to £36.6 billion), 10% of its 2019 GDP.

Communicable diseases, including but not limited to malaria, Dengue fever and tuberculosis, are also major human health issues.

Prosperity and food security

Animal health is also key to prosperity and food security. Pork, chicken, and seafood are the major protein industries in Thailand for production and consumption.

According to the Food and Agriculture Organization (FAO), in 2020, Thailand’s highest production values (tonnes) for livestock products were:

  • chicken meat: 1,782,014
  • whole cow milk: 1,200,000
  • pig meat: 893,500
  • hen eggs: 713,242.

In comparison, cattle meat was measured at only 113,010 tonnes. The fish and seafood industry also provides a massive proportion of Thailand’s protein intake. The FAO also estimates that, in 2019, Thailand produced a total of 2,369,260 tonnes of fish and seafood, including:

  • 565,310 of freshwater fish
  • 564,390 of pelagic fish
  • 435,780 of crustaceans (including shrimp).

That’s nearly on par with Thailand’s 2020 total meat production (2,871,326 tonnes, excluding offal and fat).

Vulnerable to viral infections

Both the pork and seafood industries are farmed intensively, making them vulnerable to viral infections that can cause catastrophic damage to farms. Diseases that target these industries can have a devastating effect on Thailand’s economy and food security.

For example, African Swine fever can have up to a 100% mortality rate in pigs. Similarly, yellow head disease can have up to a 100% mortality rate in tiger prawns.

A programme of inoculations and other therapies that combat these infections could help stabilise production and protect food security.

The UK can use its world-class bioprocessing expertise to collaborate with Thai institutes, maximising opportunities from existing infrastructure and enabling growth in both capacity and capability through knowledge sharing.

About the project

The project was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and Global Challenges Research Fund. It was led by the University of Kent with the support of University College London and Imperial College London.

The project collaborated with Southeast Asian academic, research, and industrial partners to build biopharmaceutical production capacity.

In Thailand, the National Center for Genetic Engineering and Biotechnology (BIOTEC) and King Mongkut’s University of Technology Thonburi (KMUTT) were two key collaborators. This was due to their connection with Thailand’s National Biopharmaceutical Facility (NBF) and their expertise within the biopharmaceutical sector.

Enhancing expertise

Thailand’s NBF began in 2008 via a collaboration between the BIOTEC and KMUTT. A key objective of the project was to enhance the NBF’s expertise in producing molecules for both human and animal health through knowledge exchange and training.

Thailand commissioned the NBF to enable the country to produce biopharmaceuticals, such as antibodies and other proteins. Together with Siam Biosciences, an independent Thai institute, the NBF established a strong base for capacity building.

The UK has a well-established biopharmaceutical industry and community of academics. Through knowledge exchange and training, world-leading UK experts within the field helped build upon the existing infrastructure to fill experience gaps.

International collaborations

The project expanded beyond Thailand, with institutes in Malaysia and Vietnam, targeting needs specific to each location. Face-to-face meetings, country visits and workshops were fundamental in building these international collaborations.

Professor Colin Robinson, the principal investigator and coordinator of the project at the University of Kent, says:

We met as many stakeholders as possible in as short a time as possible.

We held workshops in Bangkok and, to make sure it wasn’t purely Thailand-oriented, our university sponsored a workshop in Hanoi.

We had a showcase event for the whole consortium in the British Embassy that was spectacularly successful, as well as a conference.

So, we met a lot of people and started a lot of collaborations, and some of those have been very valuable.

Visiting UK universities

NBF researchers visited the UK for training at several universities, including:

  • University of Kent
  • University of College London
  • Imperial College London
  • London School of Hygiene and Tropical Medicine.

The training covered the entirety of the production chain, ranging across designing constructs, expressing proteins at high levels, and purifying proteins.

Colin says:

For human biopharmaceuticals, you need to have an excellent capability for analysing the products as you go.

The capacity building couldn’t have happened without the personnel exchanges.

That’s one of the most vitally important outputs of the project, having people trained in those essential techniques.

Collaboration beyond the project

Collaboration between partners for training will also continue beyond the end of the project. Four of the international project partners are listed as associate partners on a new EU Doctoral Training Programme, which will fund 10 early career researchers.

With the BBSRC-funded South Coast Biosciences Doctoral Training Programme, training and knowledge sharing remains an integral method of building upon infrastructure globally.

Once the capacity building was well underway, the team was able to test the NBF’s capability by producing molecules that were well-known and documented.

