The only dengue vaccine ever approved in the United States is being discontinued, raising questions about control of the mosquito-borne virus amid a decades-long surge in cases.
The vaccine, Dengvaxia, was approved by the FDA in 2019 for children aged 9 to 16 years living in U.S. territories where dengue is endemic, including American Samoa, Guam, Puerto Rico and the U.S. Virgin Islands.
Despite dengue's proliferation globally — WHO estimates that half of the world's population is at risk for infection — Sanofi Pasteur cited lack of demand when it announced that it would stop making the shot.
The remaining stock will expire next August, and because the vaccine is given in three shots over the course of a year, the time to start the series has come and gone.
The vaccine was designed to protect against all four serotypes of dengue. Natural infection with one serotype of dengue confers lifetime protection against that serotype but also raises a person's risk for serious illness if they are infected with one of the other three serotypes.
Similarly, because getting the vaccine could act as an initial infection, thus raising a person's risk for serious illness from a subsequent natural infection, children needed confirmation of a previous dengue infection before they were eligible to get Dengvaxia.
To get some perspective on the situation, we spoke with David Hamer, MD, co-core lead on climate change and emerging infectious diseases at Boston University's Center on Emerging Infectious Diseases, and Lyle R. Petersen, MD, MPH, FASTMH Healio | Infectious Disease News Editorial Board Member and director of the CDC's Division of Vector-Borne Diseases.
Healio: From our understanding the Dengvaxia stock expires next year which means anyone who wants or needs to get it needs to have already started the process since the vaccine is given as several doses over the span of a year Is this accurate?
Petersen: Existing lots of Dengvaxia have an expiration date of August 2026. The manufacturer will not produce additional lots. Therefore, given the 1-year-long vaccination series, no persons who have not already begun the series will be vaccinated.
Hamer Yes, but I think it's important to bear in mind that in the U.S., it was only approved for a narrow age range and for use in territories that are endemic for dengue, such as Puerto Rico. It was not approved for use in travelers and, so, this is the part where it becomes interesting.
There is another vaccine called TAK-003, branded Qdenga, that is a quadrivalent, live attenuated vaccine that has a better safety profile. It went through FDA review maybe 1 1/2 or 2 years ago, and it was not approved because of concerns that it didn't provide adequate protection against serotypes 3 and 4 — and particularly serotype 3 in people who had not had prior exposure to dengue serotype 4. They just didn't have enough data. And so globally, TAK-003 is being used very widely in Western Europe, Brazil and other endemic countries for control of dengue, and basically for protection of people in those countries and for protection of travelers. So, there is an alternative that has some limitations, but also has some strengths. It works very well for dengue serotypes 1 and 2, and one of the issues with Dengvaxia was that they basically limited its use to people who had evidence of having had dengue before by a lab test. So, you couldn't use it unless you could confirm that somebody had dengue at least once before. That's not the case with TAK-003 in most countries, unless some countries have made that requirement as well.
Healio: What happened with Dengvaxia and why is it being discontinued? Is it a public health messaging issue? Cost issue?
Hamer: What happened was a complicated story. It was approved and pre-qualified by WHO, and a couple of countries including Mexico and the Philippines began to scale it up. In the Philippines, they were continuing to do the follow-up of the original placebo-controlled trial and at 4 and 5 years after the initial vaccinations, they started to see an increase in hospitalizations and even a few deaths of young children with dengue who had received the vaccine. This led to a big public [outcry] because there were a lot of people saying, “Wait a minute, this vaccine might not be safe.” But what they showed is there's a phenomenon known as antibody dependent enhancement that people argue about. It basically suggests that you can get severe dengue if you have had it before, that you have antibodies to the virus but they're not strong enough to neutralize it if you're exposed to it again. Those antibodies then help facilitate greater uptake of the virus and more severe viremia, leading to more severe disease.
What they eventually showed was that for children in the original trial who were seronegative at baseline, the vaccine was equivalent to their first episode of dengue, but after a couple of years, they had waning protection from that. When they were exposed to dengue and got their second episode, they got really sick. The children in the original trial who had evidence at baseline that they'd had dengue before, the dengue vaccine was almost like a booster for them, and they did not have that happen.
