Dengue vaccine pioneer in search of salvation

Dengue vaccine pioneer in search of salvation

Mahidol University has licensed dengue vaccines to France, Japan and India, but no one locally

Prof Emeritus Dr Sutee Yoksan, advisor of the Center for Vaccine Development, Mahidol University. Photo by Mahidol University
Prof Emeritus Dr Sutee Yoksan, advisor of the Center for Vaccine Development, Mahidol University. Photo by Mahidol University

It is a combination of boundless scientific curiosity and an unflagging desire to save lives that has kept Prof Emeritus Dr Sutee Yoksan, 72, working on research and development of vaccines against mosquito-borne diseases for more than 40 years.

He is widely known as a leader in research on dengue and other arthropod-borne viral diseases in Thailand. He also has published more than 100 papers in international peer-reviewed scientific journals, contributed to books and written review articles.

Among his several awards is a Mahidol Distinguished Researcher Award in 2006 and the Excellence Award for medical virology bestowed by the Asia-Pacific Society of Medical Virology in 2009.

Born in Trang in 1949, Dr Sutee graduated from Mahidol University with a doctorate in 1974. He trained in clinical pathology at Ramathibodi Hospital School of Medicine for two years and spent another two years training in flavivirology at the University of Hawaii in the United States and Oxford University in the UK. He graduated with a doctorate in science from Mahidol University.

He joined the Centre for Vaccine Development of the university in 1987 and became its director in 1989, serving until he retired. Today he is the centre's adviser. Under his leadership, the research team developed vaccines against dengue viruses and vaccine candidates against Japanese encephalitis in addition to the Zika and chikungunya viruses.

Mahidol University also licensed its dengue vaccines to several vaccine manufacturers in France, Japan and India.

"Our dengue vaccine does not require boosters. Within one shot, the vaccine can fight all four serotypes of the dengue virus. The immunity can last five to eight years and the efficacy is 100%," he told the Bangkok Post.

He hopes that eventually one of the local vaccine manufacturers, which are focused on developing Covid-19 vaccines, will be interested in producing a locally developed dengue vaccine.

Mahidol University does not have the capacity to produce the vaccine on an industrial scale, for which big investment is needed. Dr Sutee and his team can produce the prototype and transfer the knowledge to a company able to do so, like the GPO.

Why the interest in developing a dengue vaccine?

Dengue is a mosquito-borne virus. The virus has four strains, DENV-1 to DENV-4. If someone is infected by one strain, he or she can get sick with other strains so it is important to have a vaccine that can protect us from the four dengue serotypes.

In 1977, the World Health Organization (WHO) Regional Office for Southeast Asia proposed a project for dengue vaccine research. It selected the Department of Pathology, Faculty of Medicine of Mahidol University as its partner.

Prof Natth Bhamarapravati, the then rector, founded the Center for Vaccine Development (CVD) to undertake dengue vaccine research and development. I joined the team because I knew that having a vaccine against dengue viruses was crucial to preventing people from getting sick. It is meaningful work for me.

When did the project start?

The vaccine project started in 1980. It was a joint effort between the government and Mahidol University and also partly funded by the WHO regional office, the Rockefeller Foundation and the Italian government. Our vaccine was a live attenuated tetravalent dengue vaccine. We use the serial passage technique [originally developed by Louis Pasteur in the 1880s for producing an early rabies vaccine]. The virus attenuation technique is the best strategy and most effective way to obtain the vaccine against dengue viruses.

During our first 12 years of operation, WHO sent its international panel of experts to monitor our work. They reviewed the progress we made and followed up with peer review meetings. They also gave us and the Public Health Ministry recommendations to make sure that our R&D was up to an international standard.

What happened after you developed the first dengue vaccine?

In the early 90s, we could not find any manufacturers in Thailand that could produce live attenuated dengue vaccine technology. In 1993, Mahidol University signed an agreement with Pasteur Merieux [now Sanofi Pasteur] in France, to license the vaccine, and gave the company full rights to develop the tetravalent dengue vaccine, while Mahidol provided technology transfer.

From 2005–2010, we developed a second-generation dengue vaccine to improve its efficacy. It was also a single-shot vaccine. At that time, not a single organisation in Thailand paid attention to investing in our vaccine for commercial use. In 2011, we licensed the vaccine to Kaketsuken [now Kumamoto Meiji Biologics or KMB] in Japan. KMB has an agreement to produce dengue vaccines for sale to developed countries.

In 2013, Mahidol University signed another contract with the Serum Institute of India [the world's largest vaccine manufacturer], allowing the company to develop and sell the vaccine to developing countries. However, the firm later cancelled the agreement due to outside influence [by an international organisation Dr Sutee asked not to be named].

Why don't you offer the production licence to a local firm?

I have presented our dengue vaccine to various state agencies in Thailand over the past 40 years. They have listened to my presentations but nothing ever happened. None of them wanted to commit to a substantial investment for manufacturing the vaccine. We need a visionary person who foresees that if we produce our own dengue vaccine, Thailand can be a vaccine hub for the region. If we do not start now, we will keep buying vaccines from abroad.

It is sad to learn that companies in other countries see the benefits of our dengue vaccine. They invested in our technology but not a single company in Thailand has done so.

Now that a licence to produce dengue vaccines for developing countries is available, this is a good opportunity for vaccine manufacturers in Thailand to grab the licence for production. They can also distribute dengue vaccines to other developing countries. Dengue vaccine is needed not only in Thailand but also in neighbouring countries in Asia and around the world.

Who needs to be inoculated?

Dengue vaccine is recommended for adults at least 20 years old. They should get one shot. Our single shot can prevent four dengue strains and the immunity can last a long time. The vaccine is not recommended for kids and young adults between 2-19 years old because they're less likely to have experienced a possible dengue infection, which sometimes does not have any symptoms or has only mild symptoms. If they need to get the dengue vaccine, they must have a blood test before being inoculated. The vaccine should not be administered to pregnant women or breastfeeding mothers.

How serious is the dengue situation nowadays?

In the past five years, the number of people infected with the dengue virus in Thailand has varied between 50,000 and 100,000 cases per year. The number of deaths is 50-123 people a year. The ratio of deaths is 1:1,000 people. Although infections are not as high as for Covid-19, people die because of the dengue virus every year.

At present, there is no specific medication for curing dengue disease. A doctor will prescribe medicine based on a patient's symptoms. Some may have severe conditions so it is better to prevent than cure.

Apart from a licence for manufacturing dengue vaccines, are there any other types of vaccine licences against mosquito-borne diseases that Mahidol offers?

Our Center for Vaccine Development is a WHO-approved reference laboratory on serology and virology for dengue and Japanese encephalitis [JE] viruses. We have also developed the JE vaccine. In 2017, we signed a contract with the Government Pharmaceutical Organisation to further develop the vaccine for mass production. We expect the vaccine to be released soon.

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