Dr. Capeding led the first Phase 3 trial ever completed for a dengue vaccine candidate. The results of this trial in Asia (involving Sanofi Pasteur’s dengue vaccine candidate) were published this summer, July 11, in The Lancet. This exclusive interview, originally published by the Dengue Vaccine Initiative (DVI), captures her thoughts about dengue and the trial.

 

Can you briefly tell us about yourself, your scientific career?

I am a practicing pediatrician with subspecialty in infectious diseases and the Head of the Department of Dengue at the Research Institute for Tropical Medicine, the research arm of the Department of Health and referral center for infectious diseases in my country, the Philippines. I'm also the head of the Department of Microbiology.

How did you get involved with dengue?

Dengue is endemic in my country. It is one of the most prevalent factors behind the high number of hospitalization here. 

I also had a personal connection to dengue. My son got infected with dengue when he was a medical student. As a mother, this was one of my worst experiences and I can identify with the pain of dengue and the burden of the disease for many others. One of the worst things about my son being sick with dengue was the uncertainty of what would happen during that time. You really don't know what's going to happen. Was he going to go into shock? Was he going to bleed? He did end up with dengue hemorrhagic fever. He started getting low blood pressure and I was extremely anxious and worried. The worst of this disease is its unpredictability. This causes much burden. 

I have also had colleagues, other doctors, who have contracted dengue and they seriously thought that they were going to die. The pain is agonizing and you just don't know how bad it will get.

How would you convey the global burden of dengue? How is it a global public health threat, given its low mortality rate relative to diseases like malaria?

Dengue is a major international public health concern. There is no specific treatment or effective prevention measures for dengue. It's a health priority in many countries of Latin America and Asia where epidemics occur regularly, but, also look at Japan… In recent weeks it had a case of dengue after 60 years of being free of this disease.

What are the major complexities of dengue challenging the R&D of a vaccine to prevent this disease? 

I would mention three: (1) the 4 serotypes of dengue virus, requiring a vaccine that must protect against all four, in other words, a vaccine that is tetravalent; (2) the lack of an animal model; and, (3) the theoretical risk of imunopotentiation, that is, a patient who got infected more than once may develop more severe manifestations of dengue, hence there’s the need for a large scale clinical trials.

How do you see the future of dengue worldwide? 

I think we have a working vaccine. I'm quite pleased with the results and the future of dengue will hopefully involve a combination of the use of this vaccine with existing vector-control strategies. I do believe that countries must continue their vector control strategies to control dengue and complement the use of the vaccine.

What are the implications of this trial for the dengue research community?

Researchers worldwide have been working on a dengue vaccine for more than 60 years and for the first time we have a potential candidate that shows great promise. This takes us closer to bringing a first vaccine against dengue to the world. 

How would you explain the variability of protection against each serotype observed for this candidate? How would it affect the benefits of the use of this vaccine in different dengue-endemic countries?

Serotype 2 has been a challenge, but the prerelease of the findings from the CYD15 (the Sanofi Phase 3 second trial, which took place in Latin America) shows that the vaccine can prevent against it. 

We must remember that the 4 serotypes circulate and one serotype may be predominant during this season and another during the next, but, still, they co-circulate. And this vaccine protects against all 4 serotypes. I am sure the research program on dengue continues, at the moment we must focus on the dengue chimeric vaccine to become the world's first vaccine against this disease.

Being in different areas, though, and with different age groups and regional characteristics, how do you view these trials together? How do you compare them?  

The important thing to point out here is the consistency of the results. The Latin American results are consistent with what we found in Asia. Both studies met their primary clinical endpoint with significant findings on reduction of dengue severe disease and reduction in the number of hospitalizations.

How can you extrapolate these findings to other regions and countries, like Africa, India, and China?

Both CYD14 and CYD15 provide further evidence of this candidate’s impact on protecting those at risk from dengue in a broad population and in various epidemiological environments.  Likewise, we have comprehensive data from clinical trials conducted in fifteen countries involving 40000 children, adolescents and adults.  

Now that the results are published, how do they affect the decision to use this vaccine? What are the next steps? What questions do you consider to be crucial for the community and public health officials to ask themselves before this vaccine is introduced?

It is important to consider the vaccine efficacy rate and the results from both Asia and Latin America bolster the evidence of the vaccine's efficacy and safety and the impact they could have in protecting those at risk from dengue especially in dengue-endemic countries. 

One must consider the safety data from the numerous clinical trials and no safety signal to date; this will be the basis for submissions to the health authorities in countries where dengue is a public health priority.  We have a vaccine with good safety profile, safety data reviewed by an Independent Data Management Committee (IDMC) for any safety signals.  

What has excited you the most, personally, about leading this trial?

I am very pleased with the results from the efficacy study, as a resident in a country where dengue is a major public health problem, as a clinician who takes care of the health of children and as a mother whose biggest nightmare was having a son sick with dengue. 

I look forward to having the world's first vaccine against dengue become a reality. I am truly happy.