Collaborators:

  • BBSRC, UK Research and Innovation, UK
  • KMUTT, Thailand
  • NBF, Thailand
  • BIOTEC, Thailand
  • Imperial College London, UK
  • University College London, UK
  • London School of Hygiene and Tropical Medicine, UK
  • Roslin Institute, UK
  • Sartorius, France
  • National Vaccine Institute, Thailand
  • National Institute for Veterinary Research (NIVR), Ministry of Agriculture, Vietnam
  • Bioscience Animal Health, Thailand
  • Huvepharma, Bulgaria
  • Chulalongkorn University, Thailand
  • Charoen Pokphand Foods, Thailand
  • Siam Bioscience Co. Ltd, Thailand
  • Putra Malaysia University
  • Mahidol University, Thailand.

Impacts of the project

Long-term impact through training for talent

The training conducted by the project was a huge success. The NBF and Siam Biosciences have appointed several participating individuals who have new skills in mass-spectrum analysis and downstream processing.

Peera Jaru-Ampornpan, co-investigator of the project at BIOTEC, says:

I think one of the most important long-term impacts is we’re now part of a network for biopharmaceutical production.

Before this, our upstream research lab wouldn’t be involved with downstream factories like the NBF.

This project facilitated those links and enabled us to look at the whole process.

The relationships and network built over the course of the project are a fundamental part of the capacity building, further streamlining future collaborations.

Animal health

Protecting the pork industry through vaccination

The project has made significant progress on a vaccine for a subtype of PCV2, known as PCV2d. The NBF worked together with the University of Kent and the porcine virus group at BIOTEC.

The vaccine has been shown to produce a robust antibody response in rabbits and mice and is currently undergoing animal trials to ensure it’s effective in pigs.

A successful vaccine for PCV2 would result in a reduction in livestock loss and economic damage. This would be particularly vital for rural pig farm owners and farm workers who rely on the industry for employment and economic security.

PCV2 is associated with numerous diseases, collectively referred to as ‘Porcine Circovirus diseases’ (PCVD), with widely ranging symptoms. For example, PCV2-systemic disease (PCV2-SD) can cause heavy weight loss, with a morbidity rate of 5 to 20% in young pigs.

PCV2 is, therefore, an economically important virus and a concern for food security.

Peera says:

We knew that there were successful commercial vaccines available for PCV2, but the technology and methods they use are very expensive.

If we wanted to sell it, it had to be affordable for Thai farmers.

Adapting for a high mutation rate

The primary control method for PCV2 is vaccination. By having a locally produced vaccine, they can continue to adapt to PCV2 with its high mutation rate.

Furthermore, the strains that circulate in Thailand differ from those in the West, so imported vaccines have not always been fully effective.

The project has made significant progress on a vaccine for a subtype of PCV2, known as PCV2d. The NBF worked together with the University of Kent and the porcine virus group at BIOTEC.

BIOTEC found the best DNA sequence, and the antigen was carefully designed through small changes in the genetic code.

The project also needed to find the best production method that didn’t infringe on existing vaccine intellectual properties, using E. coli which is able to produce more of the protein.

If the animal trials are successful, the vaccine can undergo safety trials, be approved by the Thai Food and Drug Administration, and then be commercialised.

Making industry links

The project has already made industry links. A major Thai company, with distribution networks in other Southeast Asian countries, is on board to facilitate the commercialisation of the vaccine.

Charoen Pokphand Foods Thailand, Thailand’s largest producer of pork products, is also involved in the collaboration through sharing ideas and expertise on Thailand’s PCV2 status.

Video credit: University of Kent
On-screen captions and an autogenerated transcript are available on YouTube.

Fast testing for African Swine fever

In addition to the impacts around collaboration, knowledge sharing, and the progress of the PCV2 vaccine production, the project has led to promising potential products across animal and human health.

These products could have significant social and economic impacts for Southeast Asian countries if they successfully bring health benefits.

The University of Kent has collaborated with NIVR in Hanoi, Vietnam, to combat African Swine fever virus (ASFV). The Kent group have produced an ASF antigen in E. coli cells, and the collaboration is working on raising antibodies against it.

The team will be able to use the antibodies to produce a lateral flow test for ASFV, enabling nation-wide testing of pigs. Once successful, the NIVR is ready to conduct a pilot project on 7,000 to 10,000 pigs to see how effective the test is.