Because of safety issues, they pulled back in the Philippines . Some countries had adopted it, but because they said you have to test for dengue seropositivity before you use it, it made it very inconvenient to implement. That led to a lot of loss of interest in this product. Eventually, because the market was so poor, Sanofi decided that it didn't make sense to continue producing it, and that's why we're at this point.
Petersen: Demand was certainly a major factor. At least in the U.S., the vaccine was only available for children aged 9 to 16 years living in an endemic area who had previous dengue infection. In practice, the vaccine was only available in Puerto Rico. The fact the vaccine required pre-vaccination antibody screening to determine if the child had previous dengue infection followed by a three-dose vaccine series made the vaccine unattractive. In Puerto Rico, despite a fairly robust public communication campaign, only a couple hundred children were vaccinated.
Healio: Why is there no public health awareness that this is happening?
Hamer: A lot of us know about it in the dengue world. I've known that this has been planned for over a year now, but I think the thing is the other vaccine, TAK-003, is actually recommended for children 6 to 16 years in settings of the high dengue disease burden, and has been authorized by the European Medicines Agency. This vaccine does not appear to have that problem associated with it that Dengvaxia had so, basically, there's no market for Dengvaxia and it's been replaced by Qdenga.
Petersen: I think there was little public awareness since the vaccine was only being administered to a very small segment of the U.S. population. Internationally, the Takeda vaccine is being marketed, which requires no prevaccination screening and is a two-dose series.
Healio: Does this mean there is no longer a dengue vaccine? If so, what does this mean for the dengue situation?
Hamer: Qdenga is not approved in the United States, but is available globally. There are also two other vaccines that are fairly far along. One is called the Butantan vaccine, and it's made by the Butantan Institute in Brazil. The other is made by Merck and is essentially the same vaccine.
The Butantan Institute has gone further and has actually done some phase 3 studies showing that the vaccine protects against virologically confirmed dengue for up to 4 years or so. Merck has its own set of studies going on its vaccine.
Our hope is that we will have a second dengue vaccine available within the next few years, in addition to Qdenga.
Petersen: There is no longer a dengue vaccine available in the U.S. The dengue situation is unchanged since very few people were vaccinated. The Takeda vaccine is available in an increasing number of countries worldwide.
Healio: What i s being done to cut dengue transmission?
Hamer: Not enough is the short answer. But the reality is dengue, particularly in 2024 , just exploded. I think it's a combination of the warming climate, but also, more cycles associated with El Niño, with sea surface temperatures and rainfall patterns.
Dengue has been really expanding worldwide . The presence of competent vectors that can transmit are much more widespread, both in low- and middle-income countries in Southeast Asia, South Asia and Latin America, but also increasingly in Sub-Saharan Africa. In fact, there have been some substantial outbreaks of dengue in the last 2 years. So, dengue is expanding.
There are efforts to try and improve dengue control that range from the use of natural larvicides that destroy the larva to standing water control and trying to drain water reservoirs where the mosquitoes — the Aedes aegypti — can breed.
There are also really innovative approaches with genetically engineered mosquitoes . The ones that have gone the furthest are those that worked on introducing a bacteria called Wolbachia
References:
Announcement regarding the definitive discontinuation of the manufacture/import of the drug Dengvaxia (dengue 1, 2, 3 and 4 vaccine, recombinant and attenuated). https://www.sanofi.com.br/pt/noticias/informacoes-de-produtos/2025-2-28-comunicado-sobre-a-descontinuacao-definitiva-da-fabricacao-importacao-do-medicamento-dengvaxia-vacina-dengue-1-2-3-e-4-recombinante-e-atenuada . Published Feb. 28, 2025. Accessed Sept. 16, 2025.
CDC. About a dengue vaccine. https://www.cdc.gov/dengue/vaccine/index.html/ . Updated May 15, 2025. Accessed Sept. 15, 2025.
WHO. Dengue. https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue . Updated Aug. 21, 2025. Accessed Sept. 16, 2025.
For more information
David Hamer, MD can be reached at dhamer@bu.edu
Lyle R. Petersen, MD, MPH, FASTMH can be reached at lxp2@cdc.gov
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Source:
Healio Interviews
Disclosures: Hamer reports receiving research funding from Merck and Sanofi and receiving research funding and serving as an advisor for Takeda. Petersen reports no relevant financial disclosures.