The story behind the new dengue vaccine
23 August 2022 update: Takeda’s tetravalent dengue vaccine (TAK-003) receives first global approval for use in Indonesia without need for pre-vaccination testing. Read the press release.
In June, Takeda Pharmaceutical Company Limited presented results from trials of its dengue vaccine candidate. The vaccine, TAK-003, had a protective efficacy of 62% against development of symptomatic dengue disease and 84% against hospitalisation. No important safety risks were identified in the overall population.
We spoke with Prof Emeritus Dr. Sutee Yoksan, Advisor of the Center for Vaccine Development, Mahidol University, Thailand, whose research is behind the vaccine to find out more about the development of this vaccine.
We asked Professor Yoksan for a little information about dengue fever.
Prof Sutee Yoksan: Dengue is part of a family of viruses including yellow fever, west nile virus and encephalitis, and there are four strains: Dengue 1-4. It is prevalent in tropical and sub-tropical regions of the world and transmitted by mosquitoes.
In the last two decades the number of dengue cases reported to WHO has increased from around 0.5 million in 2000 to 5.2 million in 2019 and deaths have increased from 960 in 2000 to 4032 in 2015.* The number of countries where dengue is transmitted are also on the rise.
Because there are four variants, even after dengue infection people have antibodies only for the strain they have encountered, with only transient immunity for the others.
We asked about the history of dengue vaccine development at Mahidol University prior to industrial development at Takeda.
Prof Sutee Yoksan: In 1980 I was leader of the dengue vaccine development program at Mahidol University, and we started a collaboration with the University of Hawaii, USA. We were using a method whereby the virus is grown in iterations in non-human cell types and studying the results. The aim is to develop a weakened virus that will provoke an immune response without making people sick.
In the process, we compared the original and subsequent - progeny - variances and developed potential vaccines of all four dengue strains. The next challenge was to find a way to stimulate the immune to mount a response to all four strains in one vaccine.
In the 1990s, Mahidol University signed a Cooperation Research and Development Agreement with the US Centers for Disease Control and Prevention and our focus was on creating a vaccine that would protect against all four strains.
Phase 1 clinical trials were carried out for the vaccines for dengue 1, 2 and 4, and then we moved to work with the vaccine we had developed for dengue 2, but added certain key genes from the other three strains. You can think of this as having the backbone of a dengue 2 virus with immunogenic elements of the others in the mix. In this way, the immune mounts an antibody response against all four dengue variants.
What advice would you give other researchers who want to commercialise research?
Prof Sutee Yoksan: There are multiple pathogenic mechanisms involved in dengue, which makes it difficult to establish suitable vaccines. In my experience, scientists must be engaged in working in a laboratory for many years in search of new knowledge and clear insights. They also have to learn what to pursue and when to stop their experiments.
Research relies on collaboration and cooperation networks at an international level to move the innovation from laboratory to industry. After several decades of working in the field, I would say that working only at the national level was not enough.
To create these opportunities, you need to work hard to build a network; try to communicate with the right people, publish and share your results with others.
What motivates you to keep going in your research?
Prof Sutee Yoksan: Several findings in science have highlighted knowledge gaps worth pursuing. The beauty of science could inspire a lot of people, including myself, to go into research, but along the way there have been many people who were willing to guide and help me stay on track. This has been really important, as there have been times when the research has been very challenging or a particular avenue has dried up and we wonder if we are going in the right direction.
What motivated you to research mosquito-borne diseases?
Prof Sutee Yoksan: Mosquitoes have a prominent role in transmitting many RNA viruses including Dengue, Chikungunya, Zika and Japanese encephalitis viruses. The population at risk has been increasing as mosquitoes spread into more and more countries. In Thailand alone there are between 25,000 and 100,000 cases of dengue each year and many more cases of other diseases that are transmitted by mosquitoes.
Mosquito control is extremely difficult to achieve and sustain. I believe vaccine research is the most appropriate approach to protect people. With present technologies and contributions from scientists around the world vaccine innovations will be accelerated. And with success people can get on with their life without worrying about mosquito bites.
How important is communication?
Prof Sutee Yoksan: Communication is of highest priority for all levels, from funding agencies to policy decision-making in vaccine introduction. There are several factors that lead to success or failure at national programmes: we have to provide clear results of our findings at scientific meetings - scientific data will help to provide our partners with suitable strategic plans to reduce dengue morbidity, mortality and its negative socio-economic impact. In addition, we have to communicate with a lot of people to find the right ones to work with. Discipline is required in ensuring we work with diverse groups of people, and this means working hard to communicate.
What’s next for the vaccine?
Prof Sutee Yoksan: Vaccines offer the greatest hope for dengue prevention and control. In our national program, we are working on a demonstration project to introduce the vaccine to people in small regions.
Monitoring will be important. If someone develops a fever, we need to be quick to diagnose and check what it is. We need to work with local groups and local authorities and ensure they also communicate the benefits to the media. It will be important to have a slow rollout and be very careful with potential side effects to build trust as we go.
Finally, we hope people of all ages will benefit and be protected from dengue, perform their daily activities as needed and enjoy life.
Read the press releases from Takeda Pharmaceuticals
- Takeda’s Dengue Vaccine Candidate Provides Continued Protection Against Dengue Fever Through 4.5 Years in Pivotal Clinical Trial
- Takeda’s tetravalent dengue vaccine (TAK-003) receives first global approval for use in Indonesia without need for pre-vaccination testing
Read the papers related to the TAK-003 Dengue vaccine
- Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents
- Genetic and Phenotypic Characterization of Manufacturing Seeds for a Tetravalent Dengue Vaccine (DENVax)
- Three-year Efficacy and Safety of Takeda’s Dengue Vaccine Candidate (TAK-003)