ASFV primarily affects pigs and boars, causing fever, reddening of the skin, dysentery, and lack of energy, among other symptoms. Severe strains of the virus can have up to a 100% mortality rate.

COVID-19 equivalent in the pig world

Colin says:

African Swine fever is devastating. It’s the equivalent of COVID-19 in the pig world. It’s incredibly damaging in terms of economic impact.

The problem is that the detection method uses PCR, and low-income regions of Vietnam just do not have access to the equipment or expertise needed to take blood samples and screen them.

The Oxford University group, which specialises in ASFV, is also involved in the collaboration and is sharing control samples from pigs produced by The Pirbright Institute. The Pirbright Institute is strategically funded by the BBSRC. The lateral flow test will also be evaluated using these samples.

Peera says:

Fast detection is the key to containing this disease in farms, especially as ASF can spread rapidly throughout the whole herd.

Using antiviral molecules to shield shrimp against disease

The University of Kent, BIOTEC, and Professor Saul Purton (UCL and Algae-UK) have developed algal strains that can produce specialised RNA molecules.

These molecules could protect against two key viruses for the Thai shrimp industry, Yellow Head Virus (YHV) and White Spots Syndrome Virus (WSSV). They are currently undergoing efficacy trials in Thailand.

YHV and WSSV are both major diseases of concern for Thailand’s aquaculture industry. YHV kills quickly, with up to a 100% mortality rate in three to five days.

WSSV is similarly lethal for shrimp (approximately 80% mortality), also affecting certain crabs, crayfish and lobster species at lower mortality rates. Both diseases have the potential to wipe out the entire shrimp population on a farm.

Colin says:

These viruses can be devastating. Some years they lose 40% of the crop, and it’s a problem elsewhere in Southeast Asia.

The antiviral molecules will be undergoing efficacy trials in 2022 and, if successful, could protect against two diseases that can have dramatic effects on the industry.

Fighting fish diseases with vaccines

The University of Kent is working with the Malaysian University of Sabah to produce more effective vaccines for bacterial infections in fish.

A separate collaboration with the Putra Malaysia University also focuses on vaccine candidates for fish diseases. The University of Kent has expressed the proteins needed for the vaccines, which are undergoing challenge trials in Malaysia in 2022.

Both collaborations are still in their early stages but could prove extremely valuable for Southeast Asian fish industries if effective.

Human health

Anti-cancer biopharmaceuticals

Molecules for cancer therapies are in high demand in Thailand but are also relatively expensive, with less than 2% of patients having access to treatments regularly used in the UK.

The project has successfully expressed three biosimilars in high amounts, including Herceptin. Herceptin, or ‘trastuzumab’, is a monoclonal antibody used to treat HER2+ breast cancer.

The components and analytics have been transferred to Thailand, where they can be used for further training at the NBF.

If commercialised, these biopharmaceuticals can help to address the unavailability of cancer treatments in Thailand. It also illustrates the NBF’s capacity to effectively produce molecules on par with the international community.

Dr Fatim Lakha and Professor Richard Coker at the London School of Hygiene and Tropical Medicine worked with the Thai Ministry of Health.

They chose the best molecules to produce first in order to address Thailand’s health needs. As part of this process, datasets on breast cancer were generated, as well as a 10-year description of breast cancer epidemiology.

These resources could guide future policy decisions and highlight areas for research or development.

Upscaling protection against Dengue fever

Professor Mark Smales (Professor of Industrial Biotechnology at the University of Kent and co-investigator on the project) and his group collaborated with Dr Ramasoota (Mahidol University, Thailand). They were working to increase the yields of a monoclonal antibody for Dengue fever.

Dr Ramasoota and his group had previously developed the antibody; however, the yields of the protein were too low for commercialisation. Mark’s research group developed CHO cell lines that can express the antibodies 100-fold.

Dengue fever is a viral infection spread by mosquitoes, and severe Dengue is a major cause of illness across Asia and Latin America.

The World Health Organization estimates that half the world’s population is at risk for Dengue, although the majority of current infections are mild or asymptomatic. Climate change could increase the number of individuals affected by the disease, as well as expand the areas affected.

The cell lines and antibodies are now undergoing efficacy tests in Thailand to see if they prevent or treat Dengue fever in mice. If successful, the antibodies will be an effective therapy for those with Dengue fever, as well as alleviating the economic burden the disease causes.

Find out more

University of Kent, South East Asia Research Collaboration project

NBF website

Top image:  Credit: Jevtic, iStock, Getty Images Plus via Getty Images

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