🦟 A new dengue vaccine

Hello! Welcome to another edition of the Brazil Society newsletter! This week, we talk about the possibility of Brazil having its own vaccine against dengue fever — which has spread like never before in the country (and parts of South America) this year. 

You can reach me at [email protected] 

Butantan Institute seeks approval for dengue vaccine

The dengue outbreak in Brazil this year has shattered all previous records, with more than 5.8 million confirmed cases reported through November, according to the Health Ministry. The death toll, nearing 6,000, is also an unprecedented high, underscoring the devastating magnitude of the disease.

At the peak of the epidemic, in the first quarter of the year, multiple Brazilian states had to set up field hospitals to cope with the sheer number of dengue patients. And yet, demand for the two-jab dengue vaccine available in the public health care system has been underwhelming.

By September, less than half of the 4.8 million doses distributed to states were effectively used. Moreover, less than one-third of those who got the first jab returned for the booster shot.

But a new vaccine may help address these issues. The Butantan Institute, a biological research facility in São Paulo, this week submitted a request to Brazil’s health regulatory agency, Anvisa, to approve the Butantan-DV vaccine, a groundbreaking single-dose immunization candidate against dengue. If authorized, this would mark the first such vaccine in the world.

The formulation underwent trials starting in 2016, with the study concluding in June 2024. Over five years, researchers monitored more than 16,000 participants, of whom 10,300 received the Butantan-DV vaccine while the rest were given a placebo.

Results published in early 2024 in The New England Journal of Medicine revealed that the vaccine reduced the risk of dengue infection by 79.6%. A subsequent study, published in August in The Lancet Infectious Diseases, demonstrated sustained efficacy, with the vaccine lowering the risk of symptomatic dengue by 67.3% after nearly four years. Most notably, it reduced the risk of severe dengue or cases with warning signs by 89%.

The Butantan-DV vaccine offers protection against all four dengue virus serotypes transmitted by the Aedes aegypti mosquito. It uses an attenuated virus, which is capable of replication but unable to cause illness. The Butantan Institute developed the vaccine from a prototype created by Stephen Whitehead’s team at the US National Institutes of Health (NIH), a leader in vaccine research for insect-borne viruses.

Whitehead’s team genetically modified the dengue virus to reduce its virulence by removing a small segment of its genetic material, a technique effective for serotypes 1, 3 and 4. For serotype 2, researchers developed a hybrid virus combining the inner structure of serotype 4 with the outer structure of serotype 2. These four components were combined into a single vaccine formulation.

Building on the NIH prototype, Butantan enhanced virus production, improved purification and developed a freeze-dried version of the vaccine that remains stable at room temperature, unlike the original formulation requiring storage at -80 degrees Celsius (-112 degrees Fahrenheit).

The Brazilian development phase, including human trials, was funded by Fapesp, a research organization funded by the São Paulo state government, the National Development Bank (BNDES) and the Health Ministry.

“This is one of the greatest achievements in the history of Brazilian health and science, as well as a major international milestone. The Butantan Institute’s contribution to developing the first single-dose dengue vaccine underscores the importance of investing in homegrown research and innovation,” Esper Kallás, an infectious disease specialist and director of the Butantan Institute, said in a statement.

Anvisa will now evaluate the vaccine’s efficacy, safety, quality and manufacturing conditions. The agency had previously certified the Butantan-DV production facility in São Paulo’s Bioindustrial Center for good manufacturing practices. “We expect a swift response from Anvisa, as this is a smaller portion of the approval process,” said Gustavo Mendes, Butantan’s director of regulatory affairs, quality and clinical trials.

“I can't tell you when [the analysis of the demand will be processed],” said Antonio Barra Torres, the outgoing chair of Anvisa. “We’re talking about troves of documents in technical English that will require thorough evaluation. But rest assured that it will happen as soon as possible while ensuring that citizens’ health will be taken care of.”

If Anvisa approves the vaccine fully, the Butantan Institute will submit a pricing request to the Medicines Market Regulation Chamber (CMED), which assesses development costs and potential benefits to set market prices. The vaccine’s incorporation into Brazil’s SUS public health system will then be evaluated by the National Commission for Technology Incorporation (Conitec).

The Butantan Institute estimates it could supply up to 100 million doses of the Butantan-DV vaccine to the Health Ministry over the next three years, with 1 million doses available as early as 2025. Both individuals who have never contracted dengue and those previously infected would be eligible for vaccination. 

The Health Ministry will determine the immunization strategy upon approval.